Apoptosis induced by one new podophyllotoxin glucoside in human carcinoma cells.

Abstract

4-Demethyl-picropodophyllotoxin 7'-O-beta-D-glucopyranoside (4DPG), a new podophyllotoxin glucoside, was isolated from the rhizomes of Sinopodophyllum emodi (Wall.) Ying and showed cytotoxic effects in human carcinoma cells. Among the target cells (HeLa, A2 and SH-SY5Y), the cytotoxic effects of 4DPG showed dose- and time-dependency. Furthermore, the cervical carcinoma cell line, HeLa, was more sensitive to 4DPG. Flow cytometric analysis demonstrated the presence of apoptotic cells with low DNA content, a decrease of cell population at the G1 phase, and a concomitant increase of cell population at the G2/M phase. 4DPG also caused DNA fragmentation in HeLa cells. Treatment with 0.1 microM 4DPG increased p53 expression and Bax/Bcl-2 ratio in HeLa cells, as well as in A2 cells. These results suggested that 4DPG-induced apoptosis might be through a p53-dependent pathway.

• Authors: Qiu-Ying Zhang, Min Jiang, Chang-Qi Zhao, Miao Yu, Hui Zhang, Yu-Jia Ding, Yong-Gong Zhai
• Journal: Toxicology (Toxicology) Vol. 212 Issue 1 Pg. 46-53 (Aug 15 2005) ISSN: 0300-483X [Print] Ireland
• PMID: 15923073 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-demethyl-picropodophyllotoxin 7'-O-glucopyranoside
• Antineoplastic Agents, Phytogenic
• Glucosides
• Plant Extracts
• Podophyllotoxin

Topics

• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Apoptosis (drug effects, physiology)
• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• Dose-Response Relationship, Drug
• Glucosides (isolation & purification, pharmacology)
• HeLa Cells
• Humans
• Plant Extracts (chemistry, isolation & purification, pharmacology)
• Podophyllotoxin (analogs & derivatives, chemistry, isolation & purification, pharmacology)
• Podophyllum
• Rhizome