Department of Life Science and Biochemical Engineering, Graduate School, Sun Moon University, Asan 31460, Republic of Korea.
Department of Pharmaceutical Engineering and Biotechnology, Sun Moon University, Asan 31460, Republic of Korea.
Molecules. 2023 Sep 23;28(19):6783. doi: 10.3390/molecules28196783.
Triple-negative breast cancer (TNBC) is a highly aggressive type of breast cancer and has a poor prognosis. As standardized TNBC treatment regimens cause drug resistance and tumor recurrence, the development of new TNBC treatment strategies is urgently required. Bufotalin is a bufadienolide isolated from the skin and parotid venom glands of the toad , and has several pharmacological properties, including antiviral, anti-inflammatory, and anticancer activities. However, the anticancer effect and underlying molecular mechanisms of action of bufotalin in TNBC have not been fully studied. In the current study, we investigated the effects of bufotalin on the growth and metastasis of MDA-MB-231 and HCC1937 TNBC cells. Bufotalin potently inhibited the proliferation of both TNBC cell lines by promoting cell cycle arrest and caspase-mediated apoptosis. Furthermore, bufotalin effectively suppressed the migration and invasion of both TNBC cell lines by regulating the expression of key epithelial-mesenchymal transition (EMT) biomarkers, matrix metalloproteinases (MMPs), and integrin α6. Notably, the anticancer effect of bufotalin in TNBC cells was associated with the downregulation of the signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Collectively, our results suggest that the natural compound bufotalin may exert antiproliferative and antimetastatic activities in TNBC cells by modulating the apoptotic pathway and the STAT3/EMT axis.
三阴性乳腺癌（TNBC）是一种侵袭性很强的乳腺癌，预后较差。由于标准化的 TNBC 治疗方案会导致药物耐药和肿瘤复发，因此迫切需要开发新的 TNBC 治疗策略。蟾毒它灵是一种从蟾蜍皮肤和腮腺毒液腺中分离出来的蟾毒配基，具有多种药理作用，包括抗病毒、抗炎和抗癌活性。然而，蟾毒它灵在 TNBC 中的抗癌作用及其潜在的分子作用机制尚未得到充分研究。在本研究中，我们研究了蟾毒它灵对 MDA-MB-231 和 HCC1937 TNBC 细胞生长和转移的影响。蟾毒它灵通过促进细胞周期停滞和半胱天冬酶介导的细胞凋亡，强烈抑制两种 TNBC 细胞系的增殖。此外，蟾毒它灵通过调节关键上皮-间充质转化（EMT）标志物、基质金属蛋白酶（MMPs）和整合素α6 的表达，有效抑制两种 TNBC 细胞系的迁移和侵袭。值得注意的是，蟾毒它灵在 TNBC 细胞中的抗癌作用与信号转导和转录激活因子 3（STAT3）信号通路的下调有关。总之，我们的研究结果表明，天然化合物蟾毒它灵可能通过调节凋亡途径和 STAT3/EMT 轴在 TNBC 细胞中发挥抗增殖和抗转移活性。
