ArticleScientific reports2018
Streptomyces sp metabolite(s) promotes Bax mediated intrinsic apoptosis and autophagy involving inhibition of mTOR pathway in cervical cancer cell lines.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025Review
- Article
- Artificial intelligence in microbial natural product drug discovery: current and emerging role.Natural product reports · 2022Review
- The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products.Antioxidants (Basel, Switzerland) · 2022Review
- Beyond controlling cell size: functional analyses of S6K in tumorigenesis.Cell death & disease · 2022Review
- Therapeutic applications and biological activities of bacterial bioactive extracts.Archives of microbiology · 2021Review
- Therapeutic Potential of Natural Products in Treatment of Cervical Cancer: A Review.Nutrients · 2021Review
- An Overview of Novel Agents for Cervical Cancer Treatment by Inducing Apoptosis: Emerging Drugs Ongoing Clinical Trials and Preclinical Studies.Frontiers in medicine · 2021Review
- Arsenite-induced apoptosis can be attenuatedToxicology research · 2019Article
- mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer.Frontiers in oncology · 2019Review
- Advances and Challenges in Cervical Cancer: From Molecular Mechanisms and Global Epidemiology to Innovative Therapies and Prevention Strategies.Cancer control : journal of the Moffitt Cancer CenterReview
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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