Oncotarget

Research Papers:

The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo

Masashi Okada, Kenta Kuramoto, Hiroyuki Takeda, Hikaru Watarai, Hirotsugu Sakaki, Shizuka Seino, Manabu Seino, Shuhei Suzuki and Chifumi Kitanaka _

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Oncotarget. 2016; 7:27021-27032. https://doi.org/10.18632/oncotarget.8395

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Abstract

Masashi Okada1, Kenta Kuramoto1, Hiroyuki Takeda1,2, Hikaru Watarai1,3, Hirotsugu Sakaki1,4, Shizuka Seino1,5, Manabu Seino1,4, Shuhei Suzuki1,2 and Chifumi Kitanaka1,5

1 Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan

2 Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan

3 Second Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan

4 Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan

5 Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata , Japan

Correspondence to:

Chifumi Kitanaka, email:

Keywords: cancer initiating cells, c-Jun N-terminal kinase, drug repositioning, serial transplantation assay, xenograft

Received: August 27, 2015 Accepted: March 16, 2016 Published: March 26, 2016

Abstract

A phase 2 clinical trial investigating the efficacy and safety of AS602801, a newly developed JNK inhibitor, in the treatment of inflammatory endometriosis is complete. We are now examining whether AS602801 acts against human cancer cells in vitro and in vivo. In vitro, AS602801 exhibited cytotoxicity against both serum-cultured non-stem cancer cells and cancer stem cells derived from human pancreatic cancer, non-small cell lung cancer, ovarian cancer and glioblastoma at concentrations that did not decrease the viability of normal human fibroblasts. AS602801 also inhibited the self-renewal and tumor-initiating capacity of cancer stem cells surviving AS602801 treatment. Cancer stem cells in established xenograft tumors were reduced by systemic administration of AS602801 at a dose and schedule that did not adversely affect the health of the tumor-bearing mice. These findings suggest AS602801 is a promising anti-cancer stem cell agent, and further investigation of the utility of AS602801 in the treatment of cancer seems warranted.


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