Antitumor effects of flavopiridol, a cyclin-dependent kinase inhibitor, on human cholangiocarcinoma in vitro and in an in vivo xenograft model

Saowaluk Saisomboon; Ryusho Kariya; Kulthida Vaeteewoottacharn; Sopit Wongkham; Kanlayanee Sawanyawisuth; Seiji Okada

doi:10.1016/j.heliyon.2019.e01675

Antitumor effects of flavopiridol, a cyclin-dependent kinase inhibitor, on human cholangiocarcinoma in vitro and in an in vivo xenograft model

Heliyon. 2019 May 9;5(5):e01675. doi: 10.1016/j.heliyon.2019.e01675. eCollection 2019 May.

Authors

Saowaluk Saisomboon^{1

2

3}, Ryusho Kariya³, Kulthida Vaeteewoottacharn^{1

2}, Sopit Wongkham^{1

2}, Kanlayanee Sawanyawisuth^{1

2}, Seiji Okada³

Affiliations

¹ Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
² Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand.
³ Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.

Abstract

Flavopiridol, a pan-cyclin-dependent kinase (CDK) inhibitor, was recently identified as an effective antitumor agent for several cancers. We investigated the antitumor effect of flavopiridol on cholangiocarcinoma (CCA), in vitro and in vivo. A methylthiotetrazole assay revealed that the proliferation of certain CCA cells was inhibited by flavopiridol, which induced the caspase-dependent apoptosis of CCA cells. Although increased cell cycle arrest was observed at the G2/M phase, caspase activation occurred earlier than 24 h, indicating that caspase-dependent apoptosis is the major pathway for the suppression of cell proliferation. Flavopiridol potently reduced the CCA tumor growth in a xenograft model without observable adverse effects. These findings indicated that flavopiridol could be a potential antitumor agent for the treatment of CCA.

Keywords: Biochemistry; Cancer research; Molecular biology.