Griseofulvin potentiates antitumorigenesis effects of nocodazole through induction of apoptosis and G2/M cell cycle arrest in human colorectal cancer cells

Yuan Soon Ho, Jiing Shium Duh, Jiiang Huei Jeng, Ying Jan Wang, Yu Chih Liang, Chien Huang Lin, Chia Jen Tseng, Cheng Fei Yu, Rong Jane Chen, Jen Kun Lin

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

In this study, we demonstrate that apoptosis and G2/M cell cycle arrest were easily induced by treatment with the oral-antifungal agent, griseofulvin (GF). The mechanisms of GF-induced G2/M arrest were characterized as (a) induction of abnormal mitotic spindle formation, (b) elevation of cyclin B1/cdc2 kinase activity and (c) down-regulation of myt-I protein expression. On the other hand, caspase 3 activation, Bcl-2 hyperphosphorylation and inhibition of the normal function of Bcl-2 associated with Bax were demonstrated to be the mechanisms of GF-induced apoptosis. DNA fragmentation and flow cytometry analyses demonstrated that combined treatment of GF with the cancer chemotherapeutic agent, nocodazole (ND), strongly potentiates the apoptotic effect and arrest of the G2/M cell cycle in 5 types of human cancer cells, but not in normal human keratinocytes (#76 KhGH). The combined treatment of GF and ND triggered the polymerization of purified tubulin in HT 29 but not in #76 KhGH cells. To further confirm these observations, the therapeutic efficacy was further examined in vivo by treating athymic mice bearing COLO 205 tumor xenografts, with GF (50 mg/kg), ND (5 mg/kg) or GF + ND. Combined treatment of GF and ND significantly enhanced the effect of ND, and led to cessation of tumor growth. These results suggest that chemotherapeutic agents (such as ND) administered in the presence of GF might provide a novel therapy for colorectal cancer.

Original languageEnglish
Pages (from-to)393-401
Number of pages9
JournalInternational Journal of Cancer
Volume91
Issue number3
DOIs
Publication statusPublished - Feb 1 2001

Fingerprint

G2 Phase Cell Cycle Checkpoints
Nocodazole
Griseofulvin
Colorectal Neoplasms
Apoptosis
Neoplasms
Cyclin B1
Spindle Apparatus
Antifungal Agents
DNA Fragmentation
Tubulin
Keratinocytes
Heterografts
Nude Mice
Caspase 3
Polymerization
Flow Cytometry
Phosphotransferases
Down-Regulation

Keywords

  • Apoptosis
  • Bcl-2
  • G2/M arrest
  • Griseofulvin
  • Microtubule

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Griseofulvin potentiates antitumorigenesis effects of nocodazole through induction of apoptosis and G2/M cell cycle arrest in human colorectal cancer cells. / Ho, Yuan Soon; Duh, Jiing Shium; Jeng, Jiiang Huei; Wang, Ying Jan; Liang, Yu Chih; Lin, Chien Huang; Tseng, Chia Jen; Yu, Cheng Fei; Chen, Rong Jane; Lin, Jen Kun.

In: International Journal of Cancer, Vol. 91, No. 3, 01.02.2001, p. 393-401.

Research output: Contribution to journalArticle

Ho, Yuan Soon ; Duh, Jiing Shium ; Jeng, Jiiang Huei ; Wang, Ying Jan ; Liang, Yu Chih ; Lin, Chien Huang ; Tseng, Chia Jen ; Yu, Cheng Fei ; Chen, Rong Jane ; Lin, Jen Kun. / Griseofulvin potentiates antitumorigenesis effects of nocodazole through induction of apoptosis and G2/M cell cycle arrest in human colorectal cancer cells. In: International Journal of Cancer. 2001 ; Vol. 91, No. 3. pp. 393-401.
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AU - Duh, Jiing Shium

AU - Jeng, Jiiang Huei

AU - Wang, Ying Jan

AU - Liang, Yu Chih

AU - Lin, Chien Huang

AU - Tseng, Chia Jen

AU - Yu, Cheng Fei

AU - Chen, Rong Jane

AU - Lin, Jen Kun

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