Breast cancer is one of the common tumors occurring in woman and despite treatment, the prognostic is poor. Genistein, a soy isoflavone, has been reported to have chemopreventive\chemotherapeutic potential in multiple tumor types. Here, we investigated the genistein antiproliferative effect in MCF-7 breast cancer, underlying the molecular mechanisms involved in this effect. MCF-7 cancer and CCD1059sK fibroblast cells were treated with estradiol (10 nM) or genistein (0.01-100 μM) for 24, 48, and 72 h and the cell proliferation was investigated by MTT; membrane cell permeability was evaluated by LDH and PI incorporation; apoptosis was investigated by externalization of phosphatidylserine by FACS; and presence of autophagy was detected by LC3A/B immunostaining. The expression of apoptotic proteins and antioxidant enzymes was evaluated by qPCR. The results demonstrate that genistein (100 μM) for 72 h of treatment selectively reduced MCF-7 cell proliferation independent of estrogen receptor activation, while no cytotoxicity was observed in fibroblast cells. Further experiments showed that genistein induced phosphatidylserine externalization and LC3A/B immunopositivity in MCF-7 cells, indicating apoptosis and autophagy cell death. Genistein increased in three times proapoptotic BAX/Bcl-2 ratio and promoted a parallel downregulation of 20 times of antiapoptotic survivin. In addition, genistein promoted a decrease of 5.5, 9.3, and 3.6 times of MnSOD, CuZnSOD, and TrxR mRNA expression, respectively, while the GPx expression was increased by 6.5 times. These results suggest that the antitumor effect of genistein involved the modulation of antioxidant enzyme and apoptotic signaling expression, which resulted in apoptosis and progression of autophagy.
Rosmarinic acid is commonly found in species of the Boraginaceae and the subfamily Nepetoideae (Lamiaceae). It has a number of interesting biological activities, for example, antiviral, antibacterial, anti-inflammatory, and antioxidant. The aim of the present study was to investigate the effect of the i.p. administration of caffeic and rosmarinic acid (5 and 10 mg/kg) on anti-inflammatory and nociceptive response using carrageenan-induced pleurisy model and tail-flick assay in rats. The analysis of cells in the pleural exudates revealed a reduction of 66% of the number of leukocytes that migrated to the pleural cavity in the animals treated with 5 mg/kg caffeic acid, and of 92.9% for the animals treated with 10 mg/kg in comparison with the control group. These exudates showed a balanced distribution of polymorphonuclear (PMN) and mononuclear (MN) cells, differently from the control group, in which PMN cells were predominant. The analysis to tail-flick latency was increased in the group treated with 10 mg/kg caffeic acid characterizing a nociceptive response. While there was no difference between control group and animals treated with rosmarinic.
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