Arpit Bhargava, Neelam Pathak, Sriram Seshadri, Neha Bunkar, Dinesh K. Mishra, Nirmal K. Lohiya and Pradyumna K. Mishra* Pages 1860 - 1874 ( 15 )
Background: Novel bioactive plant secondary metabolites, including flavonoids, offer a spectrum of chemo-protective responses against a range of human tumor models. However, the clinical translation of these promising anti-cancer agents has been hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration.
Objective: To circumvent the challenges associated with herbal drug development and for effective integration into clinical setting, nano-engineering is one of the emerging pragmatic strategies which has promise to deliver therapeutic concentrations of bio-actives upon oral administration.
Method: We assessed the nano-encapsulated flavonoid-rich fraction isolated from a traditional Indian herb Selaginella bryopteris (Sanjeevani) (NP.SB). Both in vitro and in vivo studies were performed to evidence the epigenetic protection mechanisms of NP.SB through a mitochondrial-targeted pre-clinical validation strategy.
Results: The mito-protective activity of NP.SB revealed a dose-dependent effect when tested in GC-1 spg (mouse spermatogonial epithelial) and B/CMBA.Ov (mouse ovarian epithelial) following exposure to Nsuccinimidyl N-methylcarbamate, a potential human carcinogen. Smaller size, rapid internalization, faster mobility and site specific delivery conferred significant cancer protection in cultured cells. Notably, this encapsulated flavonoid supplementation; prevented emergence of neoplastic daughter clones from senescent mother phenotypes in pro-oxidant treated GC-1 spg and B/CMBA.Ov cells by selective abrogation of mitochondrial oxidative stress-induced aberrant epigenetic modifications. In vivo studies using a diethylnitrosamine and 2- acetylaminofluorene mouse model demonstrated that NP.SB has a significant inhibitory effect on tumor growth which clearly substantiated our in vitro findings.
Conclusion: Anti-carcinogenic property in conjunction with low toxicity of NP.SB, underscores the translational significance of dietary flavonoids as cancer-protective agents for preferential application in clinical settings.
Cancer prevention, anti-cancer agents, epigenetic modifier, isocyanate, translational oncology, dietary flavonoids.
Translational Research Laboratory, School of Biological Sciences, Dr. Harisingh Gour Central University, Sagar, Centre for Advanced Studies in Zoology, University of Rajasthan, Jaipur, Department of Biochemistry, Nirma Univesity, Ahmedabad, Translational Research Laboratory, School of Biological Sciences, Dr. Harisingh Gour Central University, Sagar, School of Pharmacy and Technology Management, Narsee Monjee Institute of Management Studies, Shirpur, Centre for Advanced Studies in Zoology, University of Rajasthan, Jaipur, Translational Research Laboratory, School of Biological Sciences, Dr. Harisingh Gour Central University, Sagar