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

Tze Sing Huang, Chun Chung Lee, Yee Chao, Chih Hung Shu, Li Tzong Chen, Li Li Chen, Min Hsiung Chen, Chiou Chung Yuan, Jacqueline Whang-Peng

Research output: Contribution to journalArticle

56 Citations (Scopus)

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 lower than 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.

Original languageEnglish
Pages (from-to)997-1002
Number of pages6
JournalPharmaceutical Research
Volume16
Issue number7
DOIs
Publication statusPublished - Jan 1 1999
Externally publishedYes

Fingerprint

Podophyllotoxin
Etoposide
Refractory materials
Cells
Neoplasms
Cytotoxicity
Cell Line
Apoptosis
GL 331
Flow cytometry
Annexin A5
Ladders
Cell death
Neuroblastoma
Drug Resistance
Uterine Cervical Neoplasms
Assays
Lymphoma
Stomach
Flow Cytometry

Keywords

  • Apoptosis
  • Cytotoxicity
  • GL33 I
  • VP- 16

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

A novel podophyllotoxin-derived compound GL331 is more potent than its congener VP-16 in killing refractory cancer cells. / Huang, Tze Sing; Lee, Chun Chung; Chao, Yee; Shu, Chih Hung; Chen, Li Tzong; Chen, Li Li; Chen, Min Hsiung; Yuan, Chiou Chung; Whang-Peng, Jacqueline.

In: Pharmaceutical Research, Vol. 16, No. 7, 01.01.1999, p. 997-1002.

Research output: Contribution to journalArticle

Huang, Tze Sing ; Lee, Chun Chung ; Chao, Yee ; Shu, Chih Hung ; Chen, Li Tzong ; Chen, Li Li ; Chen, Min Hsiung ; Yuan, Chiou Chung ; Whang-Peng, Jacqueline. / A novel podophyllotoxin-derived compound GL331 is more potent than its congener VP-16 in killing refractory cancer cells. In: Pharmaceutical Research. 1999 ; Vol. 16, No. 7. pp. 997-1002.
@article{78dff55f7982412ca28046755a27a470,
title = "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 lower than 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.",
keywords = "Apoptosis, Cytotoxicity, GL33 I, VP- 16",
author = "Huang, {Tze Sing} and Lee, {Chun Chung} and Yee Chao and Shu, {Chih Hung} and Chen, {Li Tzong} and Chen, {Li Li} and Chen, {Min Hsiung} and Yuan, {Chiou Chung} and Jacqueline Whang-Peng",
year = "1999",
month = "1",
day = "1",
doi = "10.1023/A:1018971313256",
language = "English",
volume = "16",
pages = "997--1002",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "7",

}

TY - JOUR

T1 - A novel podophyllotoxin-derived compound GL331 is more potent than its congener VP-16 in killing refractory cancer cells

AU - Huang, Tze Sing

AU - Lee, Chun Chung

AU - Chao, Yee

AU - Shu, Chih Hung

AU - Chen, Li Tzong

AU - Chen, Li Li

AU - Chen, Min Hsiung

AU - Yuan, Chiou Chung

AU - Whang-Peng, Jacqueline

PY - 1999/1/1

Y1 - 1999/1/1

N2 - 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 lower than 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.

AB - 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 lower than 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.

KW - Apoptosis

KW - Cytotoxicity

KW - GL33 I

KW - VP- 16

UR - http://www.scopus.com/inward/record.url?scp=0032784679&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032784679&partnerID=8YFLogxK

U2 - 10.1023/A:1018971313256

DO - 10.1023/A:1018971313256

M3 - Article

C2 - 10450922

AN - SCOPUS:0032784679

VL - 16

SP - 997

EP - 1002

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 7

ER -