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.

Ethanol-Extracted Cameroonian Propolis Counteracts Tamoxifen-Induced Endometrial Hyperplasia by Modulating Apoptosis and Proliferation-Regulating Proteins in the Ovaries of Intact Wistar Rats.

Tamoxifen is the most common adjuvant that has been widely used in the treatment of positive estrogen receptor (ER+) breast cancer for over 20 years. However, long term exposure to tamoxifen doubles the risk of endometrial cancer. The association of tamoxifen with antiproliferative substances could abrogate its side effects on the endometrium. Recently, we demonstrated that ethanol-extracted Cameroonian propolis (EECP) has chemopreventive effects on ER+ breast cancer in rats. This study evaluated the capability of EECP to counteract tamoxifen-induced endometrial hyperplasia, without altering its effect on the breast. Thirty-six rats of ∼2 months were coadministered either EECP (16.5, 50, and 150 mg/kg BW) or fulvestrant (300 µg/kg BW) and tamoxifen (10 mg/kg BW) for 8 weeks. Afterward, the relative weights and histomorphometry of the uterus, vagina, ovaries, and mammary gland were assessed. The expression of some proteins of proliferation (PCNA), angiogenesis (VEGF), and apoptosis (Bax, Bcl-2, and caspase-3) was measured by immunohistochemistry. Rats that received only tamoxifen had endometrial hyperplasia compared to normal rats. EECP and fulvestrant protected the rats against tamoxifen-induced endometrial hyperplasia. A significant decrease in uterine wet weight (p < 0.01); endometrial height (p < 0.001); and expression of PCNA, Bcl-2, and VEGF proteins as well as a significant increase in the expression of Bax and caspase-3 proteins was observed in the EECP group compared to the Tamox group. EECP did not change the effects of tamoxifen on the breast. In summary, Cameroonian propolis which is efficacious in preventing breast cancer can also be a good complementary medicine to prevent tamoxifen-induced endometrial cancer in tamoxifen users.

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.

Potential of Regular Consumption of Cameroonian Neem (Azadirachta indica L.) Oil for Prevention of the 7,12-Dimethylbenz(a)anthracene-Induced Breast Cancer in High-Fat/Sucrose-Fed Wistar Rats.

Neem (Azadirachta indica) is a tree from the Meliaceae family native to India, where it is considered as one of the most important plants worldwide. The anticancer effects of neem oil on breast cancer cells have been recently reported; however, its in vivo effects have not been studied. This prompted us to investigate the protective effects of neem oil on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in high-fat/sucrose-fed Wistar rats. Juvenile female Wistar rats were treated either with neem oil at a dose of 3 mL/kg body weight at 3 different frequencies, 2 times/week (Neem 1), 4 times/week (Neem 2), and every day (Neem 3), or with tamoxifen (3.3 mg/kg body weight), starting 1 week prior to DMBA treatment and lasting 12 weeks. Incidence, burden, volume, and histological analysis of mammary tumors were measured. Further toxicological parameters have been assessed. No tumors were detected in rats from the normal group, while all the rats from the negative control group (100%) developed mammary tumors. The regular consumption of neem oil at a dose of 3 mL/kg (2 or 4 times/week) significantly (p < 0.01) and in a dose-dependent manner reduced tumor incidence (80%), burden [35.78% (2 times/week) and 36.09% (4 times/week)], and weight. Neem consumption protected rats against DMBA-induced breast hyperplasia, with an optimal effect when taken 4 times weekly. Interestingly, all the animals that received a daily dose of 3 mL/kg died at the third week of the experiment. Further, animals that took the neem oil 4 times per week developed hepatotoxicity, evidenced by an increase of liver wet weight, transaminase (ALT and AST) activity, and histological abnormalities in liver. This study brings insight into the use of neem oil, which is greatly appreciated in traditional medicine. In summary, we demonstrated for the first time that the regular consumption of neem oil prevents breast cancer, but its excessive consumption is toxic.

Abyssinone V-4' Methyl Ether Isolated from Erythrina droogmansiana (Leguminosae) Inhibits Cell Growth and Mammary Glands Hyperplasia Induced in Swiss Mice by the 7,12-Dimethylbenz(a)anthracene.

There is a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. The present study was designed to evaluate the in vitro and in vivo antiproliferative effects of Abyssinone V-4' methyl ether (AVME) on breast tissue of mice. The cytotoxicity of AVME was evaluated using MTT assay in four cancer cell lines (DU145, PC3, HepG2, and MCF-7). Further, a protective effect of AVME was evaluated on 7,12-dimethylbenz(a)anthracene- (DMBA-) induced breast tumor in Swiss mice. Incidence, burden, volume, and histological analysis of mammary tumors were measured. As a result, AVME inhibits DU145, PC3, HepG2, and MCF-7 cells growth. In vivo, no tumor was detected in mice from the normal group as compared to those of DMBA group. Moreover, AVME inhibits the DMBA-induced mammary glands hyperplasia in mice at the dose of 10 mg/kg, evidenced by a decrease of tumor incidence, tumor weight, and volume as well as a protective effect against the lobular alveolar hyperplasia. Taken all together, these results suggest that Abyssinone V-4' methyl ether is endowed with antitumor properties and could be a source of traditional medicine which deserves to be more elucidated and explored in the foreseeable future.

The hydro-ethanolic extract of Acacia seyal (Mimosaceae) stem barks induced death in an ER-negative breast cancer cell line by the intrinsic pathway of apoptosis and inhibited cell migration.

