Tart cherry juice induces differential dose-dependent effects on apoptosis, but not cellular proliferation, in MCF-7 human breast cancer cells.
Consumption of polyphenol-rich fruits, for example, tart cherries, is associated with a lower risk of cardiovascular disease and cancer. This is due, in large part, to the diverse myriad bioactive agents, that is, polyphenol anthocyanins, present in fruits. Anthocyanin-rich tart cherries purportedly modulate numerous cellular processes associated with oncogenesis such as apoptosis, cellular proliferation (CP), and cell cycle progression, although the effective concentrations eliciting these effects are unclear. We hypothesized that several dose-dependent effects over a large concentration range of 100% tart cherry juice (TCJ) would exist and affect these processes differentially with the potential for cellular protection and cellular death either by apoptosis or by necrosis. In this in vitro study, we tested the dose response of TCJ on CP and cell death in MCF-7 human breast cancer cells. TCJ was added at 0.03-30% (v/v) to cells and incubated overnight with the medium alone or with increasing TCJ. Bromodeoxyuridine incorporation was significantly reduced by 20% at ≥10% (v/v) TCJ and associated with necrosis, but was not different between the control and treatment groups at <10% TCJ. MTT reduction was also significantly reduced by 27% and 80% at 10% and 30% TCJ, respectively, and associated with necrosis. Apoptosis, but not necrosis, was increased ∼63% at 3% TCJ (∼307 nM monomeric anthocyanins), yet significantly decreased (P<.05) by 20% at 1% TCJ (920 nM) both of which were physiologically relevant concentrations of anthocyanins. The data support a biphasic effect on apoptosis and no effect on proliferation.
Healthy Lifestyles Research Center, Arizona State University, Mesa, Arizona 85212, USA. keith.r.martin@asu.edu
Keith R
KR
Martin
Alissa
A
Wooden
D000872:Anthocyanins / Q000032:analysis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001628:Beverages / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D061986:MCF-7 Cells; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis / Q000188:drug therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols / Q000032:analysis / Q000494:pharmacology; D027861:Prunus / Q000737:chemistry*
D000872:Anthocyanins; D010936:Plant Extracts; D059808:Polyphenols; D007770:L-Lactate Dehydrogenase; D001973:Bromodeoxyuridine