Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells

Abstract

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

Targeting chemoresistant colorectal cancer via systemic administration of a BMP7 variant

“…Here, we have shown that even though PTEN increased moderately upon BMP7v treatment, PI3K protein expression, and AKT activation levels decreased significantly in CD44v6 + cells, which differentiate and revert to CD44v6 − /PI3K low cells. This mechanism is in line with the observation that the natural compound resveratrol inhibits the PI3K pathway by upregulating the BMP7 in human colon cancer cells [44]. The induction of differentiation may represent an alternative therapeutic approach to render CSCs sensitive to standard therapies [24,45].…”

AKT as a Therapeutic Target for Cancer

“…Resveratrol (RES) is found in grapes, berries, and peanuts and inhibited activation of multiple survival pathways, including the PI3K/AKT pathway, thereby inducing cancer cell apoptosis (86,87). RES reportedly inhibited proliferation and migration of hepatocellular carcinoma and colon cancer cells through the downregulation of the PI3K/AKT pathway by modifying sirtuin 1-mediated posttranslational modification and elevating bone morphogenetic protein 7 (88,89). RES induced apoptosis by specifically targeting pAKT and mediators of apoptosis in H460 lung cancer cells (90).…”

Resveratrol protects Leydig cells from nicotine‐induced oxidative damage through enhanced autophagy

“…Resveratrol (trans-3,5,4′-trihydroxystilbene), a natural phytoalexin found in red wine, peanuts, berries and many other botanicals, displays a range of pharmacological properties including anti-inflammatory, 18 anti-oxidative, 19 anti-thrombotic 20 and antiproliferative properties. 21 Although numerous studies have proven that resveratrol reflected strong anti-oxidative capacities, particularly excellent scavenging activities, 19,22 whereas its availability in protecting male reproductive function as an antioxidant is still elusive. Therefore, to explore the potential application of resveratrol in protecting male reproductive function and to elucidate the potential underlying mechanism, nicotine-induced Leydig cells were used as a model of oxidative damage.…”