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Surface modified PAMAM dendrimers with gallic acid inhibit, cell proliferation, cell migration and inflammatory response to augment apoptotic cell death in human colon carcinoma cells.

To overcome the obstacle of anti-cancer therapy significant attention has been drawn for improving drug delivery system. Since recent past, different approaches were applied using synthetic or natural derivatives for improving efficacy of anti-cancer drugs in cancer therapeutics. Gallic acid (GA) is a natural polyphenol, which exhibits a broad spectrum of biological activities, but its therapeutic application was limited due to poor bioavailability and toxicity. In the present study, we had conjugated the GA with PAMAM dendrimers and proposed the insights of molecular mechanism on inhibition of cell proliferation and programmed cell death through apoptotic pathway in human colon carcinoma cells. GA was chemically conjugated with 4.0 G PAMAM dendrimer at outer surface and characterized by different biophysical methods. We further examined its bioavailability, anti-cancer activity and explored the molecular mechanism of programmed cell death signaling in HCT116 cells. The results show that PAMAM-GA conjugate inhibits cell proliferation of different origin of cancer cells, improves cellular uptake of GA, inhibits colonogenic ability, restricts cancer cell migration by down regulating the expression of MMP-9, inhibits NF-kB activation and release of pro-inflammatory cytokines to manifest apoptotic cell death in HCT 116 cells rather than necrosis. On other hand, PAMAM-GA conjugate showed negligible cytotoxic response as compared to the free Gallic acid to the normal cells. In conclusion, findings of this study revealed that PAMAM-GA conjugate improves the bioavailability of GA and specificity towards cancer cellsto manifests apoptotic cell death. This indispensable approach may be beneficial for the revolution of anti-cancer therapy. Communicated by Ramaswamy H. Sarma.

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