Anticancer activity of peach and plum extracts against human breast cancer in vitro and in vivo
Noratto Dongo, Giuliana Doris
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Commercial varieties of peaches and plums contain a mixture of phenolics that may possess anticancer activity. Our objectives were to evaluate extracts from a commercial variety of yellow fleshed peach "Rich Lady" (RL) and of the red fleshed plum "Black Splendor" (BS) on tumor breast cells in vitro and in vivo, to elucidate the molecular mechanisms behind the cancer growth-suppression of the phenolics identified in peach and plum extracts for their chemopreventive potential and to evaluate the tumor growth-suppression in vivo. The RL extract preferentially inhibited the proliferation of the estrogen-independent MDA-MB-435 breast cancer cells over the estrogen-dependent MCF-7 or the normal MCF-10A breast cells. Similarly, BS extracts, though less effective than RL extracts, showed greater effects on MDA-MB-435 cells compared to the other cell lines. Fractionation of RL extracts into different groups of phenolic compounds allowed the identification of a fraction of phenolic acids (F1) with the major components of chlorogenic and neo-chlorogenic acid with potential in chemoprevention because of the relatively high growth-inhibition exerted on MDA-MB-435 and low toxicity exerted on MCF-10A cells. The F1 isolated from RL, and its major components, chlorogenic and neo-chlorogenic acids, triggered the extrinsic and intrinsic apoptotic pathways. The extrinsic death-receptor pathway involved the activation of caspase-8 followed by caspase-6, caspase-7, and PARP cleavage. By targeting the intrinsic pathway, the pro-apoptotic proteins cytochrome c, EndoG and AIF were released from mitochondria. The relatively higher cell-growth inhibition exerted by neo-chlorogenic acid was associated with its ability to inhibit the pro-survival Akt pathway. In contrast, F1 isolated from the red flesh genotype BY00P6653, induced apoptosis mainly through the intrinsic mitochondrial pathway upon sustained MAPK-ERK1/2 phosphorylation. The tumor growth-suppression of RL extracts was confirmed in vivo. Moreover, a dose-dependent decrease in lung metastasis was found, even at doses that showed no effect in tumor growth-suppression. These results suggest that peach phenolics may have potential in therapy and chemoprevention of metastatic breast cancer. Specifically chlorogenic and neo-chlorogenic acids, widely distributed among food plants, may be a useful therapeutic tool for targeting multiple cell signaling pathways in the treatment and chemoprevention of metastatic breast cancer.