Cryptotanshinone Prevents the Binding of S6K1 to mTOR/Raptor Leading to the Suppression of mTORC1-S6K1 Signaling Activity and Neoplastic Cell Transformation
- Authors
- Jeoung, Nam Ho; Jeong, Ji Yun; Kang, Bong Seok
- Issue Date
- 30-Jun-2021
- Publisher
- 대한암예방학회
- Keywords
- mTORC1; p70S6K; neoplastic cell transformation; cryptotanshinone; Raptor protein
- Citation
- 대한암예방학회지, v.26, no.2, pp 145 - 152
- Pages
- 8
- Journal Title
- 대한암예방학회지
- Volume
- 26
- Number
- 2
- Start Page
- 145
- End Page
- 152
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/18757
- DOI
- 10.15430/JCP.2021.26.2.145
- ISSN
- 2288-3649
2288-3657
- Abstract
- Cryptotanshinone is known for its inhibitory activity against tumorigenesis in various human cancer cells. However, exact mechanisms underlying the anticancer effects of cryptotanshinone are not fully elucidated. Here, we propose a plausible molecular mechanism, wherein cryptotanshinone represses rapamycin-sensitive mTORC1/S6K1 mediated cancer cell growth and cell transformation. We investigated the various effects of cryptotanshinone on the mTORC1/S6K1 axis, which is associated with the regulation of cell growth in response to nutritional and growth factor signals. We found that cryptotanshinone specifically inhibited the mTORC1-mediated phosphorylation of S6K1, which consequently suppressed the clonogenicity of SK-Hep1 cells and the neoplastic transformation of JB6 Cl41 cells induced by insulin-like growth factor-1. Finally, we observed that cryptotanshinone prevented S6K1 from binding to the Raptor/mTOR complex, rather than regulating mTOR and its upstream pathway. Overall, our findings provide a novel mechanism underlying anti-cancer effects cryptotanshinone targeting mTORC1 signaling, contributing to the development of anticancer agents involving metabolic cancer treatment.
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Collections - College of Medicine > Department of Internal Medicine > 1. Journal Articles
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