2. Academic Validation
  3. The 3-deoxysappanchalcone induces ROS-mediated apoptosis and cell cycle arrest via JNK/p38 MAPKs signaling pathway in human esophageal cancer cells

The 3-deoxysappanchalcone induces ROS-mediated apoptosis and cell cycle arrest via JNK/p38 MAPKs signaling pathway in human esophageal cancer cells

  • Phytomedicine. 2021 Jun:86:153564. doi: 10.1016/j.phymed.2021.153564.
Ah-Won Kwak 1,  Myeoung-Jun Lee 1,  Mee-Hyun Lee 2,  Goo Yoon 1,  Seung-Sik Cho 1,  Jung-Il Chae 3,  Jung-Hyun Shim 4
Affiliations

Affiliations

  • 1 Department of Pharmacy, College of Pharmacy, Mokpo National University, Jeonnam 58554, Republic of Korea.
  • 2 College of Korean Medicine, Dongshin University, Naju, Jeonnam 58245, Republic of Korea.
  • 3 Department of Dental Pharmacology, School of Dentistry, Jeonbuk National University, Jeonju 54896, Republic of Korea. Electronic address: [email protected].
  • 4 Department of Pharmacy, College of Pharmacy, Mokpo National University, Jeonnam 58554, Republic of Korea; The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450008, PR China; Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam 58554, Republic of Korea. Electronic address: [email protected].
PMID: 33895649 DOI: 10.1016/j.phymed.2021.153564
Abstract

Background: The 3-deoxysappanchalcone (3-DSC), a chemical separated from Caesalpinia sappan L, has been substantiated to display anti-inflammatory, anti-influenza, and anti-allergy activities according to previous studies. However, the underlying mechanisms of action on esophageal Cancer remain unknown.

Purpose: The present research aims to survey the action mechanisms of 3-DSC in esophageal squamous cell carcinoma (ESCC) cells in vitro.

Methods: Evaluation of cytotoxicity was determined by MTT tetrazolium salt assay and soft agar assay. Cell cycle distribution, Apoptosis induction, Reactive Oxygen Species (ROS) generation, mitochondrial membrane potential (MMP), and multi-caspases activity were appreciated by Muse™ Cell Analyzer. The expressions of cell cycle- and apoptosis-related proteins were presented using Western blotting.

Results: 3-DSC blocked cell growth and colony formation ability in a concentration-dependent manner and invoked Apoptosis, G2/M cell cycle arrest, ROS production, MMP depolarization, and multi-caspase activity. Furthermore, Western blotting results demonstrated that 3-DSC upregulated the expression of phospho (p)-c-jun NH2-terminal kinases (JNK), p-p38, cell cycle regulators, pro-apoptotic proteins, and endoplasmic reticulum (ER) stress-related proteins whereas downregulated the levels of anti-apoptotic proteins and cell cycle promoters. The effects of 3-DSC on ROS induction were counteracted by pretreatment with N-acetyl-L-cysteine (NAC). Also, our results indicated that p38 (SB203580) and JNK (SP600125) inhibitor slightly inhibited 3-DSC-induced Apoptosis. These results showed that 3-DSC-related G2/M phase cell cycle arrest and Apoptosis by JNK/p38 MAPK signaling pathway in ESCC cells were mediated by ROS.

Conclusion: ROS generation by 3-DSC in Cancer cells could be an attractive strategy for Apoptosis of Cancer cells by inducing cell cycle arrest, ER stress, MMP loss, multi-caspase activity, and JNK/p38 MAPK pathway. Our findings suggest that 3-DSC is a promising novel therapeutic candidate for both prevention and treatment of esophageal Cancer.

Keywords

3-deoxysappanchalcone; Cell cycle arrest; Esophageal squamous cell carcinoma; Reactive oxygen species; c-jun NH2-terminal kinases; p38.

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