Antibladder Cancer Effects of Excavatolide C by Inducing Oxidative Stress, Apoptosis, and DNA Damage In Vitro

Che-Wei Yang; Tsu-Ming Chien; Chia-Hung Yen; Wen-Jeng Wu; Jyh-Horng Sheu; Hsueh-Wei Chang

doi:10.3390/ph15080917

Antibladder Cancer Effects of Excavatolide C by Inducing Oxidative Stress, Apoptosis, and DNA Damage In Vitro

Pharmaceuticals (Basel). 2022 Jul 24;15(8):917. doi: 10.3390/ph15080917.

Authors

Che-Wei Yang¹, Tsu-Ming Chien^{2

3

4}, Chia-Hung Yen¹, Wen-Jeng Wu^{2

3

4}, Jyh-Horng Sheu^{5

6}, Hsueh-Wei Chang^{7

8

9}

Affiliations

¹ Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
² Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
³ Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.
⁴ Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
⁵ Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
⁶ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan.
⁷ Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁸ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁹ Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Abstract

Excavatolide C (EXCC) is a bioactive compound derived from the gorgonian octocoral Briareum excavatum, and its anticancer effects are rarely addressed, particularly for bladder cancer. This investigation aimed to explore the potential impacts of EXCC on inhibiting the proliferation of three kinds of bladder cancer cells (5637, BFTC905, and T24). EXCC inhibits bladder cancer cell proliferation based on 48 h ATP assay. This antiproliferation function is validated to be oxidative stress dependent. Cellular and mitochondrial oxidative stresses were upregulated by EXCC, accompanied by depleting glutathione and mitochondrial membrane potential. These antiproliferation and oxidative stress events were suppressed by N-acetylcysteine (NAC), indicating that EXCC has an oxidative stress-regulating function for antiproliferation of bladder cancer cells. Oxidative stress-related responses such as apoptosis, caspase activation, and DNA damage were upregulated by EXCC and reverted by NAC. Taken together, the antiproliferation function of EXCC provides a potential treatment against bladder cancer cells via oxidative stress modulation.

Keywords: DNA damage; apoptosis; bladder cancer; oxidative stress; soft coral.

Abstract

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