Dietary supplementation with seeds of Sesamum indicum L. (pedaliaceae) mitigates the 7,12-dimethylbenz(a)anthracene-induced breast tumor burden in rats.

OBJECTIVES: Sesamum indicum L. seeds; rich in zinc and lignans are endowed with antioxidant and immunomodulatory properties which attract research on their anticancer potential. Although many studies have reported the in vitro antitumor potential of S. indicum and its phytoconstituents, much is yet to be known about its in vivo effects. To fill this gap, the effects of dietary supplementation with seeds of S. indicum in 7,12-dimethylbenz(a)anthracene-exposed rats was assessed. METHODS: 42 rats aged 30-35 days were randomized into six groups (n=6) as follows: the normal (NOR) and negative (DMBA) control groups were fed with standard diet; the positive control group (DMBA + Zinc) was fed with standard diet supplemented with commercial zinc (0.01 %); the test groups were fed with standard diet supplemented with S. indicum seeds in different proportions (6.25 , 12.5 and 25 %). Breast cancer was induced by a single administration of DMBA (50 mg/kg BW, s.c.) diluted in corn oil. The experiment lasted 20 weeks and afterward, tumor incidence; tumor burden, tumor volume, tumor micro-architecture and some biochemical parameters were evaluated. RESULTS: As salient result, 100 % of rats in the DMBA group developed tumors, while rats feed with rat chow supplemented with S. indicum seeds (25 %) had a reduced incidence of tumors (33.3 %) and tumor volume (2.71 cm3 in sesame 25 % vs. 4.69 cm3 in the DMBA group, p˂0.01). The seeds (25 %) also slowed DMBA-induced neoplasm expansion in mammary ducts as compared to rats of DMBA group. CONCLUSIONS: In summary, supplementation with S. indicum seeds slowed breast tumorigenesis via its antioxidant capacity.

Chemical profiling, bio-guided purification, and cytotoxic effect of two African spices: Hypodaphnis zenkeri Engl. Stapf (Lauraceae) and Staudtia kamerunensis warb (Myristicaceae) on human prostate cancer cell lines.

ETHNOPHARMACOLOGICAL RELEVANCE: Prostate cancer remains a significant burden in low- and middle-income countries and the second leading cause of death around the world. Spices used in daily cuisine contain interesting phytochemical components capable of helping prevent and cure cancer. AIM: This study aims to give sufficient phytochemical information on two understudied species, Staudtia kamerunensis Warb. (Myristicaceae) and Hypodaphnis zenkeri Engl. Stapf. (Lauraceae), and to study their cytotoxicity against prostate cancer cells in its early form and when they have developed metastasis. MATERIALS AND METHODS: To reach this goal, normal procedures for phytochemical analysis were followed; these include collection, drying, crushing and extraction of plant materials using organic solvents. GC-MS (Gas chromatography- Mass Spectrometry) was used to evaluate the volatile phytochemicals contained in the extracts, and opened-column chromatography was used to isolate the pure compounds used in this study. A bio-guided exploration of Hypodaphnis zenkeri (Lauraceae) (leaves, seeds, stems) guided us in selecting the extract for further analysis. An established MTT assay was used to measure cell proliferation. Three prostate cancer cell lines were considered in this study, DU145 and PC3, human androgens-independent prostate carcinoma cells and LNCaP, which are cells derived from metastasis of a human prostate and respond to androgens, oestrogens and progestins. The eight compounds isolated were characterized using HREIMS, 1D and 2D NMR. RESULTS: Among the three extracts from Hypodaphnis zenkeri, considered for biological testing, the leaf extract displayed better activities with a CC50 of 180 µg/mL against DU 145 cells, 184 µg/mL against PC3 cells and 194 µg/mL against LNCaP cells. These results were justified when GC-MS analysis of the different extracts was performed. Fifty compounds were identified from the leaves, representing 96.06% of the volatile components, with most displaying anticancer activities or activities against vectors favourising cancer growth (inflammation, etc.). An attempt to isolate the active principle responsible for the cancer activity led to the isolation of five pure compounds, namely Eicosane [1], Nonacos-1-ene [2], Palmitic acid [3], Glucoside Stigmasterol [4] and Butane-1,2,3,4-tetraol [5]. Eicosane was identified as being responsible in part for the observed activity, even though it exhibited weak cytotoxicity with the lowest CC50 equal to 30 µg/mL against DU 145 cells. Staudtia kamerunensis sap was investigated in our previous studies with the isolation of Oleanan-12-ene-2α,3ß -diol [6] and 2α, 3ß -dihydroxylup-20-ene [7] among the major components, with significant antibacterial properties. Oleanan-12-ene-2α,3ß -diol [7] in this study displayed a CC50 of 20 µg/mL against DU145 cells, 22 µg/mL against PC3 cells, 18 µg/mL against LNCaP cells, and 32 µg/mL in HMEC affording a selectivity index >2. Contrary to what was observed in our previous study, the activity of Oleanan-12-ene-2α,3ß -diol was lost in the presence of 2α, 3ß -dihydroxylup-20-ene. CONCLUSION: the cytotoxic effect of extract from Staudtia and Hypodaphnis genera and pure isolates are here reported for the first time, as long as the pure isolates. These studies exhibit the cytotoxic potential of two traditional African spices and, more specifically, Oleanan-12-ene-2α,3ß -diol and eicosane, isolated from these plant species.

