Synthesis of apoptotic chalcone analogues in HepG2 human hepatocellular carcinoma cells

Cheon-Soo Park; Yongchel Ahn; Dahae Lee; Sung Won Moon; Ki Hyun Kim; Noriko Yamabe; Gwi Seo Hwang; Hyuk Jai Jang; Heesu Lee; Ki Sung Kang; Jae Wook Lee

doi:10.1016/j.bmcl.2015.10.093

Synthesis of apoptotic chalcone analogues in HepG2 human hepatocellular carcinoma cells

Bioorg Med Chem Lett. 2015 Dec 15;25(24):5705-7. doi: 10.1016/j.bmcl.2015.10.093. Epub 2015 Oct 31.

Authors

Cheon-Soo Park¹, Yongchel Ahn², Dahae Lee³, Sung Won Moon⁴, Ki Hyun Kim⁵, Noriko Yamabe³, Gwi Seo Hwang³, Hyuk Jai Jang¹, Heesu Lee⁶, Ki Sung Kang⁷, Jae Wook Lee⁸

Affiliations

¹ Department of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung 210-711, Republic of Korea.
² Department of Hematology and Oncology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung 210-711, Republic of Korea.
³ College of Korean Medicine, Gachon University, Seongnam 461-701, Republic of Korea.
⁴ Department of Chemistry, Gangneung Wonju National University, Gangneung 210-340, Republic of Korea; Natural Product Research Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea.
⁵ Natural Product Research Laboratory, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
⁶ Department of Oral Anatomy, College of Dentistry, Gangneung Wonju National University, 201-340, Republic of Korea.
⁷ College of Korean Medicine, Gachon University, Seongnam 461-701, Republic of Korea. Electronic address: kkang@gachon.ac.kr.
⁸ Natural Product Research Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea; Department of Biological Chemistry, University of Science and Technology (UST), Daejeon 305-333, Republic of Korea. Electronic address: jwlee5@kist.re.kr.

PMID: 26564263
DOI: 10.1016/j.bmcl.2015.10.093

Abstract

Eight chalcone analogues were prepared and evaluated for their cytotoxic effects in human hepatoma HepG2 cells. Compound 5 had a potent cytotoxic effect. The percentage of apoptotic cells was significantly higher in compound 5-treated cells than in control cells. Exposure to compound 5 for 24h induced cleavage of caspase-8 and -3, and poly (ADP-ribose) polymerase (PARP). Our findings suggest that compound 5 is the active chalcone analogue that contributes to cell death in HepG2 cells via the extrinsic apoptotic pathway.

Keywords: Anticancer; Apoptosis; Chalcone; HepG2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Caspase 3 / metabolism
Caspase 8 / metabolism
Cell Survival / drug effects
Chalcone / chemical synthesis
Chalcone / chemistry*
Chalcone / pharmacology
Hep G2 Cells
Humans
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Poly(ADP-ribose) Polymerases / metabolism

Substances

Antineoplastic Agents
Chalcone
Poly(ADP-ribose) Polymerases
Caspase 3
Caspase 8