BACKGROUND: Despite the significant developments occurring in the treatment of cancer, it still remains the second deadly disease, responsible for 8.2 million deaths every year. Various natural substances have been studied for active molecules of tumor suppression in the past and the tropical flora, by its diversity, continues to provide new antitumor drugs. Acacia seyal is a plant used in Cameroonian traditional system to treat cancer. It exhibited cytotoxic effects towards human breast adenocarcinoma cells. The present work was therefore designed to elucidate the underlying mechanisms by which A. seyal extract induced its cytotoxic effect. METHODS: The cell death mechanism (apoptosis or necrosis) and cell cycle analyses were assessed using flow cytometry. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), caspases activities as well as Bcl-2 and Bcl-xL protein contents were assessed in MDA-MB-231 cells. Afterwards, cell migration/invasion was also assessed. RESULTS: The A. seyal extract induced apoptosis in MDA-MB-231 cells, while it failed to do so in MCF-7 cells. It induced cell cycle arrest in G2/M phase. Further it induced a decrease in ΔΨm, an increase in ROS levels and caspases activities as well as a down regulation in Bcl-2 and Bcl-xL protein contents in MDA-MB-231 cells. Moreover, A. seyal extract exhibited anti-migration, anti-invasion activities in MDA-MB-231 cells. CONCLUSION: These results demonstrate that A. seyal extract induced its antitumor effects mainly by interference in metastasis related events, by triggering apoptosis through a ROS-mediated mitochondrial pathway.

In Vitro Cytotoxicity and In Vivo Antimammary Tumor Effects of the Hydroethanolic Extract of Acacia seyal (Mimosaceae) Stem Bark.

The present study was designed to evaluate the in vitro and in vivo antitumor effects of A. seyal hydroethanolic extract on breast cancer. The cytotoxicity of A. seyal extract was evaluated using resazurin reduction assay in 9 cell lines. Further, the protective effect of the hydroethanolic extract of A. seyal stem barks was evaluated on 7,12-dimethylbenz(a)anthracene- (DMBA-) induced breast cancer rat model. Incidence, burden, volume, and histological analysis of mammary tumors were measured. The Acacia seyal extract exhibited CC50 of 100 in MCF-7 cells after 24 h. In vivo, no tumors were detected in rats from the control group, while 11 rats out of 12 (91.66%) developed mammary tumors in the DMBA-exposed group receiving only the vehicle. Acacia seyal extract significantly (p < 0.01) and in the dose-dependent manner reduced tumor incidence (3 rats out of 12 at the dose of 300 mg/kg), burden [62.1% (150 mg/kg) and 65.8% (300 mg/kg)], and mass. It protected rats against DMBA-induced breast hyperplasia, with an optimal effect at the dose of 300 mg/kg. Taken altogether, these results suggest that the hydroethanolic extract of Acacia seyal might contain phytoconstituents endowed with antitumoral properties, which could protect against the breast cancer induced in rats.

Crateva adansonii DC, an African ethnomedicinal plant, exerts cytotoxicity in vitro and prevents experimental mammary tumorigenesis in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Crateva adansonii DC is a plant traditionally used in Cameroon to treat constipation, asthma, snakebites, postmenopausal complaints and cancers. AIM: The anticancer potential of the dichloromethane/methanol extract of C. adansonii stem barks was investigated using human breast cancer cell and 7,12 dimethylbenz(a)anththracene (DMBA)-induced mammary tumorigenesis model in rats. MATERIAL AND METHODS: The cytotoxicity of C. adansonii extract was assessed in vitro towards breast carcinoma (MCF-7 and MDA-MB-231) and non-tumoral cell lines (NIH/3T3 and HUVEC) by Alamar Blue assay. Furthermore, in vivo studies were performed on female Wistar rats treated either with C. adansonii extract at a dose of 75 or 300mg/kg body weight or with tamoxifen (3.3mg/kg body weight), starting 1 week prior DMBA treatment and lasted 12 weeks. The investigation focused on tumour burden, tumour DNA fingerprint, morphological, histological, hematological, and biochemical parameters. RESULTS: CC50 values for the in vitro assays were 289µg/mL against MCF-7 cells and >500µg/mL in others cells, leading to a selectivity index ≥1.73. C. adansonii extract significantly (p<0.001) revealed in vivo the reduction of the cumulative tumour yield (87.23%), total tumour burden (88.64%), average tumour weight (71.11%) and tumour volume (78.07%) at the dose of 75mg/kg as compared to DMBA control group. A weak effect was also observed at 300mg/kg. This extract showed a moderate hyperplasia at the dose of 75mg/kg while at 300mg/kg no significant change was noted as compared to DMBA group. It protected rats from the DNA alteration induced by DMBA and increased antioxydant enzymes activities in mammary gland tissue homogenates. In addition, Ultra-High Performance Liquid Chromatography/ESI-QTOF-Mass Spectrometry analysis of C. adansonii extract detected structure-related of many well-known anticancer agents such as flavane gallate, flavonol, phenylpropanoïds, sesquiterpene derivatives, gallotannins and lignans. The LD50 of C. adansonii was estimated to be greater than 5000mg/kg. CONCLUSIONS: These aforementioned results suggest that the C. adansonii extract may possess antitumor constituents, which could combat breast cancer and prevent chemically-induced breast cancer in rats.