Friedman Jamie R, Perry Haley E, Brown Kathleen C, Gao Ying, Lin Ju, Stevenson Cathyrn D, Hurley John D, Nolan Nicholas A, Akers Austin T, Chen Yi Charlie, Denning Krista L, Brown Linda G, Dasgupta Piyali
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
Department of Biology, Alderson Broaddus University, Philippi, WV 26416, United States.
Biochem Pharmacol. 2017 Apr 1;129:54-66. doi: 10.1016/j.bcp.2017.01.004. Epub 2017 Jan 16.
Small cell lung cancer (SCLC) is characterized by excellent initial response to chemotherapy and radiation therapy with a majority of the patients showing tumor shrinkage and even remission. However, the challenge with SCLC therapy is that patients inevitably relapse and subsequently do not respond to the first line treatment. Recent clinical studies have investigated the possibility of camptothecin-based combination therapy as first line treatment for SCLC patients. Conventionally, camptothecin is used for recurrent SCLC and has poor survival outcomes. Therefore, drugs which can improve the therapeutic index of camptothecin should be valuable for SCLC therapy. Extensive evidence shows that nutritional compounds like capsaicin (the spicy compound of chili peppers) can improve the anti-cancer activity of chemotherapeutic drugs in both cell lines and animal models. Statistical analysis shows that capsaicin synergizes with camptothecin to enhance apoptosis of human SCLC cells. The synergistic activity of camptothecin and capsaicin is observed in both classical and variant SCLC cell lines and, in vivo, in human SCLC tumors xenotransplanted on chicken chorioallantoic membrane (CAM) models. The synergistic activity of capsaicin and camptothecin are mediated by elevation of intracellular calcium and the calpain pathway. Our data foster hope for novel nutrition based combination therapies in SCLC.
小细胞肺癌（SCLC）的特点是对化疗和放疗的初始反应良好，大多数患者会出现肿瘤缩小甚至缓解。然而，SCLC治疗面临的挑战是患者不可避免地会复发，随后对一线治疗无反应。最近的临床研究探讨了以喜树碱为基础的联合疗法作为SCLC患者一线治疗的可能性。传统上，喜树碱用于复发性SCLC，生存结果较差。因此，能够提高喜树碱治疗指数的药物对SCLC治疗应该具有重要价值。大量证据表明，辣椒素（辣椒中的辛辣成分）等营养化合物可以在细胞系和动物模型中提高化疗药物的抗癌活性。统计分析表明，辣椒素与喜树碱协同作用可增强人SCLC细胞的凋亡。在经典和变异SCLC细胞系中以及在体内接种于鸡胚绒毛尿囊膜（CAM）模型的人SCLC肿瘤中均观察到喜树碱和辣椒素的协同活性。辣椒素和喜树碱的协同活性是由细胞内钙和钙蛋白酶途径的升高介导的。我们的数据为SCLC基于营养的新型联合疗法带来了希望。
