Anticancer role of mango (Mangifera indica L.) peel and seed kernel extracts against 7,12- dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rats.

Breast cancer is the second leading cause of cancer death among women. The present study is an effort to reveal the antiproliferative and antioxidant actions of mango seed kernel extract (KE), peel extract (PE), and their combination (KEPE) on mammary tumors induced by 7,12 dimethylbenz[a]anthracene (DMBA). Seven groups of adult female Sprague-Dawley rats were prepared, including C: (control), DMBA: (rats were administered with DMBA), (DMBA-KE), (DMBA-PE), and (DMBA-KEPE): rats were administered with DMBA and then treated with KE, PE, and (both KE and PE), respectively, (KE) and (PE): rats were administered with KE and PE, separately. The study focused on the assessment of markers of endocrine derangement [serum 17-ß estradiol (E2)], apoptosis [caspase-3 and deoxyribonucleic acid fragmentation (DNAF)], and oxidative stress [lipid peroxidation and antioxidants (glutathione, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase)]. Histopathological examination and immunohistochemical expression of caspase-3 and estrogen receptor-α (ER-α) in mammary gland tissues (MGTs) were determined, as well as the characterization of mango extracts. The results showed that DMBA administration induced mammary tumors by increasing cell proliferation and evading apoptosis. In addition, DMBA administration caused oxidative stress by the production of reactive oxygen species, which increased lipid peroxidation and decreased cellular antioxidants, allowing cancer to progress. In contrast, treatment with DMBA-KE, DMBA-PE, or DMBA-KEPE diminished mammary tumors induced by DMBA, where they reduced oxidative stress via increased antioxidant parameters including reduced glutathione, superoxide dismutase, total glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Also, different treatments decreased proliferation through the reduction of E2, and ER-α expression levels. However, these treatments increased the apoptosis of unwanted cells as they increased caspase-3 activity and DNAF. All these changes led to the prevention of breast injuries and the reduction of mammary tumors. This demonstrates that the contents of mango extracts, especially phenolics and flavonoids, have an important role in mammary tumor treatment through their potential antioxidant, antiproliferative, proapoptotic, and anti-estrogenic effects. KE and PE administration for 4 weeks had no adverse effects. Conclusion: Each of KE, PE, and KEPE has a therapeutic effect against DMBA-induced mammary tumors via induction of apoptosis and reduction of each of the OS, proliferation, and estrogenic effects. So, they can play an important role in the pharmacological tole.

The Implication of microRNAs as non-invasive biomarkers in 179 Egyptian breast cancer female patients.

Background: MicroRNAs (miRs) are small (19-25 nucleotides), non-protein coding RNAs that regulate gene expression, and thus play essential roles in cell cycle progression. The evidence has demonstrated that the expression of several miRs is dysregulated in human cancer. Methods: The study includes 179 female patients and 58 healthy women Patients were identified as luminal A, B, Her-2/neu, and basal-like, as well as classified into I, II, and III stages. Analysis of the expression fold change of miR-21 and miR-34a with molecular markers, including the oncogene Bcl-2 (B-cell lymphoma 2) and the tumor suppressor genes BRCA1 (breast cancer susceptibility gene 1), BRCA2 (breast cancer susceptibility gene 2), and the tumor suppressor protein p53, was carried out for all patients, pre- and post-chemotherapy, and for all healthy women. Results: At diagnosis (pre-chemotherapy), miR-21 was up-regulated (p < 0.001), while miR-34a was down-regulated (p < 0.001). Post-chemotherapy, the expression of miR-21 decreased significantly (p < 0.001), while the expression of miR-34a increased significantly (p < 0.001). Conclusion: miR-21 and miR-34a may be helpful to non-invasive biomarkers to evaluate the response of breast cancer to chemotherapy.

In Vitro Collapsing Colon Cancer Cells by Selectivity of Disulfiram-Loaded Charge Switchable Nanoparticles Against Cancer Stem Cells.

BACKGROUND: Different strategies against colon cancer are accompanied by treatment failure, because of drug toxicity toward normal cells and cancer stem cells (CSCs) resistance. However, previous patent evaluated liposome that encapsulated inhibitor of CSCs' aldehyde dehydrogenase (ALDH)1; disulfiram, for targeting breast CSCs. Liposome has disadvantages due to its hydrophobicity. OBJECTIVES: Designing hydrophilic nanoparticles has selectivity to release disulfiram in CC cells rather than in normal colonocytes based on variation in microenvironment between normal and cancer cells. METHODS: Disulfiram was nanoformulated by its loading into cationic chitosan and coating with anionic albumin. Their selectivity and targeting were investigated using murine and human colon cancer cells compared to normal mice colon cells. RESULTS: Zeta potential of the coated nanoparticles confirmed that albumin-layering confers negative charge (-10.3mv) for disulfiram-loaded chitosan nanoparticles (52.9mv). In slightly acidic medium of tumor, the ionic bond between albumin and chitosan hydrolyzed then the positive charge was reversed (47.6mv). Thus coated nanoparticles showed higher sustain release for disulfiram in tumor microenvironment than neutral pH and their uptake was higher in cancer cells than normal cells. This interpreted the highest selectivity of coated nanoparticles for enhancing apoptosis and eliminating CSCs in cancer cells. CONCLUSION: These patented coated nanoparticles were the most effective and selective for eradicating colon CSCs without insulting normal stem cells in comparison with disulfiram which was toxic to both normal and CSCs. This novel study that used charge switchable (hydrophilic) nanoparticles for targeting colon CSCs may represent a basis for future in vivo studies.

