BPR0C261 is a novel orally active antitumor agent with antimitotic and anti-angiogenic activities

Chih Bo Hu, Ching Ping Chen, Teng Kuang Yeh, Jen Shin Song, Chi Yen Chang, Jiunn Jye Chuu, Fei Feng Tung, Pei Yin Ho, Tung Wei Chen, Chi Hung Lin, Min Hsien Wang, Kai Yen Chang, Chen Lung Huang, Heng Liang Lin, Wen Tai Li, Der Ren Hwang, Jyh Haur Chern, Ling Ling Hwang, Jang Yang Chang, Yu Sheng ChaoChiung Tong Chen

研究成果: 雜誌貢獻文章

8 引文 (Scopus)

摘要

BPR0C261 is a synthetic small molecule compound cytotoxic against human cancer cells and active prolonging the lifespan of leukemia mice. In the present study, we further investigated the mechanisms of its anticancer action and found that BPR0C261 inhibited microtubule polymerization through interacting with the colchicine binding sites on tubulins, disrupted microtubule arrangement and caused cell cycle arrest at G2/M phase in cancer cells. BPR0C261 also inhibited the clonogenic growths of cancer cells and showed cytotoxicity against human cervical cancer cells of multidrug-resistant phenotype. In addition, BPR0C261 concentration-dependently inhibited the proliferation and migration of HUVECs and disrupted the endothelial capillary-like tube formations in HUVEC and rat aorta ring cultures. Given orally, BPR0C261 inhibited angiogenesis in s.c. implanted Matrigel plugs in mice. Notably, its IC50 values against the endothelial cell growths were approximately 10-fold lower than those against the cancer cells. It was found orally absorbable in mice and showed a good oral bioavailability (43%) in dogs. BPR0C261 permeated through the human intestinal Caco-2 cell monolayer, suggesting oral availability in humans. Orally absorbed BPR0C261 distributed readily into the s.c. xenografted tumors in nude mice in which the tumor tissue levels of BPR0C261 were found oral dose-dependent. BPR0C261 showed in vivo activities against human colorectal, gastric, and nasopharyngeal tumors in nude mice. Most interestingly, the combination of BPR0C261 plus cisplatin synergistically prolonged the lifespans of mice inoculated with murine leukemia cells. Thus, BPR0C261 is a novel orally active tubulin-binding antitumor agent with antimitotic, apoptosis-inducing, and vasculature disrupting activities.
原文英語
頁(從 - 到)182-191
頁數10
期刊Cancer Science
102
發行號1
DOIs
出版狀態已發佈 - 一月 2011

指紋

Antimitotic Agents
Antineoplastic Agents
Neoplasms
Tubulin
Nude Mice
Microtubules
Leukemia
N-(3-methyl-5-isothiazolyl)-2-1-((3-methyl-5-isoxazolyl)methyl)-1H-3-indolyl-2-oxoacetamide
Caco-2 Cells
G2 Phase
Colchicine
Growth
Cell Cycle Checkpoints
Human Activities
Polymerization
Uterine Cervical Neoplasms
Cell Division
Cisplatin
Biological Availability
Inhibitory Concentration 50

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

引用此文

Hu, C. B., Chen, C. P., Yeh, T. K., Song, J. S., Chang, C. Y., Chuu, J. J., ... Chen, C. T. (2011). BPR0C261 is a novel orally active antitumor agent with antimitotic and anti-angiogenic activities. Cancer Science, 102(1), 182-191. https://doi.org/10.1111/j.1349-7006.2010.01744.x

BPR0C261 is a novel orally active antitumor agent with antimitotic and anti-angiogenic activities. / Hu, Chih Bo; Chen, Ching Ping; Yeh, Teng Kuang; Song, Jen Shin; Chang, Chi Yen; Chuu, Jiunn Jye; Tung, Fei Feng; Ho, Pei Yin; Chen, Tung Wei; Lin, Chi Hung; Wang, Min Hsien; Chang, Kai Yen; Huang, Chen Lung; Lin, Heng Liang; Li, Wen Tai; Hwang, Der Ren; Chern, Jyh Haur; Hwang, Ling Ling; Chang, Jang Yang; Chao, Yu Sheng; Chen, Chiung Tong.

於: Cancer Science, 卷 102, 編號 1, 01.2011, p. 182-191.

研究成果: 雜誌貢獻文章

Hu, CB, Chen, CP, Yeh, TK, Song, JS, Chang, CY, Chuu, JJ, Tung, FF, Ho, PY, Chen, TW, Lin, CH, Wang, MH, Chang, KY, Huang, CL, Lin, HL, Li, WT, Hwang, DR, Chern, JH, Hwang, LL, Chang, JY, Chao, YS & Chen, CT 2011, 'BPR0C261 is a novel orally active antitumor agent with antimitotic and anti-angiogenic activities', Cancer Science, 卷 102, 編號 1, 頁 182-191. https://doi.org/10.1111/j.1349-7006.2010.01744.x
Hu, Chih Bo ; Chen, Ching Ping ; Yeh, Teng Kuang ; Song, Jen Shin ; Chang, Chi Yen ; Chuu, Jiunn Jye ; Tung, Fei Feng ; Ho, Pei Yin ; Chen, Tung Wei ; Lin, Chi Hung ; Wang, Min Hsien ; Chang, Kai Yen ; Huang, Chen Lung ; Lin, Heng Liang ; Li, Wen Tai ; Hwang, Der Ren ; Chern, Jyh Haur ; Hwang, Ling Ling ; Chang, Jang Yang ; Chao, Yu Sheng ; Chen, Chiung Tong. / BPR0C261 is a novel orally active antitumor agent with antimitotic and anti-angiogenic activities. 於: Cancer Science. 2011 ; 卷 102, 編號 1. 頁 182-191.
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AU - Chao, Yu Sheng

AU - Chen, Chiung Tong

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