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Radiation Oncology

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Open Access 01-12-2011 | Research

Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells

Authors: Chia-Yuan Liu, Hsun-Shuo Chang, Ih-Sheng Chen, Chih-Jen Chen, Ming-Ling Hsu, Shu-Ling Fu, Yu-Jen Chen

Published in: Radiation Oncology | Issue 1/2011

Abstract

Purpose

This work aimed to investigate the effect of costunolide, a sesquiterpene lactone isolated from Michelia compressa, on cell cycle distribution and radiosensitivity of human hepatocellular carcinoma (HCC) cells.

Methods

The assessment used in this study included: cell viability assay, cell cycle analysis by DNA histogram, expression of phosphorylated histone H3 (Ser 10) by flow cytometer, mitotic index by Liu's stain and morphological observation, mitotic spindle alignment by immunofluorescence of alpha-tubulin, expression of cell cycle-related proteins by Western blotting, and radiation survival by clonogenic assay.

Results

Our results show that costunolide reduced the viability of HA22T/VGH cells. It caused a rapid G2/M arrest at 4 hours shown by DNA histogram. The increase in phosphorylated histone H3 (Ser 10)-positive cells and mitotic index indicates costunolide-treated cells are arrested at mitosis, not G2, phase. Immunofluorescence of alpha-tubulin for spindle formation further demonstrated these cells are halted at metaphase. Costunolide up-regulated the expression of phosphorylated Chk2 (Thr 68), phosphorylated Cdc25c (Ser 216), phosphorylated Cdk1 (Tyr 15) and cyclin B1 in HA22T/VGH cells. At optimal condition causing mitotic arrest, costunolide sensitized HA22T/VGH HCC cells to ionizing radiation with sensitizer enhancement ratio up to 1.9.

Conclusions

Costunolide could reduce the viability and arrest cell cycling at mitosis in hepatoma cells. Logical exploration of this mitosis-arresting activity for cancer therapeutics shows costunolide enhanced the killing effect of radiotherapy against human HCC cells.

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Title: Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells
Authors: Chia-Yuan Liu
Hsun-Shuo Chang
Ih-Sheng Chen
Chih-Jen Chen
Ming-Ling Hsu
Shu-Ling Fu
Yu-Jen Chen
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2011
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/1748-717X-6-56

At a glance: The STEP trials

Springer Medicine

Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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