Huang Jhen-Yu, Hsu Ta-Wen, Chen Yu-Ru, Kao Shao-Hsuan
Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan.
Division of Colorectal Surgery, Buddhist Tzu Chi Medical Foundation, Dalin Tzu Chi Hospital, Chiayi 622401, Taiwan.
Life (Basel). 2024 Aug 15;14(8):1017. doi: 10.3390/life14081017.
Rosmarinic acid (RA) has demonstrated anticancer effects on several types of malignancies. However, whether RA promotes the anticancer effect of cisplatin on colorectal cancer cells remains sketchy. This study aimed to explore whether RA potentiates the cytotoxicity of cisplatin against colon cancer cells and the underlying mechanism. Cell viability, cell cycle progression, and apoptosis was evaluated using sulforhodamine B (SRB) assay, flow cytometric analysis, and propidium iodide/Annexin V staining, respectively. Western blotting was utilized to analyze signaling pathways. Our findings showed that RA significantly enhanced the inhibitory effect on cell viability and the induction of apoptosis on the colon cancer cell lines DLD-1 and LoVo. Signaling cascade analysis revealed that the combination of RA and cisplatin jointly induced Bax and caspase activation while downregulating Bcl-2, glutathione peroxidase 4 (GPX4), and SLC7A11 in DLD-1 cells. Moreover, caspase inhibitor and ferroptosis inhibitor significantly reversed the inhibition of cell viability in response to RA combined with cisplatin. Collectively, these findings demonstrate that RA enhances the cytotoxicity of cisplatin against colon cancer cells, attributing to the promotion of apoptosis and ferroptosis.
迷迭香酸（RA）已在多种恶性肿瘤中显示出抗癌作用。然而，RA是否能增强顺铂对结肠癌细胞的抗癌作用仍不明确。本研究旨在探讨RA是否能增强顺铂对结肠癌细胞的细胞毒性及其潜在机制。分别使用磺酰罗丹明B（SRB）测定法、流式细胞术分析和碘化丙啶/膜联蛋白V染色评估细胞活力、细胞周期进程和细胞凋亡。采用蛋白质免疫印迹法分析信号通路。我们的研究结果表明，RA显著增强了对结肠癌细胞系DLD-1和LoVo的细胞活力抑制作用及细胞凋亡诱导作用。信号级联分析显示，RA和顺铂联合诱导DLD-1细胞中Bax和半胱天冬酶激活，同时下调Bcl-2、谷胱甘肽过氧化物酶4（GPX4）和溶质载体家族7成员11（SLC7A11）。此外，半胱天冬酶抑制剂和铁死亡抑制剂显著逆转了RA联合顺铂对细胞活力的抑制作用。总的来说，这些研究结果表明，RA增强了顺铂对结肠癌细胞的细胞毒性，这归因于其对细胞凋亡和铁死亡的促进作用。
