Dandawate Prasad R, Subramaniam Dharmalingam, Jensen Roy A, Anant Shrikant
Department of Surgery, The University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
Department of Surgery, The University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, KS 66160, USA; The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
Semin Cancer Biol. 2016 Oct;40-41:192-208. doi: 10.1016/j.semcancer.2016.09.001. Epub 2016 Sep 5.
Breast cancer is the most common form of cancer diagnosed in women worldwide and the second leading cause of cancer-related deaths in the USA. Despite the development of newer diagnostic methods, selective as well as targeted chemotherapies and their combinations, surgery, hormonal therapy, radiotherapy, breast cancer recurrence, metastasis and drug resistance are still the major problems for breast cancer. Emerging evidence suggest the existence of cancer stem cells (CSCs), a population of cells with the capacity to self-renew, differentiate and be capable of initiating and sustaining tumor growth. In addition, CSCs are believed to be responsible for cancer recurrence, anticancer drug resistance, and metastasis. Hence, compounds targeting breast CSCs may be better therapeutic agents for treating breast cancer and control recurrence and metastasis. Naturally occurring compounds, mainly phytochemicals have gained immense attention in recent times because of their wide safety profile, ability to target heterogeneous populations of cancer cells as well as CSCs, and their key signaling pathways. Therefore, in the present review article, we summarize our current understanding of breast CSCs and their signaling pathways, and the phytochemicals that affect these cells including curcumin, resveratrol, tea polyphenols (epigallocatechin-3-gallate, epigallocatechin), sulforaphane, genistein, indole-3-carbinol, 3, 3'-di-indolylmethane, vitamin E, retinoic acid, quercetin, parthenolide, triptolide, 6-shogaol, pterostilbene, isoliquiritigenin, celastrol, and koenimbin. These phytochemicals may serve as novel therapeutic agents for breast cancer treatment and future leads for drug development.
乳腺癌是全球女性中诊断出的最常见癌症形式，也是美国癌症相关死亡的第二大主要原因。尽管有了更新的诊断方法、选择性以及靶向化疗及其联合疗法、手术、激素疗法、放射疗法，但乳腺癌复发、转移和耐药性仍然是乳腺癌的主要问题。新出现的证据表明存在癌症干细胞（CSCs），这是一群具有自我更新、分化能力且能够启动和维持肿瘤生长的细胞。此外，癌症干细胞被认为与癌症复发、抗癌药物耐药性和转移有关。因此，靶向乳腺癌症干细胞的化合物可能是治疗乳腺癌以及控制复发和转移的更好治疗剂。天然存在的化合物，主要是植物化学物质，近年来因其广泛的安全性、靶向异质性癌细胞群体以及癌症干细胞及其关键信号通路的能力而备受关注。因此，在本综述文章中，我们总结了目前对乳腺癌症干细胞及其信号通路的理解，以及影响这些细胞的植物化学物质，包括姜黄素、白藜芦醇、茶多酚（表没食子儿茶素-3-没食子酸酯、表没食子儿茶素）、萝卜硫素、染料木黄酮、吲哚-3-甲醇、3,3'-二吲哚甲烷、维生素E、视黄酸、槲皮素、小白菊内酯、雷公藤内酯醇、6-姜烯酚、紫檀芪、异甘草素、雷公藤红素和柯因宁。这些植物化学物质可能作为乳腺癌治疗的新型治疗剂以及药物开发的未来先导。
