[10]-Gingerol, a major phenolic constituent of ginger root, induces cell cycle arrest and apoptosis in triple-negative breast cancer cells.
The ginger rhizome is rich in bioactive compounds, including [6]-gingerol, [8]-gingerol, and [10]-gingerol; however, to date, most research on the anti-cancer activities of gingerols have focused on [6]-gingerol. In this study, we compared [10]-gingerol with [8]-gingerol and [6]-gingerol in terms of their ability to inhibit the growth of human and mouse mammary carcinoma cells. A colorimetric assay based on the enzymatic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide revealed that [10]-gingerol was more potent than [6]-gingerol and at least as potent as [8]-gingerol for the inhibition of triple-negative human (MDA-MB-231, MDA-MB-468) and mouse (4T1, E0771) mammary carcinoma cell growth. Further investigation of [10]-gingerol showed that it suppressed the growth of estrogen receptor-bearing (MCF-7, T47D) and HER2-overexpressing (SKBR3) breast cancer cells. The inhibitory effect of [10]-gingerol on the growth of MDA-MB-231 cells was associated with a reduction in the number of rounds of cell division and evidence of S phase-cell cycle arrest, as well as induction of apoptosis due to mitochondrial outer membrane permeabilization and the release of proapoptotic mitochondrial cytochrome c and SMAC/DIABLO into the cytoplasm. Surprisingly, killing of MDA-MB-231 cells by [10]-gingerol was not affected by a pan-caspase inhibitor (zVAD-fmk) or an anti-oxidant (N-acetylcysteine), suggesting that the cytotoxic effect of [10]-gingerol did not require caspase activation or the accumulation of reactive oxygen species. These findings suggest that further investigation of [10]-gingerol is warranted for its possible use in the treatment of breast cancer.
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
Megan M
MM
Bernard
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
Jason R
JR
McConnery
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada; Department of Surgery, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada. Electronic address: d.w.hoskin@dal.ca.
David W
DW
Hoskin
D000111:Acetylcysteine / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005233:Fatty Alcohols / Q000494:pharmacology*; D005260:Female; D020939:Zingiber officinale / Q000737:chemistry*; D006801:Humans; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*
D000590:Amino Acid Chloromethyl Ketones; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D002396:Catechols; C499605:Diablo protein, mouse; D005233:Fatty Alcohols; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C007845:gingerol; C505409:Casp3 protein, mouse; D053148:Caspase 3; D000111:Acetylcysteine
Apoptosis; Breast cancer; Cell cycle; Gingerol