Format

Send to

Choose Destination
See comment in PubMed Commons below
Pharm Res. 1999 Jul;16(7):997-1002.

A novel podophyllotoxin-derived compound GL331 is more potent than its congener VP-16 in killing refractory cancer cells.

Author information

1
Cooperative Laboratory, Cancer Research Division, National Health Research Institutes, Taipei, Taiwan, Republic of China. tshuang@nhri.org.tw

Abstract

PURPOSE:

GL331 is a new homolog of VP-16, and has demonstrated more efficacious anti-cancer activity in both the in vitro and in vivo lymphoma systems. To extensively explore GL331's clinical value, we furthermore evaluate the cytotoxicity and apoptosis-inducing activity of GL331 in several human cell lines from cancers that are not normally treated with VP-16.

METHODS:

By MTT and clonogenic survival assays, the cytotoxicities of GL331 and VP-16 were evaluated in a variety of cell lines including nasopharyngeal, hepatocellular, gastric, colon, cervical, and neuroblastoma cancer types. Western blot analysis was performed to detect the MDR-1 level in these cell lines. By Annexin V-staining flow cytometry and detection of DNA ladders, the apoptosis-inducing activities of GL331 and VP-16 were also evaluated.

RESULTS:

GL331 showed more efficacy than its congener VP-16 in killing cancer cells. The estimated ID50 of GL331 were 2.5 to 17-fold lowerthan those of VP-16. GL331 possessed more cell-killing activity even in MDR-1-overexpressing cell lines such as HCC36 and SW620. Its higher cytotoxicity could be attributed by the elevated ability to induce apoptotic cell death.

CONCLUSION:

GL331's overriding drug resistance and higher cancer cell-killing activity suggest its superiority in clinical cancer therapy.

PMID:
10450922
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Support Center