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Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells
Yu-Hua Zeng1, Lin-Yun Zhou1, Qian-Zhao Chen1
1Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
Abstract:
Colon cancer is common worldwide and accounts for the significant cancer related morbidity and mortality in patients. Although extensive advancement has been made in colon cancer treatment and diagnosis in the last decades, there is still a giant gap between the clinical expectation. It has been reported that resveratrol (Res) may be a potential candidate for cancer treatment. However, the specific mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Res in human colon cancer cells, and unveiled the possible mechanism for this effect. With cell viability, flow cytometry, PCR and western blot analysis, we demonstrated the efficacious anticancer activity of Res in HCT116 cells. Mechanically, we found that Res greatly upregulates BMP7 in HCT116 cells. Exogenous BMP7 enhances the anticancer effect of Res in HCT116 cells, which was almost reversed by the BMP7 specific antibody. Res does not activate the BMPs/Smads signaling, but decreases the phosphorylation of Akt1/2/3 substantially in HCT116 cells. Exogenous BMP7 enhances the inhibitory effect of Res on the phosphorylation of Akt1/2/3, while BMP7 immunodepletion reverses this effect notably. Res markedly decreases the phosphorylation of PTEN, which can be enhanced by exogenous BMP7 but partly reversed by the BMP7 antibody. Our findings suggested that Res may be a promising candidate for colon cancer treatment, and the anticancer activity may be mediated by inactivating PI3K/Akt signaling through upregulating BMP7 to decrease, at least, the phosphorylation of PTEN.
Insights
Resveratrol shows anticancer effects in colon cancer cells by upregulating BMP7. This mechanism involves inactivating the PI3K/Akt pathway, suggesting Resveratrol as a potential colon cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Colon cancer presents a significant global health burden with ongoing challenges in treatment and diagnosis.
- Resveratrol (Res) has emerged as a potential therapeutic agent for cancer, but its precise mechanisms remain largely unelucidated.
- Understanding the molecular pathways influenced by Resveratrol is crucial for developing effective colon cancer therapies.
Purpose of the Study:
- To investigate the anticancer activity of Resveratrol in human colon cancer cells (HCT116).
- To elucidate the underlying molecular mechanism of Resveratrol's anti-colon cancer effects.
- To explore the role of Bone Morphogenetic Protein 7 (BMP7) in mediating Resveratrol's activity.
Main Methods:
- Cell viability assays to assess anticancer effects.
- Flow cytometry for cell cycle analysis.
- Polymerase Chain Reaction (PCR) and Western blot analysis to evaluate gene and protein expression and phosphorylation.
- Experiments involving exogenous BMP7 and BMP7-specific antibodies to confirm pathway involvement.
Main Results:
- Resveratrol demonstrated significant anticancer activity in HCT116 colon cancer cells.
- Resveratrol treatment led to a notable upregulation of BMP7 expression in HCT116 cells.
- The anticancer effects of Resveratrol were enhanced by exogenous BMP7 and diminished by BMP7 inhibition.
- Resveratrol inhibited the phosphorylation of Akt1/2/3 and PTEN, key components of the PI3K/Akt signaling pathway.
- BMP7 upregulation by Resveratrol was found to be critical for the observed inactivation of the PI3K/Akt pathway.
Conclusions:
- Resveratrol exhibits promising anticancer properties against colon cancer cells.
- The mechanism involves the upregulation of BMP7, which subsequently inactivates the PI3K/Akt signaling pathway.
- Resveratrol represents a potential therapeutic candidate for colon cancer, warranting further clinical investigation.
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