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Article

Potential Antitumor Effects of 6-Gingerol in p53-Dependent Mitochondrial Apoptosis and Inhibition of Tumor Sphere Formation in Breast Cancer Cells

1
Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Chungju 27478, Korea
2
Pharmacological Research Division, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex, Cheongju 28159, Korea
3
Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Academic Editor: Antonella Zannetti
Int. J. Mol. Sci. 2021, 22(9), 4660; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094660
Received: 30 March 2021 / Revised: 26 April 2021 / Accepted: 27 April 2021 / Published: 28 April 2021
(This article belongs to the Special Issue Breast Cancer: From Pathophysiology to Novel Therapeutic Approaches)
Hormone-specific anticancer drugs for breast cancer treatment can cause serious side effects. Thus, treatment with natural compounds has been considered a better approach as this minimizes side effects and has multiple targets. 6-Gingerol is an active polyphenol in ginger with various modalities, including anticancer activity, although its mechanism of action remains unknown. Increases in the level of reactive oxygen species (ROS) can lead to DNA damage and the induction of DNA damage response (DDR) mechanism, leading to cell cycle arrest apoptosis and tumorsphere suppression. Epidermal growth factor receptor (EGFR) promotes tumor growth by stimulating signaling of downstream targets that in turn activates tumor protein 53 (p53) to promote apoptosis. Here we assessed the effect of 6-gingerol treatment on MDA-MB-231 and MCF-7 breast cancer cell lines. 6-Gingerol induced cellular and mitochondrial ROS that elevated DDR through ataxia-telangiectasia mutated and p53 activation. 6-Gingerol also induced G0/G1 cell cycle arrest and mitochondrial apoptosis by mediating the BAX/BCL-2 ratio and release of cytochrome c. It also exhibited a suppression ability of tumorsphere formation in breast cancer cells. EGFR/Src/STAT3 signaling was also determined to be responsible for p53 activation and that 6-gingerol induced p53-dependent intrinsic apoptosis in breast cancer cells. Therefore, 6-gingerol may be used as a candidate drug against hormone-dependent breast cancer cells. View Full-Text
Keywords: 6-Gingerol; DDR; G0/G1 arrest; mitochondrial apoptosis; tumorsphere; p53; EGFR/Src/STAT3 6-Gingerol; DDR; G0/G1 arrest; mitochondrial apoptosis; tumorsphere; p53; EGFR/Src/STAT3
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MDPI and ACS Style

Sp, N.; Kang, D.Y.; Lee, J.-M.; Bae, S.W.; Jang, K.-J. Potential Antitumor Effects of 6-Gingerol in p53-Dependent Mitochondrial Apoptosis and Inhibition of Tumor Sphere Formation in Breast Cancer Cells. Int. J. Mol. Sci. 2021, 22, 4660. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094660

AMA Style

Sp N, Kang DY, Lee J-M, Bae SW, Jang K-J. Potential Antitumor Effects of 6-Gingerol in p53-Dependent Mitochondrial Apoptosis and Inhibition of Tumor Sphere Formation in Breast Cancer Cells. International Journal of Molecular Sciences. 2021; 22(9):4660. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094660

Chicago/Turabian Style

Sp, Nipin, Dong Y. Kang, Jin-Moo Lee, Se W. Bae, and Kyoung-Jin Jang. 2021. "Potential Antitumor Effects of 6-Gingerol in p53-Dependent Mitochondrial Apoptosis and Inhibition of Tumor Sphere Formation in Breast Cancer Cells" International Journal of Molecular Sciences 22, no. 9: 4660. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094660

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