Diallyl trisulfide, a H<sub>2</sub>S donor, inhibits cell growth of human papillary thyroid carcinoma KTC‐1 cells through a positive feedback loop between H<sub>2</sub>S and cystathionine‐gamma‐lyase
Shichen Xu, Jie Pan, Xian Cheng, Jiangxia Zheng, Xiaowen Wang, Haixia Guan, Huixin Yu, Jiandong Bao, Li Zhang
Abstract
Diallyl trisulfide (DATS), derived from garlic, is a well‐known hydrogen sulfide (H 2 S) donor. H 2 S has recently emerged as a novel gasotransmitter involved in the regulation of cancer progression. The present study demonstrated that DATS along with other two H 2 S donors, NaHS and GYY4137, significantly inhibited papillary thyroid carcinoma KTC‐1 cells growth. DATS treatment triggered a rapid H 2 S generation within 5 min in KTC‐1 cells. Iodoacetamide, a potent thiol blocker reagent, partially rescued the cell membrane damage and ultimate cell death induced by DATS, indicating H 2 S contributed to the apoptosis‐inducing efficacy of DATS on thyroid cancer cells. Specifically, DATS treatment significantly upregulated the expression and enzymatic activity of cystathionine gamma‐lyase (CTH), one of H 2 S‐producing enzymes, which was responsible for endogenous H 2 S generation. After DATS treatment, H 2 S quickly permeated cell membranes and activated NF‐κΒ/p65 signaling pathway in KTC‐1 cells. Nuclear translocated NF‐κB bound to the promoter of CTH to enhance its transcription. These evidences proved that exogenous H 2 S elevated CTH expression. CTH, in turn, catalytically generated a much higher level of endogenous H 2 S. This positive feedback sustained excess H 2 S production, which resulted in PTC cells growth inhibition. These findings may shed light on the development of novel H 2 S‐based antitumor agents.