Duguetia confinis Engl. & Diels (Annonaceae) inhibitory and cytotoxic effects on breast adenocarcinoma growth both in vitro and in vivo.

Background: Breast cancer is ranked as the most common malignant tumor in women globally with ∼ 2.3 million new cases (11.7 %) diagnosed in 2020. The multiple drawbacks associated with treatments, prompt researchers and patients to search for alternative therapy. Plants continue to offer encouraging leads, in particular those of the Annonaceae family, to which belongs Duguetia confinis, used by Cameroonian traditional healers to fight cancers. This study was aimed at investigating the effect of Duguetia confinis against human breast cancer cells. This was carried out by investigating the cytotoxicity, underlying mechanism of action and chemopreventive potential of D. confinis on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer. Methods: To achieve this goal, the ethanolic extract of the bark of D. confinis was prepared and assayed for its ability to inhibit cell growth, cell proliferation and clone formation. Furthermore, cell death mechanisms, cell cycle progression and anti-metastatic potential were investigated. The in vivo study consisted in a once-off administration of 50 mg/kg BW DMBA (in olive oil, s.c) from the 10th day after pretreatment with D. confinis extract (50 and 100 mg/kg BW) or standards [tamoxifen (3.3 mg/kg) and letrozole (1 mg/kg)] or leaf extract of Annona muricata L. (200 mg/kg as pharmacological control). Normal and negative controls received vehicle (3 % ethanol). The treatment of animals was done for 20 weeks, followed by the assessment of the incidence, burden and volume of tumors, breast cancer biomarker (CA 15-3), antioxidant status, inflammatory status and histopathology profile. The LD50 of D. confinis extract was estimated according to OECD guideline 423. Results: D. confinis displayed cytotoxicity at 80 µg/mL on all the tested breast cancer cell lines. It induced apoptosis and caused a blockade at G0/G1; S-phase of MDA-MB 231 cells, thus, suggesting anticancer potential. A significant concentration-dependent antimetastatic potential was observed with D. confinis extract at 50 (p < 0.05) and 100 (p < 0.01) µg/mL, evidenced by a reduction in cell migration, chemotaxis and increased adhesion to extracellular matrix. With respect to the chemopreventive study, D. confinis was able to prevent the onset of breast adenocarcinoma in Wistar rats by preventing the growth of tumor mass and volume, as well as the histopathological severity of the disease. This was achieved through the modulation of antioxidant parameters (SOD, CAT, MDA) and inflammatory parameters (IL-12, IL-6, INF- gamma, TNF). Also, the LD50 of D. confinis extract was greater than 2000 mg/kg, indicating low acute toxicity and thus, favorable for therapeutic use. Conclusion: In summary, this study outlines for the first time the beneficial effect of D. confinis as a plant candidate in the fight against breast cancer just like other species of the Annonaceae family. However, further research studies are still warranted regarding its bioactive components, and in depth investigation of its anticancer mechanism of action are also needed.

Aridanin and oleanane-3- O-ß-D-glucoside-2'-acetamide obtained from Tetrapleura tetraptera (Schumach. & Thonn) Taub. (Fabaceae) induces potent apoptotic activity in human prostate cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrapleura tetraptera (Schumach. and Thonn.) Taub. (Fabaceae) is a tropical plant that is used in Cameroon pharmacopeia for the treatment of many cancers including prostate cancer (PCa), which is a major cause of men's death worldwide. The objective of this study was to evaluate the anticancer properties as well as underlying mechanisms of isolates from T. tetraptera on DU145, PC3 and LNCaP cancer cell lines. MATERIALS AND METHODS: Eight (8) compounds were purified from T. tetraptera stem bark extract through silica gel column chromatography (CC) and characterized using spectroscopic techniques (1D and 2D NMR), HRESIMS. Cell growth was assessed by a well-characterized MTT assay, while BrdU and clonogenicity assays provided information on the cell proliferation index. Further, the impact of the compounds on cell cycle progression and cell death were performed through Flow cytometry. Cell adhesion, cell migration and chemotaxis along with some proteins of epithelial-mesenchymal transition (EMT) were assayed. RESULTS: Out of the eight (1-8) isolates from T. tetraptera only oleanane-3-O-ß-D-glucoside-2'-acetamide and aridanin showed potent cell growth arrest with an estimated CC50 of 15, 23, 16 and 17, 26, 16 µg/mL on DU145, PC3 and LNCaP cells, respectively. A 15% (DU145) and 25% (LNCaP) increase in apoptotic cells induced by oleanane-3-O-ß-D-glucoside-2'-acetamide and aridanin at 10 µg/mL were noticed. Oleanane-3-O-ß-D-glucoside-2'-acetamide and aridanin at 2.5 and 10 µg/mL reduced the number of cells in S-phase and raised cells in G2/M phase. At the same concentrations, they decreased the number of invading DU145 cells and increased the adherence of DU145 cells to fibronectin and collagen matrix at tested concentrations, accompanied by an increase in integrin ß-1 (10 µg/mL) and integrin ß-4 (2.5 µg/mL) expression. Furthermore, a down-regulation of pcdk1, cdk2, Bcl-2, N-Cad, vimentin and cytokeratine 8-18 was noticed while, p19, p27, p53 pAKT, Bax, caspase-3 and E-Cad were up-regulated. CONCLUSIONS: This study outlines for the first time, the anticancer ability of compounds oleanane-3-O-ß-D-glucoside-2'-acetamide (4) and aridanin (6) from Tetrapleura tetraptera and proposes their putative mechanisms of action.

