title: An analogue of resveratrol HS-1793 exhibits anticancer activity against MCF-7 cells via inhibition of mitochondrial biogenesis gene expression.
abstract: Resveratrol is a phytoalexin and polyphenol derived from grapes, berries, and peanuts. It has been shown to mediate death of a wide variety of cancer cells. Although resveratrol is considered an important potential chemotherapeutic agent, it is required at high doses to achieve a biologically or physiologically significant effect, which may be impractical for treating cancer. Thus, a more stable and potent derivative of resveratrol, with more effective tumoricidal activity, must be developed. A novel resveratrol analog, HS-1793, has recently been synthesized and was determined to exhibit a greater decrease in cancer cell viability than resveratrol. However, the underlying mechanism of HS-1793-induced cancer cell death remains unknown. We thus investigated the mechanism by which HS-1793 induces cell death and assessed whether this occurs through a mitochondrial-mediated mechanism. Using the MCF-7 breast cancer cell line, we determined that HS-1793 treatment significantly increased cell death at a relatively low dose compared with resveratrol. HS-1793 treatment more significantly decreased mitochondrial membrane potential, cellular ATP concentration, and cellular oxygen consumption rate than resveratrol treatment. At the molecular level, HS-1793 treatment down-regulated the expression of major mitochondrial biogenesis-regulating proteins, including mitochondrial transcriptional factor A (TFAM), Tu translation elongation factor (TUFM), and single-stranded DNA-binding protein. We conclude that HS- 1793 acts by regulating the expression of TFAM and TUFM, leading to a block in normal mitochondrial function, which sensitizes cancer cells to cell death. We therefore propose that HS-1793 can be a useful chemosensitization agent, which together with other such agents can efficiently target cancer cells.
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, 614-735, Korea.
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Jeong
authors.forename: In Sung
authors.initials: IS
authors.lastname: Song
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Sung Ryul
authors.initials: SR
authors.lastname: Lee
authors.forename: Suhee
authors.initials: S
authors.lastname: Song
authors.forename: Hongsuk
authors.initials: H
authors.lastname: Suh
authors.forename: Young Geol
authors.initials: YG
authors.lastname: Yoon
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Byoung Doo
authors.initials: BD
authors.lastname: Rhee
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Ko
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D063269:Mitochondrial Turnover / Q000187:drug effects / Q000235:genetics*; D009284:Naphthols / Q000737:chemistry / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D012118:Resorcinols / Q000737:chemistry / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: C523393:4-(6-hydroxy-2-naphthyl)-1,3-benzenediol; D000970:Antineoplastic Agents; D024101:Mitochondrial Proteins; D009284:Naphthols; D012118:Resorcinols; D013267:Stilbenes; D020169:Caspases; D000077185:Resveratrol