Kim Rae-Kwon, Uddin Nizam, Hyun Jin-Won, Kim Changil, Suh Yongjoon, Lee Su-Jae
Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
College of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju-si 690-756, Republic of Korea.
Toxicol Appl Pharmacol. 2015 Aug 1;286(3):143-50. doi: 10.1016/j.taap.2015.03.026. Epub 2015 Apr 2.
Poor prognosis of breast cancer patients is closely associated with metastasis and relapse. There is substantial evidence supporting that cancer stem-like cells (CSCs) are primarily responsible for relapse in breast cancer after anticancer treatment. However, there is a lack of suitable drugs that target breast cancer stem-like cells (BCSCs). Here, we report that phloroglucinol (PG), a natural phlorotannin component of brown algae, suppresses sphere formation, anchorage-independent colony formation and in vivo tumorigenicity. In line with these observations, treatment with PG also decreased CD44(+) cancer cell population as well as expression of CSC regulators such as Sox2, CD44, Oct4, Notch2 and β-catenin. Also, treatment with PG sensitized breast cancer cells to anticancer drugs such as cisplatin, etoposide, and taxol as well as to ionizing radiation. Importantly, PG inhibited KRAS and its downstream PI3K/AKT and RAF-1/ERK signaling pathways that regulate the maintenance of CSCs. Taken together, our findings implicate PG as a good candidate to target BCSCs and to prevent the disease relapse.
乳腺癌患者预后不良与转移和复发密切相关。有大量证据支持癌症干细胞样细胞（CSCs）是抗癌治疗后乳腺癌复发的主要原因。然而，缺乏针对乳腺癌干细胞样细胞（BCSCs）的合适药物。在此，我们报告间苯三酚（PG），一种褐藻中的天然间苯三酚单宁成分，可抑制球体形成、非锚定依赖性集落形成和体内致瘤性。与这些观察结果一致，PG处理还减少了CD44(+)癌细胞群体以及CSC调节因子如Sox2、CD44、Oct4、Notch2和β-连环蛋白的表达。此外，PG处理使乳腺癌细胞对顺铂、依托泊苷和紫杉醇等抗癌药物以及电离辐射敏感。重要的是，PG抑制了调节CSCs维持的KRAS及其下游PI3K/AKT和RAF-1/ERK信号通路。综上所述，我们的研究结果表明PG是靶向BCSCs和预防疾病复发的良好候选药物。