Comparative anticancer effects of Annona muricata Linn (Annonaceae) leaves and fruits on DMBA-induced breast cancer in female rats.

BACKGROUND: Numerous studies have reported the anti-cancer effects of different parts of Annona muricata Linn, however ; most of them focused on the in vitro evaluation of isolates. In vivo evidence on which part is best suited for breast cancer chemoprevention remains to be demonstrated. This is a comparative study of the effects of A. muricata fruit and leaves extracts on DMBA induced-breast cancer in rats. METHODS: Rats exposed to DMBA (50 mg/kg, s.c.), were treated with A. muricata fruit aqueous extract at 200 mg/kg BW (3 days/week or daily) and A. muricata Linn leaves ethanolic extract at 200 mg/kg daily. Positive control group received tamoxifen at 3.3 mg/kg, while the normal and diseased controls received vehicle. After 20 weeks of treatment, the tumor incidence, tumor burden, tumor volume, histopathology, protein and CA 15 - 3 levels as well as antioxidant status, pro-inflammatory cytokines were assessed. RESULTS: Thus, 100% of diseased rats presented cribriform ductal carcinoma of SBR grade III. A. muricata extracts (leaves and fruit) and tamoxifen significantly reduced death and tumor incidences, volume and weight of the tumors, total protein and CA15-3 levels compared to the DMBA group. They exhibited antioxidant activity, through an increase in the GSH level and SOD and catalase activities with reduced levels of MDA compared to DMBA group. TNF-α, IL-6 and INF-γ levels reduced with regards to A. muricata treatment. CONCLUSION: These results confirm the anti-breast cancer effect of A. muricata, however, the aqueous fruit extract was more potent than the ethanolic leaves extract.

Cucumis sativus (Cucurbitaceae) seed oil prevents benzo(a)pyrene-induced prostate cancer in vitro and in vivo.

Despite enormous progress in modern medicine, prostate cancer (PCa) remains a major public health problem due to its high incidence and mortality. Although studies have shown in vitro antitumor effects of cucurbitacins from Cucumis sativus, the in vivo anticancer effect of the seed oil as a whole, has yet to be demonstrated. The present study evaluated the in vitro anticancer mechanisms of C. sativus (CS) seed oil and its possible chemopreventive potential on benzo(a)pyrene (BaP)-induced PCa in Wistar rat. In vitro cell growth, clone formation, cell death mechanism, cell adhesion and migration as well as expression of integrins ß-1 and ß-4 were assessed. In vivo PCa was induced in 56 male rats versus 8 normal control rats, randomized in normal (NOR) and negative (BaP) control groups which, received distilled water; the positive control group (Caso) was treated with casodex (13.5 mg/kg BW). One group received the total seed extract at the dose of 500 mg/kg BW; while the remaining three groups were treated with CS seed oil at 42.5, 85, and 170 mg/kg BW. The endpoints were: morphologically (prostate tumor weight and volume), biochemically (total protein, prostate specific antigen (PSA), oxidative stress markers such as MDA, GSH, catalase, and SOD) and histologically. As results, CS seed oil significantly and concentration-dependently reduced the DU145 prostate cancer cell growth and clone formation (optimum = 100 µg/mL). It slightly increased the number of apoptotic cells and inhibited the migration and invasion of DU145 cells, while it decreased their adhesion to immobilized collagen and fibrinogen. The expression of integrin ß-1 and ß-4 was increased in presence of 100 µg/mL CS oil. In vivo, the BaP significantly elevated the incidence of PC tumors (75%), the total protein and PSA levels, pro-inflammatory cytokines (TNF-α, IL-1, and IL-6) and MDA levels compared to NOR. CS seeds oil significantly counteracted the effect of BaP by decreasing significantly the PC incidence (12.5%), and increasing the level of antioxidant (SOD, GSH, and catalase) and anti-inflammatory cytokine IL-10 in serum. While in BaP group PCa adenocarninoma was the most representative neoplasm, rats treated with 85 and 170 mg/kg prevented it in the light of the casodex. It is conclude that CS may provide tumor suppressive effects in vitro and in vivo which makes it an interesting candidate to support the current treatment protocol.

