Abstract
DNA targeting anticancer agents have been very successful in clinic, especially, when used in combinatorial therapy. But unfortunately, they often exhibit high levels of toxicity towards normal cells. Hence, much effort has been put into finding agents with more selectivity, and less toxicity. Pectins are natural polysaccharides, and beneficial nutritional fibers that have attracted attentions due to their antitumor properties. However, their molecular targets, and mechanism of action are widely unknown. Here, we have reported that citrus pectin (CP) and apple pectin (AP) selectively suppress viability in MDA-MB-231, MCF-7 and T47D human Breast cancer cells, while non-toxic to L929 normal cells. Upon CP, and AP treatments, cancer cells’ ROS content increased rapidly, and led to the collapse of the mitochondrial transmembrane potential which functions upstream of the caspase-dependent apoptosis. CP and AP treated cancer cells were also arrested at the S and G1 or G2/M phases of the cell cycle, respectively. Furthermore, mRNA expression of Galectin-3 (a multi-functional lectin involved in cell adhesion, cell cycle, and apoptosis) reduced in both CP and AP treated cells. Growth inhibition of MDA-MB-231 cells by CP, and AP was concomitant with DNA damage (oxidation, and strand breaks). In this context, in an effort to clarify the mechanism of action, we showed that CP, and AP are able to interact with DNA. The strength and mode of DNA binding were established by spectroscopy techniques. We demonstrated that CP, and AP bind to dsDNA by intercalation, and groove binding/partial intercalation, respectively. In conclusion, our findings suggest that CP, and AP induce apoptosis in MDA-MB-231 cells by increasing the release of ROS, which may be related to the mitochondrial apoptosis pathway, and direct interactions with DNA. Our data indicate that these compounds may be potentially useful in cancer treatment.
Highlights
According to the World Health Organization (WHO), Breast cancer with about half a million death, and nearly 1.7 million new cases annually accounts for 25.2% of cancer cases, and is the most common malignancy among women
Growth inhibition induced by Citrus Pectin (CP), and Apple Pectin (AP) after 48, and 72 h treatments in three human Breast cancer cell lines including MDA-MB-231 (ER−/PR−/HER-2-), MCF-7, and T47D (ER+/PR+, HER-2-), and non-tumorigenic fibroblast L929 cells was evaluated
The comet assay analysis results are presented in Box and whiskers plots (Fig. 5C). These results indicate that the apoptosis induced by CP, and AP is tightly correlated with DNA damage
Summary
According to the World Health Organization (WHO), Breast cancer with about half a million death, and nearly 1.7 million new cases annually accounts for 25.2% of cancer cases, and is the most common malignancy among women. Pectins are capable of inducing apoptosis in cancer cells without having any adverse effect on normal cells, which make them good candidates in drug research. Previous studies, both in vitro and in vivo, demonstrated that modified pectins by high pH, and temperature possess chemo preventive properties against cancer cells in Breast, colon, prostate, melanoma, and multiple myeloma cancers. Apple Pectin (AP) or Citrus Pectin (CP) cannot completely prevent metastatic tumor formation, but, recent findings indicate that CP, AP, and pectic polymer are able to induce apoptosis in various cancer cells via inhibiting MAP kinase activation, and NF-kB inactivation[23]
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