Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways

Abstract

BackgroundObesity is a global phenomenon and is associated with various types of cancer, including colon cancer. There is a growing interest for safe and effective bioactive compounds that suppress the risk for obesity-promoted colon cancer. Resveratrol (trans-3, 4', 5,-trihydroxystilbene), a stilbenoid found in the skin of red grapes and peanuts suppresses many types of cancers by regulating cell proliferation and apoptosis through a variety of mechanisms, however, resveratrol effects on obesity-promoted colon cancer are not clearly established.MethodsWe investigated the anti-proliferative effects of resveratrol on HT-29 and SW480 human colon cancer cells in the presence and absence of insulin like growth factor-1 (IGF-1; elevated during obesity) and elucidated the mechanisms of action using IGF-1R siRNA in HT-29 cells which represents advanced colon carcinogenesis.ResultsResveratrol (100-150 μM) exhibited anti-proliferative properties in HT-29 cells even after IGF-1 exposure by arresting G0/G1-S phase cell cycle progression through p27 stimulation and cyclin D1 suppression. Treatment with resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation. Targeted suppression of IGF-1R using IGF-1R siRNA also affected these signaling pathways in a similar manner. Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein, whereas IGF-1R siRNA treatment did not affect apoptosis. Our data suggests that resveratrol not only suppresses cell proliferation by inhibiting IGF-1R and its downstream signaling pathways similar to that of IGF-1R siRNA but also enhances apoptosis via activation of the p53 pathway.ConclusionsFor the first time, we report that resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and activation of p53, suggesting its potential role as a chemotherapeutic agent.

Induced growth of BG-1 ovarian cancer cells by 17β-estradiol or various endocrine disrupting chemicals was reversed by resveratrol via downregulation of cell cycle progression

“…Results of the present study demonstrated that RES effectively inhibited the cell proliferation increased by EDCs on BG-1 cells expressing both ERs by inducing cell cycle arrest. From previous studies, RES is known for exerting antitumorigenic effects by suppressing cell proliferation and inducing apoptosis in various cancer cells, such as colon and pancreatic cancer cells (22,23).…”

Apoptotic Effects of Resveratrol via mTOR and COX-2 Signal Pathways in MCF-7 Breast Cancer Cells

“…레스베라트롤(resveratrol)은 피토알렉신(phytoalexin)의 일종인 파이토케미컬로 포도껍질에 존재하며 레드와인과 포 도주스에 다량 함유되어 있다 [18]. 레스베라트롤은 암발생이 진행 중인 세포활동을 방해함으로써 항암작용을 하며, 심혈관 질환 예방에도 효과가 있는 것으로 알려져 있다 [12].…”

“…레스베라트롤은 암발생이 진행 중인 세포활동을 방해함으로써 항암작용을 하며, 심혈관 질환 예방에도 효과가 있는 것으로 알려져 있다 [12]. 최근에는 레스베라트롤이 전립선암에서 apoptosis를 유발하여 암세포 의 성장을 억제하며 [1], 대장암에서도 IGF-1R/Akt/Wnt 신호 경로의 억제와 p53의 활성화를 통해 apoptosis를 유도하는 것 으로 보고되었다 [18]. mTOR (Mammalian target of rapamycin)는 serin-threonine kinase의 일종으로 단백질 번역, 세포 성장, 증식 등의 물질대사 조절에서 중요한 역할을 하는 것으로 알려져 있다 [5].…”

Compounds with Antioxidant Capacity as Potential Tools Against Several Oxidative Stress Related Disorders: Fact or Artifact?

“…Resveratrol may affect all three discrete stages of carcinogenesis (initiation, promotion, and progression) by modulating signal transduction pathways that control cell division and growth, apoptosis, inflammation, angiogenesis, and metastasis (Bishayee, 2009 ). Recently, it has been shown that resveratrol suppresses IGF-1 induced cell proliferation and elevates apoptosis in human colon cancer cells, via suppression of IGF-1R/Wnt and activation of p53 signaling pathways (Vanamala et al, 2010).…”