Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines.
Bottom Line: Lycopene treatment for 168 consecutive hours exhibited a time-dependent and dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0 /G1 phase at physiologically achievable concentrations found in human plasma.The greatest growth inhibition was observed in MDA-MB-468 where the sub-G0 /G1 apoptotic population was significantly increased, with demonstrable cleavage of PARP.In triple negative cells, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax without affecting anti-apoptotic Bcl-xL.
Affiliation: Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Fukuoka, Japan.Show MeSH
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Mentions: Cleavage of PARP was demonstrated from 24 to 72 h after initiation of the treatment in all three cell lines treated with lycopene (Fig.3b). The densities of western blot for PARP cleavage in MCF-7 and SK-BR-3 cells appeared less than those of MDA-MB-468 cells, supporting lower incidence of lycopene-induced apoptosis in MCF-7 and SK-BR-3 cells. Because activations of signaling molecules such as ERK1/2, Akt and mTOR have been considered as major factors contributing toward proliferation and survival, we examined the effects of lycopene on expression or activation (phosphorylation) of these proteins in these three breast cancer cell lines. Upon treatment with lycopene, the constitutive activity of ERK1/2 was enhanced 6 h after initiation of treatment in these three cell lines, and remained at high levels over 24 h (Fig.3a). By contrast, the phosphorylation of Akt and its downstream molecule mTOR was only inhibited time-dependently in MDA-MB-468 cells but not in MCF-7 and SK-BR-3 cells (Fig.3a). Cyclin D1 functioning as a key regulator of G0/G1 cell cycle checkpoint was inhibited with subsequent increase of p21 protein in all cell lines, indicating that lycopene arrests the cell cycle at G0/G1 through decrease in cyclin D1 expression and concomitant upregulation of p21 regardless of the subtypes of breast cancer.
Affiliation: Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Fukuoka, Japan.