The Dietary Flavonoid Fisetin Causes Cell Cycle Arrest, Caspase-Dependent Apoptosis, and Enhanced Cytotoxicity of Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells.

Fisetin (3,3',4',7-tetrahydroxyflavone), a flavonoid found in a number of fruits and vegetables, has diverse biological activities, including cytotoxic effects on cancer cells. In this study, we investigated the effect of fisetin on triple-negative breast cancer (TNBC) cells. TNBC has a poorer prognosis than other types of breast cancer and treatment options for this disease are limited. Fisetin inhibited the growth of MDA-MB-468 and MDA-MB-231 TNBC cells, as well as their ability to form colonies, without substantially affecting the growth of non-malignant cells. In addition, fisetin inhibited the growth of estrogen receptor-bearing MCF-7 breast cancer cells and human epidermal growth factor receptor 2-overexpressing SK-BR-3 breast cancer cells. Fisetin inhibited TNBC cell division and induced apoptosis, which was associated with mitochondrial membrane permeabilization and the activation of caspase-9 and caspase-8, as well as the cleavage of poly(ADP-ribose) polymerase-1. Induction of caspase-dependent apoptosis by fisetin was confirmed by reduced killing of TNBC cells in the presence of the pan-caspase inhibitors Z-VAD-FMK and BOC-D-FMK. Decreased phosphorylation of histone H3 at serine 10 in fisetin-treated TNBC cells at G2/M phase of the cell cycle suggested that fisetin-induced apoptosis was the result of Aurora B kinase inhibition. Interestingly, the cytotoxic effect of cisplatin, 5-fluorouracil, and 4-hydroxycyclophosphamide metabolite of cyclophosphamide on TNBC cells was increased in the presence of fisetin. These findings suggest that further investigation of fisetin is warranted for possible use in the management of TNBC. J. Cell. Biochem. 117: 1913-1925, 2016. © 2016 Wiley Periodicals, Inc.

10-Gingerol Inhibits Ovarian Cancer Cell Growth by Inducing G2 Arrest.

Purpose: Gingerol homologs found in the rhizomes of ginger plants have the potential to benefit human health, including the prevention and treatment of cancer. This study evaluated the effect of 10-gingerol on ovarian cancer cell (HEY, OVCAR3, and SKOV-3) growth. Methods: Cell growth was measured by MTT assays, flow cytometry was used to assess cell proliferation, cytotoxicity and cell cycle progression, and western blotting was used to measure cyclin protein expression. Results: Ovarian cancer cells that were treated with 10-gingerol experienced a time- and dose-dependent decrease in cell number, which was due to a reduction in cell proliferation rather than a cytotoxic effect. Reduced proliferation of 10-gingerol-treated ovarian cancer cells was associated with an increased percentage of cells in G2 phase of the cell cycle and a corresponding reduction in the percentage of cells in G1. Ovarian cancer cells also showed decreased cyclin A, B1, and D3 expression following exposure to 10-gingerol. Conclusion: These findings revealed that 10-gingerol caused a G2 arrest-associated suppression of ovarian cancer cell growth, which may be exploited in the management of ovarian cancer.