Bhargava Arpit, Pathak Neelam, Seshadri Sriram, Bunkar Neha, Mishra Dinesh K, Lohiya Nirmal K, Mishra Pradyumna K
Translational Research Laboratory, School of Biological Sciences, Dr. Harisingh Gour Central University, Sagar, India.
Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India.
Anticancer Agents Med Chem. 2018;18(13):1860-1874. doi: 10.2174/1871520618666171229223919.
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.
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.
We assessed the nano-encapsulated flavonoid-rich fraction isolated from a traditional Indian herb (Sanjeevani) (NP.SB). Both and studies were performed to evidence the epigenetic protection mechanisms of NP.SB through a mitochondrial-targeted pre-clinical validation strategy.
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. 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 findings.
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.