Breast cancer cell growth arrest and chemopreventive effects of Passiflora edulis Sims (Passifloraceae) ethanolic leaves extract on a rat model of mammary carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Despite various prevention and treatment measures, the incidence and mortality due to breast cancer has been increasing globally. Passiflora edulis Sims is a plant used for the treatment of various diseases in traditional medicine, including cancers. AIM OF THE STUDY: To assess the anti-breast cancer activity of the ethanolic extract of P. edulis leaves in vitro and in vivo. MATERIAL AND METHODS: In vitro, the cell growth and proliferation were determined based on the MTT and BrdU assays. The flow cytometry was used to analyze the cell death mechanism while, cell migration, cell adhesion and chemotaxis were assayed for anti-metastatic potential. In vivo, 56 female Wistar rats aged 45-50 days (∼75 g) were exposed to 7,12-dimethylbenz(a)anthracene-DMBA except the normal group. Negative control group (DMBA) received solvent dilution throughout the study; standards groups (tamoxifen - 3.3 mg/kg BW and letrozole - 1 mg/kg BW) as well as P. edulis leaves ethanolic extract groups (50, 100 and 200 mg/kg) treated for 20 weeks. Tumor incidence, tumor burden and volume, CA 15-3 serum' level, antioxidant, inflammatory status and histopathology were assessed. RESULTS: P. edulis extract showed a significant and concentration-dependent inhibition of MCF-7 and MDA-MB 231 cells growth at 100 µg/mL. It inhibited cell proliferation and clones' formation and induced apoptosis in MDA-MB 231 cells. The migration of cell into the zone freed of cells and the number of invading cells after the 48 and 72 h were significantly diminished while, it increased their adherence to collagen and fibronectin extracellular matrix as does Doxorubicin. In vivo, all rats in the DMBA group exhibited a significant (p < 0.001) increase in tumor volume, tumor burden and grade (adenocarcinoma of SBR III) and pro-inflammatory cytokine levels (TNF-α, INF-γ, IL-6 and IL-12). P. edulis extract at all tested doses significantly inhibited the DMBA-induced increase in tumor incidence, tumor burden and grade (SBR I) as well as pro-inflammatory cytokines. Moreover, it increased enzymatic and non-enzymatic antioxidants (SOD, catalase, and GSH) and decreased MDA levels although a greater effect was observed with Tamoxifen and Letrozole. P. edulis has medium content on polyphenols, flavonoids and tannins. CONCLUSION: P. edulis has chemo-preventive effects against DMBA-induced breast cancer in rats probably through its antioxidative, anti-inflammatory and apoptosis-inducing potentials.

Estrogenic and anti-amnesic potential of Millettia griffoniana Baill. (Fabaceae) ethanolic extract on scopolamine-induced memory impairment in ovariectomized Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dementias including Alzheimer disease (AD) are three times higher in menopausal women than in men. Phytoestrogens, a group of plant-derived compounds are known to alleviate menopausal complaints including dementia. Millettia griffoniana Baill is a phytoestrogen-rich plant used to treat menopausal complaints and dementia. AIM: Evaluating the estrogenic and neuroprotective potential of Millettia griffoniana on ovariectomized (OVX) rats. MATERIALS AND METHODS: The in vitro safety of M. griffoniana ethanolic extract was assayed by MTT in human mammary epithelial (HMEC) and mouse neuronal (HT-22) cells and its lethal dose 50 (LD50) was estimated following OECD 423 guidelines. For estrogenicity, in vitro the well known E-screen assay on MCF-7 cells was performed and in vivo four groups of OVX rats were treated either with 75, 150 and 300 mg/kg M. griffoniana extract doses or estradiol (1 mg/kg BW) for three days; and changes in uterine and vagina were analyzed. Then, for neuroprotective effect, Alzheimer-type dementia induction was achieved by scopolamine (1.5 mg/kg B.W., i.p.) injection four days/week and M. griffoniana extract as well as piracetam (standard) were administered daily for 2 weeks to evaluate the extract's neuroprotective potential. The endpoints were the assessment of learning and working memory, oxidative stress state (SOD, CAT, and MDA) in brain, acetylcholine esterase (AChE) activity and the histopathological changes in hippocampus. RESULTS: No toxic effect was observed when incubating mammary (HMEC) and neuronal (HT-22) cells with M. griffoniana ethanol extract for 24 h and its LD50 was found >2000 mg/kg. The extract also exhibited both in vitro and in vivo estrogenic activities, displayed by a significant (p < 0.01) increment in MCF-7 cells population in vitro and an increase in the epithelium height of the vagina and the wet weight of the uterus mainly with the 150 mg/kg BW extract dose compared to untreated OVX rats. The extract also reversed scopolamine-induced memory impairment in rat by improving learning, working and reference memory. This was associated with an increment in CAT and SOD expression, alongside a decrement in MDA content and AChE activity in hippocampus. Further, the extract reduced neuronal cell loss in hippocampal structures (CA1, CA3 and dentate gyrus). High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) spectra, revealed the presence of numerous phytoestrogens in M. griffoniana extract. CONCLUSION: M. griffoniana ethanolic extract has estrogenic, anticholinesterase and antioxidant activities that could account for its anti-amnesic effects. These findings therefore sheds light on why this plant is commonly used in the therapy of menopausal complaints and dementia.

Hydromethanolic Root Extract of Gnidia Kraussiana Demonstrates Anti-Inflammatory Effect Through Anti-Oxidant Activity Enhancement in a Rodent Model of Gout.

