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

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)182-191
Number of pages10
JournalCancer Science
Issue number1
Publication statusPublished - Jan 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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