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Mol. Cells 2012; 34(4): 357-365

Published online October 31, 2012

https://doi.org/10.1007/s10059-012-0081-7

© The Korean Society for Molecular and Cellular Biology

An Analogue of Resveratrol HS-1793 Exhibits Anticancer Activity Against MCF-7 Cells Via Inhibition of Mitochondrial Biogenesis Gene Expression

Seung Hun Jeong, In Sung Song, Hyoung Kyu Kim, Sung Ryul Lee, Suhee Song1, Hongsuk Suh1, Young Geol Yoon2, Young Hyun Yoo3, Nari Kim, Byoung Doo Rhee, Kyung Soo Ko, and Jin Han*

National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea, 1Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 609-735, Korea, 2Department of Biomedical Science, Institute for Biomedical and Health Sciences, Jungwon University, Goesan 367-700, Korea, 3Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan 602-714, Korea

Correspondence to : *Correspondence: phyhanj@inje.ac.kr

Received: March 19, 2012; Revised: July 24, 2012; Accepted: September 7, 2012

Abstract

Resveratrol is a phytoalexin and polyphenol derived from grapes, berries, and peanuts. It has been shown to medi-ate death of a wide variety of cancer cells. Although resveratrol is considered an important potential chemo-therapeutic 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.

Keywords HS-1793, mitochondrial biological function, oxygen consumption rate, resveratrol, TFAM

Article

Research Article

Mol. Cells 2012; 34(4): 357-365

Published online October 31, 2012 https://doi.org/10.1007/s10059-012-0081-7

Copyright © The Korean Society for Molecular and Cellular Biology.

An Analogue of Resveratrol HS-1793 Exhibits Anticancer Activity Against MCF-7 Cells Via Inhibition of Mitochondrial Biogenesis Gene Expression

Seung Hun Jeong, In Sung Song, Hyoung Kyu Kim, Sung Ryul Lee, Suhee Song1, Hongsuk Suh1, Young Geol Yoon2, Young Hyun Yoo3, Nari Kim, Byoung Doo Rhee, Kyung Soo Ko, and Jin Han*

National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea, 1Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 609-735, Korea, 2Department of Biomedical Science, Institute for Biomedical and Health Sciences, Jungwon University, Goesan 367-700, Korea, 3Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan 602-714, Korea

Correspondence to:*Correspondence: phyhanj@inje.ac.kr

Received: March 19, 2012; Revised: July 24, 2012; Accepted: September 7, 2012

Abstract

Resveratrol is a phytoalexin and polyphenol derived from grapes, berries, and peanuts. It has been shown to medi-ate death of a wide variety of cancer cells. Although resveratrol is considered an important potential chemo-therapeutic 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.

Keywords: HS-1793, mitochondrial biological function, oxygen consumption rate, resveratrol, TFAM

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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