Maharjan Sony, Park Byoung Kwon, Lee Su In, Lim Yoonho, Lee Keunwook, Kwon Hyung-Joo
Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 05029, Republic of Korea.
Biomol Ther (Seoul). 2018 May 1;26(3):322-327. doi: 10.4062/biomolther.2017.235.
A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.
一种在雌激素受体、孕激素受体和人表皮生长因子受体等三种分子标记物上存在缺陷的乳腺癌被称为三阴性乳腺癌（TNBC）。由于预后较差，许多TNBC患者的生存率低于其他类型的患者。在本研究中，我们证实了天然化合物戈米辛G在TNBC癌细胞中的抗癌作用。用戈米辛G处理可抑制两种TNBC细胞系MDA-MB-231和MDA-MB-468的活力，但对非TNBC细胞系如MCF-7、T47D和ZR75-1没有影响。为了研究这种活性的分子机制，我们检测了用戈米辛G处理MDA-MB-231细胞后的信号转导通路。戈米辛G未诱导细胞凋亡，但显著抑制AKT磷酸化，并减少视网膜母细胞瘤肿瘤抑制蛋白（Rb）和磷酸化Rb的量。戈米辛G以蛋白酶体依赖性方式诱导细胞周期蛋白D1减少。因此，戈米辛G导致细胞周期停滞在G1期。相比之下，T47D细胞除AKT磷酸化略有降低外，没有显著变化。这些结果表明，戈米辛G通过抑制TNBC细胞增殖而非诱导凋亡发挥抗癌活性。我们的研究表明，戈米辛G可作为治疗TNBC患者的治疗药物。
