Temozolomide abrogates the aggressiveness of urothelial carcinoma cells by enhancing senescence and depleting the side population

Kim,Na-Yon; Hwang,Sung-Hyun; Yang,Yeseul; Kim,Yongbaek

doi:10.3892/ol.2021.13106

Temozolomide abrogates the aggressiveness of urothelial carcinoma cells by enhancing senescence and depleting the side population

Authors:
- Na-Yon Kim
- Sung-Hyun Hwang
- Yeseul Yang
- Yongbaek Kim
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Affiliations: Laboratory of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea
Published online on: October 21, 2021 https://doi.org/10.3892/ol.2021.13106
Article Number: 845
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Patients with advanced urothelial carcinoma (UC) generally have poor prognoses due to therapeutic resistance. Furthermore, there are limited treatment options for advanced UC. Therefore, novel or effective chemotherapeutic agents are needed to improve patient survival. The present study was conducted to investigate the effect of temozolomide (TMZ) on UC cells so as to identify a potential method to overcome therapeutic resistance. TMZ is an alkylating agent with a target different from that of other anticancer drugs used to treat UC, such as cisplatin. TMZ enhanced the autophagic response and senescence, which was mediated via the p53 and p21 pathways. Inhibiting the autophagic response using chloroquine synergistically augmented the cytotoxic effect of TMZ on UC cells. TMZ significantly reduced the invasiveness of UC cells. Notably, the abundance of side population fraction was also significantly reduced following TMZ treatment. Considering that side population fraction is known to confer therapeutic resistance, it is noteworthy that the TMZ treatment markedly decreased side population fraction. Altogether, TMZ may have the potential to be applied as a part of an alternative treatment strategy to reduce the malignancy of UC cells.

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