Kasdagly Maria, Radhakrishnan Sridhar, Reddivari Lavanya, Veeramachaneni D N Rao, Vanamala Jairam
Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado, USA.
Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado, USA; Department of Food Science, Penn State University, University Park, Pennsylvania, USA.
Nutrition. 2014 Nov-Dec;30(11-12):1242-56. doi: 10.1016/j.nut.2014.02.016. Epub 2014 Mar 12.
Colon cancer strikes more than 1 million people annually and is responsible for more than 500,000 cancer deaths worldwide. Recent evidence suggests that the majority of malignancies, including colon cancer are driven by cancer stem cells (CSCs) that are resistant to current chemotherapeutic approaches leading to cancer relapse. Wnt signaling plays a critical role in colon stem cell renewal and carcinogenesis. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a Wnt target gene, and aldehyde dehydrogenase 1 B1 (ALDH1B1) are good markers for normal and malignant human colon stem cells. Diet contributes to 20% to 42% of all human cancers and 50% to 90% of colon cancer. Recent evidence shows that the Western diet has a causative link to colon cancer; however, mechanisms of action are not fully elucidated. Western diet-induced obesity elevates systemic insulin-like growth factor-1 and insulin levels, which could lead to elevated proliferation and suppressed apoptosis of CSCs through PI3K/AKT/Wnt pathway. Although conventional chemotherapy targets the PI3K/AKT pathways and can significantly reduce tumor size, it fails to eliminate CSCs and has serious side effects. Dietary bioactive compounds such as grape seed extract, curcumin, lycopene, and resveratrol have promising chemopreventive effects, without serious side effects on various types of cancers due to their direct and indirect actions on CSC self-renewal pathways such as the Wnt pathway. Understanding the role of CSCs in diet-induced colon cancer will aid in development of evidence-based dietary chemopreventive strategies and/or therapeutic agents targeting CSCs.
结肠癌每年影响超过100万人，在全球导致超过50万例癌症死亡。最近的证据表明，包括结肠癌在内的大多数恶性肿瘤是由癌症干细胞（CSCs）驱动的，这些细胞对目前的化疗方法具有抗性，导致癌症复发。Wnt信号通路在结肠干细胞更新和致癌过程中起关键作用。富含亮氨酸重复序列的G蛋白偶联受体5（LGR5）是一种Wnt靶基因，醛脱氢酶1 B1（ALDH1B1）是正常和恶性人类结肠干细胞的良好标志物。饮食导致所有人类癌症的20%至42%以及结肠癌的50%至90%。最近的证据表明，西方饮食与结肠癌有因果关系；然而，其作用机制尚未完全阐明。西方饮食引起的肥胖会升高全身胰岛素样生长因子-1和胰岛素水平，这可能通过PI3K/AKT/Wnt途径导致CSCs增殖增加和凋亡受抑制。虽然传统化疗靶向PI3K/AKT途径并能显著缩小肿瘤大小，但它无法消除CSCs且有严重副作用。膳食生物活性化合物如葡萄籽提取物、姜黄素、番茄红素和白藜芦醇具有有前景的化学预防作用，由于它们对CSC自我更新途径如Wnt途径的直接和间接作用，对各种类型的癌症没有严重副作用。了解CSCs在饮食诱导的结肠癌中的作用将有助于制定基于证据的膳食化学预防策略和/或靶向CSCs的治疗药物。
