Antineoplastic effects of deoxypodophyllotoxin, a potent cytotoxic agent of plant origin, on glioblastoma U-87 MG and SF126 cells.

Abstract

BACKGROUND:

Deoxypodophyllotoxin (DPT) is a semi-synthetic compound derived from the extract of Dysosma versipellis (Hance) M. Cheng, one of the most popular Chinese herbal medicines. The present study evaluates the in vitro cytotoxicity of DPT on a wide panel of human cancer cell lines and investigates its molecular mechanism of action on high grade glioma U-87 MG and SF126 cells.

METHODS:

The growth inhibitory effect of DPT on different types of human cancer cells was measured by the Cell Counting Kit-8 (CCK-8) assay. For the elucidation of the nature of the cellular response to DPT-treatment; flow cytometry-based assays, light and fluorescent microscopy, caspase colorimetric and inhibition assays, and Western blot analysis were performed.

RESULTS:

Our data show that DPT possesses a potent growth-inhibitory action, with IC50 values in nanomolar ranges. Cell cycle analysis revealed G2/M phase arrest in a dose- and time-dependent manner before cell death occurred. Additional studies indicated that DPT induced G2 arrest in U-87 MG cells by decreasing the expression of Cdc2, cyclin B1, and Cdc25C proteins. In contrast, DPT failed to down-regulate these cell cycle regulatory molecules in SF126 glioblastoma cells and stopped the cell cycle at M phase. Interestingly, morphological changes and biochemical markers such as phosphatydylserine externalization, DNA fragmentation, and caspase activation, confirmed that DPT-treatment resulted in an induction of apoptosis in both examined cell lines via caspase-dependent pathways.

CONCLUSIONS:

Taken together, our data demonstrated that DPT possesses a potent in vitro cytotoxic activity and exerts its effect via G2/M arrest and apoptosis.

• Authors: Mounia Guerram, Zhen-Zhou Jiang, Lixin Sun, Xiong Zhu, Lu-Yong Zhang
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 67 Issue 2 Pg. 245-52 (Apr 2015) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 25712646 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Cyclin B1
• Drugs, Chinese Herbal
• deoxypodophyllotoxin
• CDC2 Protein Kinase
• CDK1 protein, human
• Cyclin-Dependent Kinases
• CDC25C protein, human
• cdc25 Phosphatases
• Caspases
• Podophyllotoxin

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• CDC2 Protein Kinase
• Caspases (metabolism)
• Cell Count
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cyclin B1 (biosynthesis)
• Cyclin-Dependent Kinases (biosynthesis)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Drugs, Chinese Herbal
• Glioblastoma (pathology)
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Podophyllotoxin (analogs & derivatives, pharmacology)
• cdc25 Phosphatases (biosynthesis)