Heme Oxygenase-1 is a Key Molecule Underlying Differential Response of TW-37-Induced Apoptosis in Human Mucoepidermoid Carcinoma Cells.

Abstract

TW-37 is a small-molecule inhibitor of Bcl-2 family proteins, which can induce anti-cancer activities in various types of cancer. In the current study, we investigated the potential molecular mechanism underlying the differential response to TW-37-induced apoptosis in two human mucoepidermoid carcinoma (MEC) cell lines. The differential response and underlying molecular mechanism of human MEC cells to TW-37 was evaluated by trypan blue exclusion assay, western blotting, 4', 6-diamidino-2-phenylindole staining, annexin V/propidium iodide double staining, analysis of the sub-G1 population, human apoptosis array, and measurements of intracellular reactive oxygen species (ROS). TW-37 decreased cell viability and induced apoptosis in YD-15 cells, but not in MC3 cells. Proteome profiling using a human apoptosis array revealed four candidate proteins and of these, heme oxygenase-1 (HO-1) was mainly related to the differential response to TW-37 of YD-15 and MC3 cells. TW-37 also led to a significant increase in intracellular levels of ROS in YD-15 cells, which is associated with apoptosis induction. The ectopic expression of HO-1 recovered YD-15 cells from TW-37-induced apoptosis by reducing intracellular levels of ROS. The expression of HO-1 was reduced through both transcriptional and post-translational modification during TW-37-mediated apoptosis. We conclude that HO-1 is a potential indicator to estimate response to TW37-induced apoptosis in human MEC.

• Authors: In-Hyoung Yang, Chi-Hyun Ahn, Nam-Pyo Cho, Bohwan Jin, WonWoo Lee, Yun Chan Jung, Seong Doo Hong, Ji-Ae Shin, Sung-Dae Cho
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 24 Issue 9 (May 01 2019) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 31052354 (Publication Type: Journal Article)

Chemical References

• Benzamides
• Reactive Oxygen Species
• Sulfones
• TW-37 compound
• HMOX1 protein, human
• Heme Oxygenase-1

Topics

• Benzamides (pharmacology)
• Carcinoma, Mucoepidermoid (drug therapy, genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Heme Oxygenase-1 (genetics, metabolism)
• Humans
• Protein Processing, Post-Translational (drug effects)
• Proteomics (methods)
• Reactive Oxygen Species (metabolism)
• Sulfones (pharmacology)