Gout is a metabolic arthritis that originates from increased accumulation of monosodium urate (MSU) crystals in joints. This work aimed to evaluate the antioxidant and anti-inflammatory activities of the hydromethanolic extract of Gnidia kraussiana (HEGK) using model of Gouty arthritis on mice. The total polyphenol, flavonoid, tannin content and the antioxidant activity of HEGK were also evaluated. MSU-injected mice were treated daily for 3 days with HEGK (25, 50 and 100 mg/kg). Indomethacin and colchicin were used as reference drugs. Paw oedema and body temperature were measured at different time intervals post-injection. Malondialdehyde, acid phosphatase, ß-Galactosidase, catalase, superoxide dismutase and glutathione levels were evaluated. HEGK is rich in polyphenol (129.93 mg/100 g), flavonoid (67.78 mg/100 g) and tannin conferring it a high antioxidant activity. Acute oral toxicity of HEGK resulted in LD50 greater than 2000 mg/kg. Oral administration of HEGK induced a significant decrease in the oedema of legs injected with urate crystals and reduced the release of acid phosphatase and ß-Galactosidase. A model of oxidative damage was successfully established, revealing a significant increase in malondialdehyde and inhibition of antioxidants, including superoxide dismutase, catalase and glutathione activity. Thus, HEGK can actively inhibit the effect of inflammatory mediators in gouty arthritis.

In Vitro and In Vivo Antiproliferative Actions of Solanum gilo Raddi (Solanaceae) Fruit Extract on Breast Tissues.

Background: Menopause is a normal event characterized by a drop in estrogen's production, leading to numerous symptoms. To face these later, women rely on hormone replacement therapy (HRT), which alleviates numerous menopausal symptoms. Unfortunately, long-term exposure to estrogens is associated with an increase in endometrial and breast cancers. This study dealt with the evaluation of in vitro and in vivo antiproliferative effects of Solanum gilo Raddi, a plant used in folk medicine to treat tumors in Cameroon. Materials and Methods: The in vitro antiproliferative effect of S. gilo fruit extract was investigated through the well-characterized MTT assay in one normal and three cancerous breast cells. For the in vivo study, one normal group (NOR) of rats received distilled water (vehicle), and five other groups (n = 6) were treated either with tamoxifen (3.3 mg/kg BW) as standard or with the vehicle (negative control) or S. gilo fruit hydroethanolic extract (125, 250, and 500 mg/kg BW). The treatments were administered concomitantly with the E2V to induce breast hyperplasia for 16 weeks, and the endpoints were the histopathology of the mammary glands and some biochemical parameters. Results: The S. gilo extract significantly inhibited human (MCF-7 and MDA-MB-231) and rodent (4T1) breast carcinoma cell growth. Rats exposed only to E2V presented atypical mammary hyperplasia compared to the normal parenchyma observed in normal rats. While rats treated with S. gilo extract at the dose of 125 mg/kg BW showed a microarchitecture of mammary glands with moderate hyperplasia, the higher doses (250 and 500 mg/kg) inhibited mammary gland hyperplasia compared to the E2V group. Conclusion: S. gilo fruit extract has antiproliferative constituents that could help to fight against estrogen-dependent breast cancer, thanks to their ability to scavenge free radicals, as exhibited in this study.

Epidemiological, clinical and therapeutic characteristics of metastatic spinal cord compression in prostate cancer patients in two tertiary hospitals in Cameroon.

Introduction: prostate cancer represents the 3rd primary neoplasia responsible for metastatic spinal cord compression (MSCC). MSCC is an extreme oncological emergency, because it involves both functional and vital prognosis. The present study aimed to establish a pattern of MSCC in prostate cancer patients in Douala and Yaoundé general hospitals (Cameroon). Methods: this was a descriptive and retrospective study in the Radiotherapy and Medical Oncology services at both Douala and Yaoundé General Hospitals. The explored variables were general characteristics of the study population, clinical and paraclinical features, management and outcomes. Furthermore 5-year survival was analyzed by the Kaplan-Meier method. Logistic regression by determining the odd ratios and their 95% confidence was done using "Statistical Package for Social Sciences" (SPSS 23) software. The difference was considered significant at p < 0.05. Results: our series consisted of 151 patients out of which the mean age was 66.88 (SD: 8.71) years (95% CI: 44-88). Pain was the most common clinical symptom (53.33%; n= 80) and fracture-settlement accounted for majority (60%; n= 90.61) of the pain. Thoracic spine damage was encountered by 47.02% (n= 71). Patients received a total doses of irradiation between 20 and 30 gray (Gy). The main toxicity due to radiotherapy were asthenia (45.70%; n= 69.11). The overall survival at 5 years was 90.11%. Factors associated with fracture-settlement were smoking (aOR 10.04, 95% CI: 2.09-48.12; p = 0.004) and the localization of MSCC occurred (aOR 0.21, 95% CI: 0.05-0.77; p = 0.02). Conclusion: in summary the average age for developing the condition is 66.88 years and factors associated with fracture-settlement were smoking and the localization of MSCC. Back pain was the most common clinical sign and fracture-settlement was the first type of injury on medical magnetic resonance imaging. Therefore, we recommend that emphasis should be placed on increasing awareness of the population on the importance of early diagnosis.

