MTH-3 sensitizes oral cancer cells to cisplatin via regulating TFEB.

The Journal of pharmacy and pharmacology Pub Date : 2022-09-01 DOI:10.1093/jpp/rgac056

Shih-Chang Tsai, Jai-Sing Yang, Chi-Cheng Lu, Fuu-Jen Tsai, Yu-Jen Chiu, Sheng-Chu Kuo

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引用次数: 4

Abstract

Objectives: MTH-3, a curcumin derivative, exhibits improved water solubility. This study aims to elucidate the mechanisms underlying the anticancer effects of MTH-3 on human oral squamous cell carcinoma CAL27 cisplatin-resistant (CAR) cells.

Methods: To evaluate the biological functions of MTH-3 in CAR cells, flow cytometry, staining, and western blot analyses were used.

Key findings: MTH-3 reduced CAR cell viability and significantly induced autophagy in the presence of 10 and 20 μM MTH-3. Transcription factor EB was identified as the potential target of MTH-3. Autophagy-related proteins were upregulated after 24 h of MTH-3 incubation. MTH-3 treatment increased caspase-3 and caspase-9 enzyme activities. Mitochondrial membrane potential was decreased after MTH-3 treatment. MTH-3 triggered the intrinsic apoptotic pathway.

Conclusions: MTH-3 induces autophagy and apoptosis of CAR cells via TFEB. MTH-3 might be an effective pharmacological agent for treating oral cancer cells.

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MTH-3通过调节TFEB使口腔癌细胞对顺铂增敏。

目的:姜黄素衍生物MTH-3具有较好的水溶性。本研究旨在阐明MTH-3对人口腔鳞状细胞癌CAL27顺铂耐药(CAR)细胞的抗癌作用机制。方法:采用流式细胞术、染色、western blot等方法评价MTH-3在CAR细胞中的生物学功能。主要发现:MTH-3在10和20 μM的MTH-3存在下降低CAR细胞活力并显著诱导自噬。转录因子EB被确定为MTH-3的潜在靶点。MTH-3孵育24小时后，自噬相关蛋白上调。MTH-3处理增加了caspase-3和caspase-9酶活性。MTH-3处理后线粒体膜电位降低。MTH-3触发内在凋亡通路。结论:MTH-3通过TFEB诱导CAR细胞自噬和凋亡。MTH-3可能是治疗口腔癌细胞的有效药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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The Journal of pharmacy and pharmacology

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