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

• Published in: International journal of molecular sciences 2021-04, Vol.22 (9), p.4660
• Main Authors: Sp, Nipin, Kang, Dong Young, Lee, Jin-Moo, Bae, Se Won, Jang, Kyoung-Jin
• Format: Article
• Language: English
• Subjects: 6-Gingerol; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor activity; Apoptosis; Apoptosis - drug effects; Ataxia; BAX protein; Bcl-2 protein; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Catechols - pharmacology; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell division; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclin-dependent kinases; Cytochrome c; DDR; Deoxyribonucleic acid; DNA; DNA Damage; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - metabolism; Fatty Alcohols - pharmacology; Female; G0/G1 arrest; Ginger; Gingerol; Growth factors; Humans; Kinases; MCF-7 Cells; Microscopy; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; mitochondrial apoptosis; Models, Biological; Morphology; p53; p53 Protein; Phosphorylation; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Side effects; Signal transduction; Signal Transduction - drug effects; Spheroids, Cellular - drug effects; Spheroids, Cellular - pathology; src-Family Kinases - metabolism; Stat3 protein; STAT3 Transcription Factor - metabolism; Tumor cell lines; Tumor Suppressor Protein p53 - metabolism; Tumorigenesis; tumorsphere; Zingiber officinale - chemistry
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22094660

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.