Effects of Hibiscus sabdariffa Calyxes Aqueous Extract on Antioxidant Status and Histopathology in Mammary Tumor-Induced in Rats.

Breast cancer is a major threat worldwide. Hibiscus sabdariffa is widely consumed as beverage in sub-Saharan Africa for its anticancer potential. The present study therefore aimed at scientifically verifying its anticancer effect in rats. For this, 48 Wistar rats (∼55 days) were treated either with tamoxifen at 3.3 mg/kg BW (standard) or with a decoction of H. sabdariffa (125, 250, and 500 mg/kg BW) or distilled water (vehicle). Breast cancer was induced by a single dose of 50 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA). At the end of the 21 weeks of treatment, the tumor incidence, tumor morphology, histopathology, as well as some biochemical parameters in the tumors were assessed. As a result, 86% of DMBA's rats developed mammary tumors. The H. sabdariffa extract (125 and 250 mg/kg) reduced tumor incidence by 63% and 75%, respectively; inhibited tumor burden by 84.86% and 38.78%, respectively, and decreased tumor volume by more than 72% compared to the DMBA group. It also protected rats against DMBA-induced diffuse breast neoplasia, and the optimal effect was recorded at 125 mg/kg. Furthermore, it significantly increases the SOD activity and decreases the MDA level. In summary, H. sabdariffa has antibreast tumor and antioxidant properties in rats, which could justify its common use to treat cancer.

Epidemiological and clinical profile, and survival of patients followed for breast cancer between 2010 and 2015 at the Yaounde General Hospital, Cameroon.

INTRODUCTION: approximately 6000 Cameroonian women died of cancer in 2018, and the breast is the most affected with 2625 new cases. The aim of this study was to establish a pattern of malignant breast tumours in Yaoundé (Cameroon). METHODS: this study was a descriptive and analytical retrospective study of breast cancer between January 2010 and December 2015 in Yaoundé General Hospital (YGH) after the Institutional ethics committee approval. The variables studied were the socio-demographic characteristics, risk factors for breast cancer, types of tumours and type of treatments. The 5-year survival was analyzed by the Kaplan-Meier method. The adjusted hazard ratios and their 95% confidence intervals were calculated to assess the association between studied variables and patient survival through the cox regression using SPSS 23 software. The difference was considered significant at p < 0.05. RESULTS: among the 344 files collected in this study, breast cancer patients were predominantly female (96.64%, n = 288) aged 45.39 ± 13.35 years, with invasive ductal carcinoma (68.03%, n = 270), located in the left breast (52%, n= 147). The average tumour size was ~6.5 ± 0.3 cm and diagnosed in grade II of Scarf Bloom Richardson (SBR) in 60% (n= 150) of cases. The 5-year survival was 43.3%. Factors associated with this poor survival were the religion (aHR 5.05, 95% CI: 1.57 - 16.25; p = 0.007 for animist and aHR 4.2, 95% CI: 1.53 - 11.46; p = 0.005 for protestant), location of the tumour (aHR 6.24, 95% CI: 1.58 - 24.60; p = 0.012), tumor height (aHR 0.21, 95% CI: 0.04 - 1.11; p = 0.011) and the time spent before medical treatment (aHR 5.12, 95% CI: 0.39 - 8.38; p = 0.011). CONCLUSION: the young age, large tumour size and high histological grade in our studied population suggest a weak awareness of women about breast cancer. Action should be taken in early screening to improve the management of breast cancer in Cameroon.

Anti-breast cancer potential of Anonidium mannii (Oliv.) Engl. & Diels barks ethanolic extract: UPLC-ESI-QTOF-MS detection of anticancer alkaloids.

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer is a serious threat in low-income as well as developed countries. To face this, many herbal preparations are prescribed by traditional healers in Cameroon, among which is Anonidium mannii commonly called "wild soursop". AIM: This study was undertaken to assess the anti-tumor effect of A. mannii ethanolic extract on cancer cell growth and against DMBA-induced mammary tumors in rats. MATERIALS AND METHODS: The well characterized MTT bioassay was used to assess the cytotoxic potential of A. mannii ethanolic extract in liver (HepG2), prostate (DU145 & PC3) and breast (MCF-7) cancer cell lines. Considering the fact that breast cells were the most sensitive to the extract, a 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast tumor rat model was used to assess the possible anticancer effect of A. mannii extract. Indeed, rats were treated with either tamoxifen (3.3 mg/kg BW) or A. mannii extract (16.5, 50 and 150 mg/kg BW) or vehicle (2% ethanol) for 20 weeks. Tumor incidence, tumor mass and volume, oxidative stress status in tumor as well as tumor histoarchitecture were evaluated. RESULTS: A 24 h incubation of tested cells with the A. mannii extract significantly slowed cell growth in a concentration-dependent manner with an interesting effect in breast cells (IC50 ~61.5 µg/mL). As compared to the DMBA rats, those treated with A. mannii extract (50 and 150 mg/kg) showed reduced breast tumor incidence (28%), tumor burden (95.34% at 50 mg/kg and 99.14% at 150 mg/kg) and tumor volume (~92%). A. mannii extract counteracted the high proliferation of terminal mammary ducts induced by DMBA, mainly at 50 mg/kg. Furthermore, the extract decreased MDA and nitrite levels but increased SOD activity in the mammary gland. High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) analysis detected potential anticancer and antioxidant alkaloids in A. manni extract, which are close to those found in Annona muricata. CONCLUSION: These results provide evidence on the in vitro and in vivo anticancer effects of A. mannii, and therefore support its use in traditional medicine system to fight against cancer.

