Inhibition of hedgehog signaling reduces the side population in human malignant mesothelioma cell lines.

Abstract

Deregulation of crucial embryonic pathways, including hedgehog signaling, has been frequently implicated in a variety of human cancers and is emerging as an important target for anticancer therapy. This study evaluated the potential anticancer effects of cyclopamine, a chemical inhibitor of hedgehog signaling, in human malignant mesothelioma (HMM) cell lines. Cyclopamine treatment significantly decreased the proliferation of HMM cells by promoting apoptosis and shifting the cell cycle toward dormant phase. The clonogenicity and mobility of HMM cells were significantly decreased by cyclopamine treatment. Treatment of HMM cells with cyclopamine significantly reduced the abundance of side population cells, which were measured using an assay composed of Hoechst 33342 dye staining and subsequent flow cytometry. Furthermore, the expression levels of stemness-related genes were significantly affected by cyclopamine treatment. Taken together, the present study showed that targeting hedgehog signaling could reduce a more aggressive subpopulation of the cancer cells, suggesting an alternative approach for HMM therapy.

• Authors: H-A Kim, M-C Kim, N-Y Kim, Y Kim
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 22 Issue 8 Pg. 387-95 (Aug 2015) ISSN: 1476-5500 [Electronic] England
• PMID: 26206198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Hedgehog Proteins
• Veratrum Alkaloids
• tomatidine
• Tomatine
• cyclopamine

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Hedgehog Proteins (antagonists & inhibitors, metabolism)
• Humans
• Lung Neoplasms (drug therapy, genetics, metabolism, pathology)
• Mesothelioma (drug therapy, genetics, metabolism, pathology)
• Mesothelioma, Malignant
• Molecular Targeted Therapy (methods)
• Signal Transduction (drug effects)
• Tomatine (analogs & derivatives, pharmacology)
• Veratrum Alkaloids (pharmacology)