Novel dihydroartemisinin derivative Mito-DHA5 induces apoptosis associated with mitochondrial pathway in bladder cancer cells

Linfan Xiao; Cangcang Xu; Peiyu Lin; Lingli Mu; Xiaoping Yang

doi:10.1186/s40360-021-00542-6

Novel dihydroartemisinin derivative Mito-DHA₅ induces apoptosis associated with mitochondrial pathway in bladder cancer cells

BMC Pharmacol Toxicol. 2022 Jan 20;23(1):10. doi: 10.1186/s40360-021-00542-6.

Authors

Linfan Xiao¹, Cangcang Xu², Peiyu Lin¹, Lingli Mu³, Xiaoping Yang⁴

Affiliations

¹ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China.
² Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China. xucangcang@hunnu.edu.cn.
³ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China. moulingli@sina.com.
⁴ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China. Xiaoping.Yang@hunnu.edu.cn.

Abstract

Background: Bladder cancer is the second most common genitourinary malignancy and the eleventh most common cancer worldwide. Dihydroartemisinin (DHA), a first-line antimalarial drug, has been found to have potent antitumor activity. In our previous study, a novel dihydroartemisinin derivative Mito-DHA₅ synthesized in our laboratory has a stronger anti-tumor activity than DHA. In this study, we investigated the apoptotic effect of Mito-DHA₅ on bladder cancer T24 cells and molecular mechanisms underlying.

Methods: Antitumor activity in vitro was evaluated by MTT, wound healing and cloning formation assays. Mitochondrial membrane potential (MMP) was detected by JC-1 probe and ROS levels were measured by specific kit. The expression of caspase-3, cleaved-caspase3, mitochondrial Cyt-C, Bcl-2, Bax and PARP in T24 cells was evaluated by Western blotting.

Results: The results showed that Mito-DHA₅ reduced cell viability with an IC₅₀ value of 3.2 µM and induced T24 cell apoptosis in a dose-dependent manner, increased the production of ROS and decreased MMP. Mito-DHA₅ could down-regulate the expression of Bcl-2, mitochondrial Cyt-C, Caspase-3, PARP and up-regulate the expression of Bax and cleaved Caspase-3.

Conclusions: These data suggested that Mito-DHA₅ had a potent inhibitory effect on T24 bladder cancer cell growth and induced these cells apoptosis associated with mitochondrial pathway.

Keywords: Apoptosis; Bladder cancer; Dihydroartemisinin derivative; MMP; ROS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects*
Artemisinins / pharmacology*
Caspase 3 / metabolism
Cell Line, Tumor
Cell Proliferation
Humans
Membrane Potential, Mitochondrial
Mitochondria*
Reactive Oxygen Species / metabolism
Urinary Bladder Neoplasms* / drug therapy
Urinary Bladder Neoplasms* / pathology

Substances

Artemisinins
Reactive Oxygen Species
artenimol
Caspase 3