Regular consumption of "Nkui", a Cameroonian traditional dish, may protect against cardiovascular and bone disorders in an estrogen deficiency condition.

OBJECTIVES: There is a growing body of evidence indicating the potential of culinary herbs and spices to decrease the incidence of several chronic diseases or conditions. Because of this, the WHO recommends their regular consumption. In the Cameroonian culinary practices, "Nkui" is a famous dish made from a mixture of 10 spices. In our previous study, the ethanolic extract of this mixture exhibited promising estrogenic properties. Thus, this study aimed to evaluate its protective effects on some menopause-related cardiovascular and bone disorders. METHODS: For this purpose, a post-menopause-like model (ovariectomized rats) has been used. Animals were orally treated with the "Nkui" extract for 60 days. The investigation focused on the oxidative stress status, endothelial function (NO bioavailability), lipid profile, and bone mass, biochemical (calcium and inorganic phosphorus contents, serum alkaline phosphatase activity) and histomorphological features. RESULTS: The extract regulated lipid metabolism in a way to prevent accumulation of abdominal fat, gain in body weight and increased atherogenic indexes induced by ovariectomy. It prevented menopause-related low levels of nitric oxide and oxidative stress damage by increasing superoxide dismutase and catalase activities, while reducing glutathione and malondialdehyde levels in the heart and aorta. Moreover, it prevented ovariectomy-induced bone mass loss, bone marrow disparities and the disorganization of the trabecular network. It also increased femur calcium and inorganic phosphorus contents. CONCLUSIONS: These results suggest that a regular consumption of "Nkui" may have health benefits on cardiovascular system and osteoporosis, major health issues associated with menopause.

The antimammary tumor effects of ethanolic extract of propolis from Adamawa region (Cameroon) are by apoptosis via reactive oxygen species-mediated mitochondrial pathway.

Identification of novel natural treatment to combat cancer is a current need. This study was aimed at assessing the anticancer effects of ethanol-extracted Cameroonian propolis (EEP). The antitumor effect of EPP was evaluated in vitro by measuring; cell viability, cell cycle, cell death mechanism, cell migration/invasion, reactive oxygen species (ROS), mitochondrial potential (ΔΨm), caspase activity, and apoptosis-regulating proteins (Bcl-2 and Bcl-XL) in cell lines. In vivo, the effect of EEP against 7,12 dimethylbenz(a)anthracene (DMBA)-induced breast tumorigenesis in rats was assessed. EEP was found to induce cytotoxicity against ER negative MDA-MB-231 breast cancer cells by activating apoptosis through ROS-mediated mitochondrial pathway. The extract equally triggered caspase-3 and caspase-9, increment of ROS level, disruption of ΔΨm and down-regulation of Bcl-XL and Bcl-2 proteins. Besides, EPP prevented migration and invasion activities by inhibiting MMP-2 activity. At all doses it prevented breast tumor incidence (20% in EEP 150 mg/kg vs 70% in DMBA) as well as tumor burden. Tumor sections from EEP-treated rats showed middle proliferation of mammary ducts with weak inflammatory responses. In summary, Cameroonian propolis exhibited antimammary tumor effects via the intrinsic pathway of apoptosis.

Oral administration of tartrazine (E102) accelerates the incidence and the development of 7,12-dimethylbenz(a) anthracene (DMBA)-induced breast cancer in rats.

BACKGROUND: Despite the considerable advances made in the treatment of cancer, it remains a global threat. Tartrazine (E102) is a synthetic dye widely used in food industries; it has recently been shown to induce oxidative stress (a well known risk factor of cancer) in rat tissues. The present work therefore aimed to assess the impact of a regular consumption of tartrazine on the incidence of breast cancer in rats. METHODS: Forty (40) Wistar rats aged 55 to 60 days were randomly assigned into 5 groups (n = 8) including two groups serving as normal controls and receiving distilled water (NOR) or tartrazine (NOR + TARZ). The three remaining groups were exposed to the carcinogen DMBA (50 mg/kg) and treated for 20 weeks with either distilled water (DMBA), tartrazine 50 mg/kg (DMBA + TARZ) or a natural dye (DMBA + COL). The parameters evaluated were the incidence, morphology and some biomarkers (CA 15-3, estradiol and α-fetoprotein) of breast cancer. The oxidative status and histomorphology of the tumors were also assessed. RESULTS: A regular intake of tartrazine led to an early incidence of tumors (100% in rats that received TARZ only vs 80% in rats that received DMBA only), with significantly larger tumors (p < 0.001) (mass = 3500 mg/kg and volume = 4 cm3). The invasive breast carcinoma observed on the histological sections of the animals of the DMBA + TARZ group was more developed than those of the DMBA group. The increase in serum α-fetoprotein (p < 0.05) and CA 15-3 (p < 0.01) levels corroborate the changes observed in tumors. The presence of oxidative activity in animals of the DMBA + TARZ group was confirmed by a significant decrease (p < 0.001) in the activity of antioxidant enzymes (SOD and catalase) as well as the level of GSH and increase in the level of MDA compared to the rats of the DMBA and NOR groups. CONCLUSION: Tartrazine therefore appears to be a promoter of DMBA-induced breast tumorigenesis in rats through its oxidative potential. This work encourages further studies on the mechanisms of action of tartrazine (E102) and its limits of use.

