Open Access

Germacrone induces caspase‑3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis

  • Authors:
    • Xinfeng Sun
    • Xin Zhong
    • Wenfeng Ma
    • Wenxing Feng
    • Qi Huang
    • Mengqing Ma
    • Minling Lv
    • Rui Hu
    • Zhiyi Han
    • Jing Li
    • Xiaozhou Zhou
  • View Affiliations

  • Published online on: May 20, 2022     https://doi.org/10.3892/etm.2022.11383
  • Article Number: 456
  • Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer is a highly lethal malignancy. Despite considerable efforts made in recent years, the prognosis of patients with liver cancer remains poor. Curcuma zedoaria (known as Ezhu in Chinese) is widely prescribed in traditional Chinese medicine. Germacrone (GM) is a sesquiterpene constituent derived from the essential oil of Ezhu, and exerts anti‑carcinogenic effects by inducing apoptosis in various cancer cells. The present study investigated the potential mechanism of GM in HepG2 cells. Cell Counting Kit‑8, colony‑formation and lactate dehydrogenase‑release assays, as well as cell death assays using flow cytometry, were performed to evaluate HepG2 cell proliferation following GM treatment. HepG2 cells were transfected with caspase‑3 small interfering RNA and then treated with GM. Caspase‑3 expression levels were determined by reverse transcription‑quantitative PCR and western blotting. The present study showed that GM inhibited the growth of HepG2 cells and induced the proteolytic cleavage of caspase 3, with concomitant cleavage of gasdermin E (GSDME), by markedly increasing the production of reactive oxygen species (ROS). This led to caspase 3‑dependent cleavage of GSDME, thereby promoting pyroptosis in HepG2 cells. However, these changes were rescued by ROS scavengers, such as N‑acetylcysteine. Furthermore, GM inhibited tumor growth by promoting the cleavage of caspase 3 and GSDME in HepG2 cell xenograft models. These results indicated that GM induced GSDME‑dependent pyroptosis through caspase 3 activation, at least in part, by damaging the mitochondria and enhancing ROS production, thereby supporting the possible development of GM as a candidate for the prevention and treatment of liver cancer.
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July-2022
Volume 24 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Sun X, Zhong X, Ma W, Feng W, Huang Q, Ma M, Lv M, Hu R, Han Z, Li J, Li J, et al: Germacrone induces caspase‑3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis. Exp Ther Med 24: 456, 2022
APA
Sun, X., Zhong, X., Ma, W., Feng, W., Huang, Q., Ma, M. ... Zhou, X. (2022). Germacrone induces caspase‑3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis. Experimental and Therapeutic Medicine, 24, 456. https://doi.org/10.3892/etm.2022.11383
MLA
Sun, X., Zhong, X., Ma, W., Feng, W., Huang, Q., Ma, M., Lv, M., Hu, R., Han, Z., Li, J., Zhou, X."Germacrone induces caspase‑3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis". Experimental and Therapeutic Medicine 24.1 (2022): 456.
Chicago
Sun, X., Zhong, X., Ma, W., Feng, W., Huang, Q., Ma, M., Lv, M., Hu, R., Han, Z., Li, J., Zhou, X."Germacrone induces caspase‑3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis". Experimental and Therapeutic Medicine 24, no. 1 (2022): 456. https://doi.org/10.3892/etm.2022.11383