Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis

Su-Ying Wen; Shang-Chuan Ng; Wen-Kun Ho; Han-Zhe Huang; Chih-Yang Huang; Wei-Wen Kuo

doi:10.1016/j.crtox.2023.100136

Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis

Curr Res Toxicol. 2023 Nov 11:5:100136. doi: 10.1016/j.crtox.2023.100136. eCollection 2023.

Authors

Su-Ying Wen^{1

2

3}, Shang-Chuan Ng^{4

5}, Wen-Kun Ho^{4

5}, Han-Zhe Huang^{4

5}, Chih-Yang Huang^{6

7

8

9

10}, Wei-Wen Kuo^{4

5}

Affiliations

¹ Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei, Taiwan.
² Department of Cosmetic Applications and Management, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
³ Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.
⁴ Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan.
⁵ Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, Taiwan.
⁶ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁷ Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
⁸ Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
⁹ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹⁰ Department of Biotechnology, Asia University, Taichung, Taiwan.

Abstract

Diallyl trisulfide (DATS), an organosulfide compound derived from garlic, is renowned for its potent antioxidant properties, particularly in countering the generation of reactive oxygen species (ROS). It has also gained recognition as a potential agent for preventing heart-related conditions. Doxorubicin (Dox), a commonly used chemotherapeutic drug, is known to induce severe cardiac complications by promoting ROS production. Therefore, it was imperative to investigate whether DATS possesses cardioprotective capabilities against Dox-induced cardiac apoptosis and elucidate the underlying mechanisms. In this study, we observed that the intracellular ROS levels and cardiac apoptosis were heightened in H9c2 cells exposed to Dox (1 μM). However, treatment with 10 μM DATS effectively mitigated the Dox-induced ROS generation and apoptotic signaling, concurrently activating the PI3K/Akt pathway. Notably, the anti-apoptotic effects of DATS were attenuated when PI3K siRNA and the LY294002 PI3K inhibitor were employed. Furthermore, the TUNEL assay results demonstrated a significant reduction in Dox-induced apoptosis with DATS treatment. In summary, our findings indicate that DATS can activate the PI3K/Akt pathway, reducing ROS production in cardiac cells exposed to Dox, and subsequently rescue cardiac cells from apoptosis.

Keywords: Cardiac apoptosis; Dially trisulfide; Doxorubicin; Reactive oxygen species.