Tumor-Inhibitory Effects of Zerumbone Against HT-29 Human Colorectal Cancer Cells. (September 2022)

• Record Type: Journal Article
• Authors: Memari, Fezzeh; Mirzavi, Farshad; Jalili‐Nik, Mohammad; Afshari, Amir R.; Ghorbani, Ahmad; Soukhtanloo, Mohammad
• Is Part Of: International journal of toxicology. Volume 41:Number 5(2022)
• Page Start: 402
• Page End: 411
• Publication Date: 2022-09
• Subjects: Zerumbone -- colorectal cancer -- HT-29 -- metastasis -- apoptosis; Toxicology -- Periodicals; 615.9005
• DOI: 10.1177/10915818221104417
• Languages: English
• ISSNs: 1091-5818

Abstract

Colorectal cancer (CRC) is the second cause of cancer-associated death globally. Recently, herbal medicinal products and, in particular, zerumbone have been widely studied and used for cancer treatment as they induce significant anti-cancer effects. However, there is limited information about the anti-cancer effects of zerumbone in CRC. Therefore, we aimed to investigate the in vitro anti-cancer effects of the zerumbone in CRC, focusing on cell apoptosis and migration. Anti-proliferative and anti-migratory effects of zerumbone on HT-29 cells were evaluated using MTT and scratch wound healing assay, respectively. Quantitative real-time PCR (qRT-PCR) was performed to determine the mRNA expression levels of migration and apoptosis-related genes. Apoptosis and cell cycle distribution were evaluated by flow cytometry. The intracellular level of reactive oxygen species (ROS) was measured using a ROS assay kit. Additionally, matrix metalloproteinase-2/-9 (MMP-2/-9) activity was determined using gelatin zymography. Zerumbone suppressed the viability of the HT-29 cells dose-dependently while having less cytotoxicity on normal NIH/3T3 cells. Zerumbone induced apoptosis in HT-29 cells and arrested the cell cycle in the G2/M phase. These effects were associated with alteration in the expression of apoptosis-related genes (up-regulation of Bax and down-regulation of Bcl-2 genes). Zerumbone also enhanced the generation of ROS in HT-29 cells. Furthermore, zerumbone significantly inhibited the migration of HT-29 cells and decreased MMP-2/-9 mRNA expression and activity. Our findings provide a potential use for zerumbone to induce apoptosis and suppress metastasis in HT-29 cells; thus, it could be developed as a promising natural agent for future CRC therapy.