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

H-A Kim1, M-C Kim1, N-Y Kim1

  • 11] Laboratory of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea [2] BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.

Cancer Gene Therapy
|July 25, 2015
PubMed

Insights

Cyclopamine, a hedgehog signaling inhibitor, reduced human malignant mesothelioma cell growth by inducing apoptosis and cell cycle arrest. This targeted therapy also decreased cancer stem cell populations, offering a novel approach for mesothelioma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Hedgehog signaling pathway deregulation is linked to various human cancers.
  • This pathway is an emerging therapeutic target for anticancer strategies.
  • Malignant mesothelioma (HMM) is an aggressive cancer with limited treatment options.

Purpose of the Study:

  • To investigate the anticancer effects of cyclopamine, a hedgehog signaling inhibitor, on human malignant mesothelioma (HMM) cell lines.
  • To determine if targeting hedgehog signaling can impact HMM cell proliferation, apoptosis, cell cycle, clonogenicity, mobility, and stemness characteristics.

Main Methods:

  • Human malignant mesothelioma (HMM) cell lines were treated with cyclopamine.
  • Cell proliferation, apoptosis, and cell cycle distribution were assessed.
  • Clonogenicity and cell mobility assays were performed.
  • Side population cells were identified and quantified using Hoechst 33342 dye staining and flow cytometry.
  • Expression levels of stemness-related genes were analyzed.

Main Results:

  • Cyclopamine significantly inhibited HMM cell proliferation.
  • Treatment promoted apoptosis and induced cell cycle arrest in HMM cells.
  • Clonogenicity and mobility of HMM cells were significantly reduced.
  • Cyclopamine decreased the abundance of side population cells, indicative of cancer stem cells.
  • Expression of stemness-related genes was significantly altered by cyclopamine treatment.

Conclusions:

  • Targeting the hedgehog signaling pathway with cyclopamine demonstrates significant anticancer effects in human malignant mesothelioma.
  • Cyclopamine reduces aggressive cancer cell subpopulations, including cancer stem cells.
  • This study suggests that targeting hedgehog signaling is a promising therapeutic strategy for malignant mesothelioma.

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