Inhibitory role of a smart nano-trifattyglyceride of Moringa oleifera root in epithelial ovarian cancer, through attenuation of FSHR - c-Myc axis

辣木根智能纳米三脂肪酸甘油酯通过减弱 FSHR - c-Myc 轴对上皮性卵巢癌具有抑制作用

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作者:Arijit Ghosh, Tanaya Roychowdhury, Rajesh Nandi, Rituparna Maiti, Narendra N Ghosh, Sabir A Molla, Soma Mukhopadhyay, Chandraday Prodhan, Keya Chaudhury, Priyabrata Das, Nirmal K Sarkar, Samit Chattopadhyay, Rittwika Bhattacharya, Chinmoy K Bose, Dilip K Maiti

Aim

Epithelial ovarian cancer has the deadliest prognosis amongst gynaecological cancers, warranting an unmet need for newer drug targets. Based on its anticancer as well as abortifacient potential, Moringa oleifera Lam. root was hypothesized to have some implications in follicle stimulating hormone receptor (FSHR) dependent cancers like epithelial ovarian cancer. Experimental procedure: Effect of Moringa oleifera Lam. root extract (MRE) was studied in epithelial ovarian cancer cell line through in vitro studies viz. MTT assay, clonogenic assay, cell cycle analysis, flow cytometry, western blot analysis, immunocytochemical analysis of FSHRand c-Myc expression and in vivo studies viz. effect of MRE in mice model of ovarian carcinoma. The structure of the active compound of MRE was elucidated following solvent extraction, purification through column chromatography, preparative TLC and bioactivity guided structural identification through 1H-NMR, 13C-NMR, DEPT-135, ESIMS,FT-IR spectrophotometry, UV-vis-NIR spectrophotometry and DFT study.

Conclusion

Crude MRE displayed cytotoxic activity, induced apoptosis, and attenuated expression of FSHR and c-Myc in ovarian cancer cell line OAW42. MRE also attenuated expression of CD31, FSHR, and c-Myc in tumour xenograft mouse model. Finally, the active compound purified from ethyl acetate-n-hexane subfraction ofMRE, that attenuated viability of ovarian carcinoma cell lines and reduced FSHR and c-Myc expression, was identified as a naturally hydrated-trifattyglyceride, showing aDFT-optimized folded amphipathic structure for easy transportation through hydrophilic and hydrophobic regions in a biological system, indicating its immense therapeutic relevance in epithelial ovarian carcinoma.

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