Abyssinone V-4' Methyl Ether, a Flavanone Isolated from Erythrina droogmansiana, Exhibits Cytotoxic Effects on Human Breast Cancer Cells by Induction of Apoptosis and Suppression of Invasion.

Abyssinone V-4' methyl ether (AVME) isolated from Erythrina droogmansiana was recently reported to exhibit anti-mammary tumor effect in mice. The present work was therefore aimed at elucidating its cellular and molecular mechanisms. To achieve our goal, the cytotoxicity of AVME against tumoral and non-tumoral cell lines was evaluated by resazurin reduction test; flow cytometry allowed us to evaluate the cell cycle and mechanisms of cell death; the mitochondrial transmembrane potential, reactive oxygen species (ROS) levels, and caspase activities as well as apoptosis-regulatory proteins (Bcl-2 and Bcl-XL) were measured in MDA-MB-231 cells. Further, the antimetastatic potential of AVME was evaluated by invasion assay. AVME exhibited cytotoxic effects in all tested tumor cell lines and induced a significant increase in the percentage of MDA-MB-231 cells at G2/M and S phases of the cell cycle in a concentration-dependent manner. AVME also induced apoptosis in MDA-MB-231 cells, which was accompanied by the activation of caspase-3 and caspase-9 and downregulation of Bcl-2 and Bcl-XL proteins. Moreover, AVME suppressed cancer cell invasion by the inhibition of the metalloproteinase-9 activity. Findings from this study suggest that AVME has anti-breast cancer activities expressed through mitochondrial proapoptotic pathway including impairment of aggressive behaviors of breast cancer cells.

Ethanol-extracted Cameroonian propolis: Antiproliferative effects and potential mechanism of action in prostate cancer.

The present study was conducted to evaluate in vitro and in vivo antiproliferative potential of the Cameroonian propolis and to elucidate its underlying mechanism. In vitro, ethanol-extracted propolis (EEP) was tested on cell growth, cell proliferation, cell cycle, cell death mechanism and cell migration. The cell cycle- and apoptosis-regulating proteins were assessed by Western blotting. In vivo the testosterone-induced benign prostatic hyperplasia (BPH) in Wistar rat was used to evaluate the antiproliferative potential of EEP. EEP reduced DU145 and PC3 cell survival with an IC50 of 70 and 22 µg/ml respectively. It increased the number of late apoptotic cells, the amount of cells in G0/G1 phase in DU145 and PC3 cells at 50 µg/ml. Cell cycle proteins (cdk1, pcdk1 and their related cyclins A and B) were down-regulated in both DU145 and PC3 cells, while cdk2 and pcdk2 were down-regulated only in PC3 cells. The pro-apoptotic Bax protein was up-regulated, while the anti-apoptotic Akt and pAKT, and Bcl-2 proteins were down-regulated. It increased prostate cell adhesion and chemotaxis. EEP reduced prostate weight, volume and epithelial thickness in rats. We demonstrated for the first time that Cameroonian propolis is endowed with in vitro and in vivo antiproliferative properties in the prostate.

Daucosterol from Crateva adansonii DC (Capparaceae) reduces 7,12-dimethylbenz(a)anthracene-induced mammary tumors in Wistar rats.

This study aimed to evaluate the in vivo anticancer effects of daucosterol which was earlier reported to possess in vitro anticancer effects. Breast tumor was induced in 30 rats using the environmental carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) while 6 control rats received olive oil (NOR). Animals with palpable tumors were randomized into five groups (n = 6) each as follows: negative control group treated with the vehicle (DMBA); positive control group treated with 5 mg/kg BW doxorubicin (DOXO + DMBA); three groups treated with daucosterol at doses of 2.5, 5, and 10 mg/kg BW (DAU + DMBA). Treatment lasted 28 days afterward, tumor (mass, volume, cancer antigen [CA] 15-3 level and histoarchitecture), hematological and toxicological parameters were examined. The tumor volume gradually increased in the DMBA group during the 28 days, with a tumor volume gain of ∼390 cm3 . Daucosterol at all doses reduced tumor volume (∼133.7 cm3 at 10 mg/kg) as well as protein, malondialdehyde (MDA), and CA 15-3 levels compared to DMBA rats. Tumor sections in daucosterol-treated rats showed a lower proliferation of mammary ducts with mild (5 and 10 mg/kg) to moderate (2.5 mg/kg) inflammatory responses. Moreover, it exhibited an antioxidant effect, evidenced by a significant and dose-dependent decreased in MDA levels, as well as an increase in catalase activity compared to the DMBA group. Daucosterol showed for the first time in vivo antitumor effects that corroborate its previous in vitro effects.