Vipin, Mohan Dan and Balaji , Muralikrishnan and Rahul , Sanawar and Vinodh , J. S and Kalanghad Puthankalam, Srinivas and Asha, Lekshmi and T R. , Santhoshkumar and R. , Ajay Kumar (2018) Streptomyces sp metabolite(s) promotes Bax mediated intrinsic apoptosis and autophagy involving inhibition of mTOR pathway in cervical cancer cell lines. scientific reports. ISSN 2045-2322

Text Streptomyces sp metabolite (Sci Reports).pdf Restricted to Registered users only Download (1998Kb) | Request a copy

Abstract

In cervical cancer, the association between HPV infection and dysregulation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway (PI3K/AKT/mTOR pathway) places mTOR as an attractive therapeutic target. The failure of current treatment modalities in advanced stages of this cancer and drawbacks of already available mTOR inhibitors demand for novel drug candidates. In the present study we identified the presence of a mTOR inhibitor in an active fraction of the ethyl acetate extract of Streptomyces sp OA293. The metabolites(s) in the active fraction completely inhibited mTORC1 and thereby suppressed activation of both of its downstream targets, 4E-BP1 and P70S6k, in cervical cancer cells. In addition, it also stalled Akt activation via inhibition of mTORC2. The mechanism of mTOR inhibition detailed in our study overcomes significant drawbacks of well known mTOR inhibitors such as rapamycin and rapalogs. The active fraction induced autophagy and Bax mediated apoptosis suggesting that mTOR inhibition resulted in programmed cell death of cancer cells. The molecular weight determination of the components in active fraction confirmed the absence of any previously known natural mTOR inhibitor. This is the first report of complete mTOR complex inhibition by a product derived from microbial source.

Item Type:	Article
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	20 Jun 2018 06:59
Last Modified:	20 Jun 2018 06:59
URI:	http://rgcb.sciencecentral.in/id/eprint/612

Actions (login required)

View Item