02406nas a2200289   4500008004100000022001400041245015700055210006900212260000800281300000900289490000600298520137000304100002201674700002701696700001901723700001901742700003101761700003601792700001801828700002001846700002301866700002101889700003401910700001601944700003301960856012301993       2018                        eng d  a2045-232200aStreptomyces sp metabolite(s) promotes Bax mediated intrinsic apoptosis and autophagy involving inhibition of mTOR pathway in cervical cancer cell lines0 aStreptomyces sp metabolites promotes Bax mediated intrinsic apop  cFEB  a28100 v83 a<p>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.</p>1 aDan, Vipin, Mohan1 aMuralikrishnan, Balaji1 aSanawar, Rahul1 aVinodh, J., S.1 aBurkul, Bhushan, Bapusaheb1 aSrinivas, Kalanghad, Puthankala1 aLekshmi, Asha1 aPradeep, N., S.1 aDastager, Syed, G.1 aSanthakumari, B.1 aSanthoshkumar, Thankayyan, R.1 aKumar, Ajay1 aPillai, Madhavan, Radhakrish  uhttps://library.ncl.res.in/content/streptomyces-sp-metabolites-promotes-bax-mediated-intrinsic-apoptosis-and-autophagy