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An analogue of resveratrol HS-1793 exhibits anticancer activity against MCF-7 cells via inhibition of mitochondrial biogenesis gene expression
- Source :
- Molecules and Cells. 34:357-365
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
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.
- Subjects :
- Programmed cell death
Cell Survival
Mitochondrial Turnover
Down-Regulation
Antineoplastic Agents
Naphthols
Resveratrol
Oxidative Phosphorylation
Mitochondrial Proteins
chemistry.chemical_compound
Stilbenes
Humans
Molecular Biology
Caspase
Membrane Potential, Mitochondrial
biology
food and beverages
Resorcinols
Articles
Cell Biology
General Medicine
TFAM
Cell biology
Gene Expression Regulation, Neoplastic
MCF-7
Mitochondrial biogenesis
Biochemistry
chemistry
Caspases
Cancer cell
MCF-7 Cells
biology.protein
Drug Screening Assays, Antitumor
Subjects
Details
- ISSN :
- 02191032 and 10168478
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Molecules and Cells
- Accession number :
- edsair.doi.dedup.....db362fa2f60224b97ac605aef8061ba3