Protective role of hesperidin against γ-radiation-induced oxidative stress and apoptosis in rat testis.

BACKGROUND: Gamma (γ) ray, an electromagnetic radiation, is occasionally accompanying the emission of an alpha or beta particle. Exposure to such radiation can cause cellular changes such as mutations, chromosome aberration and cellular damage which depend upon the total amount of energy, duration of exposure and the dose. Ionizing radiation can impair spermatogenesis and can cause mutations in germ cells. In general, type B spermatogonia are sensitive to this type of radiation. The current study was carried out to evaluate the protective role of hesperidin (H), as a polyphenolic compound, on rat testis injury induced by γ-radiation. METHODS: Rats were divided into groups including C group (control rats), R (irradiated) group (rats irradiated with γ-radiation), Vehicle (V) group (rats administered with dimethylsulfoxide "DMSO"), H group (rats administered with H only), HR and RH groups (rats treated with H before and after exposure to γ-radiation, respectively). Malondialdehyde (MDA: the end product of lipid peroxidation "LPO") and xanthine oxidase (XO: it generates reactive oxygen species "ROS") in testes homogenate as well as nitric oxide (NO: as ROS) in mitochondrial matrix were determined. The apoptotic markers including DNA-fragmentation (DNAF) in testes homogenate and calcium ions (Ca2+) in mitochondrial matrix were determined. Superoxide dismutase (SOD) and catalase (CAT) activities in testes homogenate, while reduced glutathione "GSH" in nuclear matrix were determined. Also histopathological examination for testes tissues through electron microscope was studied. RESULTS: Exposure of rats to γ-radiation (R group) increased the levels of MDA, NO, DNAF, Ca2+ and XO activity, while it decreased GSH level, SOD and CAT activities as compared to the C groups; γ-radiation increased oxidative stress (OS), LPO, apoptosis and induced testes injuries. These results are in agreement with the histopathological examination. In contrast, treatment with H before or after exposure to γ-radiation (HR and RH groups, respectively) decreased the levels of MDA, NO, DNAF and Ca2+ but increased GSH level and the activities of SOD, CAT and XO as compared to R group and this indicates that H decreased OS, LPO and apoptosis. Also, the histopathological results showed that H improved testis architecture and this is related to the antioxidant and anti-apoptotic activities of H contents. Protection is more effective when H is given before rather than after exposure. Finally, administration of H to healthy rats for a short period had no adverse affect on testes cells. CONCLUSION: Hesperidin showed antioxidant and anti-apoptotic activities. It has a protective role against OS, injury and apoptosis induced by γ-radiation in testes. Protection is more effective when H is given before rather than after exposure.Graphical Abstract.

Imbalanced Diet Deficient in Calcium and Vitamin D- Induced Juvenile Osteopenia in Rats; the Potential Therapeutic Effect of Egyptian Moghat Roots Water Extract (Glossostemon bruguieri).

This study aimed to explore and validate a new juvenile osteopenic (JO) rat model then examine the efficacy of moghat (Glossostemon bruguieri) as an alternative reversal therapy for JO. Phytochemical screening analysis showed that moghat contains 5.8% alkaloids, 1.5% flavonoids and 13.2% total phenols. Juvenile osteopenia was induced in 15 days old Sprague- Dawley female rats by feeding them free Ca and vitamin D synthetic diet for 21 days. Osteopenic rats were either treated with moghat (0.8 g dried plant tissue/Kg body weight, orally), or with a reference nutritional supplements of calcium chloride (14 mg Ca/Kg) and vitamin D3 (7 IU/Kg), for extra 21 days. Both untreated and treated groups were compared to a control group that fed a regular pelleted food. Our results showed that osteopenic rats lost normal bone tissue architecture, 30 % of body mass, 54 % of bone mass and finally 93% of bone calcium mass. Furthermore, these rats showed a markedly increase in serum phosphate, PTH, alkaline phosphatase, aspartate transaminase activities and creatinine level as compared to the control group. Moghat administration was successfully reversed osteopenia by normalizing body and bone masses to the reference ranges, increased the bone calcium mass by 17 fold without any detectable side effects on liver and kidney physiological performance. Therefore, moghat could be considered as potent safe -JO- reversal extract.

Protective role of Punica granatum (pomegranate) peel and seed oil extracts on diethylnitrosamine and phenobarbital-induced hepatic injury in male rats.

The present study is an attempt to reveal the protective role of Punica granatum peel and seed oil extracts against diethylnitrosamine (DEN) and phenobarbital (PB) induced hepatic injury in rats. DEN administration increased the levels of malondialdehyde (MDA), DNA fragmentation, caspase-3 and glutathione reductase (GSR) activities, while the level of reduced glutathione (GSH) and the activities of superoxide dismutase (SOD), glutathione S-transferase (GST) and total glutathione peroxidase (t-GPx) were decreased compared with the control. Treatment with peel and seed oil extracts pre, during and post DEN administration improved liver functions, decreased the levels of MDA, DNA fragmentation, caspase-3 and GSR activities with an elevation in levels of GSH, SOD, GST and t-GPx activities. This indicates that these extracts reduced the oxidative stress and apoptosis induced by DEN. Also the effect of administration of PE and SOE separately for a long time (23 weeks) on healthy rats was studied.