title: The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo.
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.
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kuramoto
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Second Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Watarai
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Sakaki
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata , Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Seino
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Seino
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata , Japan.
authors.forename: Chifumi
authors.initials: C
authors.lastname: Kitanaka
mesh_terms: D000072283:A549 Cells; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D052160:Benzothiazoles; D011743:Pyrimidines; D048031:JNK Mitogen-Activated Protein Kinases; C000609147:bentamapimod
keywords: c-Jun N-terminal kinase; cancer initiating cells; drug repositioning; serial transplantation assay; xenograft