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As previous studies showed, resveratrol-induced autophagy suppresses cancer in vitro and in vivo. Therefore, we examined whether resveratrol-induced suppression of cancer progression occurred through mTOR and inhibition of ULK1. To examine mTOR dependency on resveratrol induced-cancer cell suppression, we utilized two different cell lines that were previously reported mTOR inhibition sensitive and insensitive, respectively. MCF7, a breast cancer cell that has constitutive PI3K activation and higher mTOR activity so that it is sensitive to mTOR inhibitor, showed very sensitive response to resveratrol treatment. However, neither PP242 nor resveratrol reduced the viability of Ras transformed colorectal cancer cells,
SW620. This result indicates that resveratrol effect on cancer cell viability is largely dependent on impact of mTOR, which varies in cancer cell types. To examine whether the effect of resveratrol on cellular viability is reflected in intra-cellular signaling, we measured mTOR activity in MCF7 and SW620 cells upon resveratrol and PP242 treatment. The basal level of mTOR activity and responsiveness to resveratrol and PP242 were significantly lower in SW620 cells compared to MCF7 cells, further demonstrating that the modulation of mTOR activity is involved in the physiological effects of resveratrol.
Next, we examined whether ULK1 is involved in resveratrol-induced suppression of cancer cell viability. Like knockdown of ULK1 blunted the autophagy induction by resveratrol, reduction of viability of MCF7 cells was partially restored by ULK1 knockdown. This restoration of viability was also observed in PP242 induced cancer cell suppression. These cancer cell specific and ULK1 dependent effect of resveratrol further supports the idea that resveratrol-induced cellular behavior alterations occurred through mTOR-ULK1 pathway.
Article Produced By
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Republic of Korea
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763238/
(All these Articles can be read with this URL:
https://markethive.com/group/ama/blog/the-role-of-resveratrol-in-achieving-optimal-health-p5 )
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