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

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.

• Authors: T S Huang, C C Lee, Y Chao, C H Shu, L T Chen, L L Chen, M H Chen, C C Yuan, J Whang-Peng
• Journal: Pharmaceutical research (Pharm Res) Vol. 16 Issue 7 Pg. 997-1002 (Jul 1999) ISSN: 0724-8741 [Print] United States
• PMID: 10450922 (Publication Type: Comparative Study, Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents, Phytogenic
• GL 331
• Etoposide
• Podophyllotoxin

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis, metabolism)
• Antineoplastic Agents, Phytogenic (toxicity)
• Apoptosis (drug effects)
• Cell Death (drug effects)
• Drug Resistance, Multiple
• Drug Screening Assays, Antitumor
• Etoposide (analogs & derivatives, pharmacology, toxicity)
• Humans
• Neoplasms (drug therapy, metabolism)
• Podophyllotoxin (analogs & derivatives, toxicity)
• Tumor Cells, Cultured