Sharma Sharada H, Thulasingam Senthilkumar, Chellappan David Raj, Chinnaswamy Prabu, Nagarajan Sangeetha
School of Chemical and Biotechnology, SASTRA University, Thirumalaisamudram, Thanjavur 613401, Tamil Nadu, India.
Central Animal Facility, SASTRA University, Thirumalaisamudram, Thanjavur 613401, Tamil Nadu, India.
Eur J Pharmacol. 2017 Feb 5;796:20-31. doi: 10.1016/j.ejphar.2016.12.019. Epub 2016 Dec 15.
Targeting tumor metabolism by natural products is a novel approach and provides rationale for anti-cancer drug discovery. The present study aims to explore the impact of morin and/or esculetin on c-myc induced energy metabolism in 1,2-dimethylhydrazine (DMH) induced colon cancer in rats. In order to achieve this aim we analyzed the expression of glucose and glutamine transporters and the key enzymes of glycolytic pathway besides the markers of neoplastic changes viz., mucin depleted foci (MDF), beta catenin accumulated crypts (BCAC), and markers of cell proliferation viz., proliferating cell nuclear antigen (PCNA), argyrophilic nucleolar antigen (AgNOR), c-myc, c-jun and c-fos. All the parameters tested in the present study are highly influenced by the phytochemicals morin and/or esculetin in a way to prevent colon carcinogenesis. Morin and/or esculetin supplementation effectively targets tumor metabolism via β-cateinin/c-myc signaling and affects glycolysis and glutaminolysis to abrogate colon cancer in rats. The anti-cancer effect of morin is more pronounced than esculetin. The effect obtained through the combined treatment of morin and esculetin is comparable to that of individual supplementation of morin and there is no synergistic effect. Overall individual supplementation of morin scores well as a potential anticancer agent targeting glycolysis and glutaminolysis in colon cancer.
以天然产物靶向肿瘤代谢是一种新方法，为抗癌药物研发提供了理论依据。本研究旨在探讨桑色素和/或秦皮乙素对1,2 - 二甲基肼（DMH）诱导的大鼠结肠癌中c - myc诱导的能量代谢的影响。为实现这一目标，我们分析了葡萄糖和谷氨酰胺转运蛋白的表达、糖酵解途径的关键酶，以及肿瘤变化标志物，即粘蛋白缺失灶（MDF）、β - 连环蛋白积聚隐窝（BCAC），还有细胞增殖标志物，即增殖细胞核抗原（PCNA）、嗜银核仁抗原（AgNOR）、c - myc、c - jun和c - fos。本研究中测试的所有参数都受到植物化学物质桑色素和/或秦皮乙素的高度影响，其方式是预防结肠癌发生。桑色素和/或秦皮乙素补充剂通过β - 连环蛋白/c - myc信号通路有效靶向肿瘤代谢，并影响糖酵解和谷氨酰胺分解以消除大鼠结肠癌。桑色素的抗癌作用比秦皮乙素更显著。通过桑色素和秦皮乙素联合治疗获得的效果与单独补充桑色素相当，且没有协同作用。总体而言，单独补充桑色素作为一种靶向结肠癌糖酵解和谷氨酰胺分解的潜在抗癌剂表现良好。
