Inhibition of angiogenesis- and inflammation-inducing factors in human colon cancer cells in vitro and in ovo by free and nanoparticle-encapsulated redox dye, DCPIP

Fadee G Mondalek,Shrikant Anant,Sivapriya Ponnurangam,Rama P Ramanujam,Courtney Houchen,Panayotis Pantazis,Janita Govind

doi:10.1186/1477-3155-8-17

Fadee G Mondalek, Shrikant Anant + Show 5 more

Open Access

https://doi.org/10.1186/1477-3155-8-17

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Abstract

BackgroundThe redox dye, DCPIP, has recently shown to exhibit anti-melanoma activity in vitro and in vivo. On the other hand, there is increasing evidence that synthetic nanoparticles can serve as highly efficient carriers of drugs and vaccines for treatment of various diseases. These nanoparticles have shown to serve as potent tools that can increase the bioavailability of the drug/vaccine by facilitating absorption or conferring sustained and improved release. Here, we describe results on the effects of free- and nanoparticle-enclosed DCPIP as anti-angiogenesis and anti-inflammation agents in a human colon cancer HCT116 cell line in vitro, and in induced angiogenesis in ovo.ResultsThe studies described in this report indicate that (a) DCPIP inhibits proliferation of HCT116 cells in vitro; (b) DCPIP can selectively downregulate expression of the pro-angiogenesis growth factor, VEGF; (c) DCPIP inhibits activation of the transcriptional nuclear factor, NF-κB; (d) DCPIP can attenuate or completely inhibit VEGF-induced angiogenesis in the chick chorioallantoic membrane; (e) DCPIP at concentrations higher than 6 μg/ml induces apoptosis in HCT116 cells as confirmed by detection of caspase-3 and PARP degradation; and (f) DCPIP encapsulated in nanoparticles is equally or more effective than free DCPIP in exhibiting the aforementioned properties (a-e) in addition to reducing the expression of COX-2, and pro-inflammatory proteins IL-6 and IL-8.ConclusionsWe propose that, DCPIP may serve as a potent tool to prevent or disrupt the processes of cell proliferation, tissue angiogenesis and inflammation by directly or indirectly targeting expression of specific cellular factors. We also propose that the activities of DCPIP may be long-lasting and/or enhanced if it is delivered enclosed in specific nanoparticles.

Highlights

The redox dye, DCPIP, has recently shown to exhibit anti-melanoma activity in vitro and in vivo
We demonstrate that (a) DCPIP enclosed in PLGA nanoparticles (DCPIP NPs) exhibits higher antiproliferative activity than free DCPIP in cultured cancer HCT116 cells; (b) DCPIP NPs is or more potent than free DCPIP in the ability to down-regulate proangiogenic and pro-inflammatory factors, vascular endothelial growth factor (VEGF), COX-2, IL-6 and IL-8, in cultured human colon cancer cells; (c) DCPIP and DCPIP NPs are effective in inhibiting VEGF-induced angiogenesis in ovo; (d) PLGA NPs can serve as a useful vehicle for the delivery of DCPIP; and (e) DCPIP causes apoptosis of HCT116 cells at concentrations ≥ 6 μg/ml
The PLGA NPs appear as spherically shaped particles, by scanning electron microscopy, consistent with published reports on PLGA NPs constructed by the double emulsion method (Figure 1A)

Summary

Introduction

The redox dye, DCPIP, has recently shown to exhibit anti-melanoma activity in vitro and in vivo. There is increasing evidence that synthetic nanoparticles can serve as highly efficient carriers of drugs and vaccines for treatment of various diseases. COX-2 over-expression has been detected in several types of human cancers such as colon, breast, prostate, lung, pancreas and leukemias and appears to control many cellular processes [10]. Because of their roles in angiogenesis, carcinogenesis, and apoptosis, VEGF and COX-2 are excellent targets for developing new drugs with selectivity for prevention and/or treatment of human cancers

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