Synthetic lethality in human bladder cancer cells by curcumin via concurrent Aurora A inhibition and autophagy induction

Ya Wen Fan, I. Ching Lu, Man Yuan Hsu, Wan Ting Kuo, Shan Ying Wu, Sheng Hui Lan, Pao Yuan Wang, Ching Ying Chen, Hsiao Sheng Liu, Chun Li Su*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

1 引文 斯高帕斯(Scopus)

摘要

Combination therapies to induce mixed-type cell death and synthetic lethality have the potential to overcome drug resistance in cancer. In this study, we demonstrated that the curcumin-enhanced cytotoxicity of cisplatin/carboplatin in combination with gemcitabine was associated with Aurora A suppression-mediated G2/M arrest, and thus apoptosis, as well as MEK/ERK-mediated autophagy in human bladder cancer cells. Animal study data confirmed that curcumin combined with cisplatin/gemcitabine reduced tumorigenesis of xenograft in mice and this phenomenon was associated with elevated expressions of p-ERK and reduced p-Aurora A in tumors. Gene analyses using data repositories further revealed that reduced Aurora A expression alone did not significantly elevate the sensitivity of human bladder carcinoma cells to these anticancer drugs. Unlike other major cancer types, human bladder urothelial carcinoma tissue coexpressed higher AURKA and lower MAP1LC3B than normal tissue, and reduced Aurora A and induction of autophagy have been clinically associated with a better prognosis in patients with early but not advanced stage bladder cancer. Therefore, our results suggest that treatment strategies can utilize the synthetic lethal pair to concurrently suppress oncogenic Aurora A and induce autophagy by coadministrating curcumin with anticancer drugs for early-stage bladder cancer with high expression of Aurora A.

原文英語
文章編號109438
期刊Journal of Nutritional Biochemistry
121
DOIs
出版狀態已發佈 - 2023 11月

ASJC Scopus subject areas

  • 內分泌學、糖尿病和代謝
  • 生物化學
  • 分子生物學
  • 營養與營養學
  • 臨床生物化學

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