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: Seung Hun Jeong, In Sung Song, Hyoung Kyu Kim, Sung Ryul Lee, Suhee Song, Hongsuk Suh, Young Geol Yoon, Young Hyun Yoo, Nari Kim, Byoung Doo Rhee, Kyung Soo Ko, Jin Han
• Journal: Molecules and cells (Mol Cells) Vol. 34 Issue 4 Pg. 357-65 (Oct 2012) ISSN: 0219-1032 [Electronic] Korea (South)
• PMID: 23104437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-(6-hydroxy-2-naphthyl)-1,3-benzenediol
• Antineoplastic Agents
• Mitochondrial Proteins
• Naphthols
• Resorcinols
• Stilbenes
• Caspases
• Resveratrol

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Caspases (metabolism)
• Cell Survival (drug effects, genetics)
• Down-Regulation (drug effects, genetics)
• Drug Screening Assays, Antitumor
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• MCF-7 Cells
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondrial Proteins (genetics, metabolism)
• Mitochondrial Turnover (drug effects, genetics)
• Naphthols (chemistry, pharmacology)
• Oxidative Phosphorylation (drug effects)
• Resorcinols (chemistry, pharmacology)
• Resveratrol
• Stilbenes (chemistry, metabolism)