Indole curcumin combats metastatic HBV-positive hepatocellular carcinoma by inhibiting cell proliferation, migration, and matrix metalloproteinase-9 activity

Background: Chemical modification of the natural products and molecules can lead us toward drugs with lesser off-target effects for chemotherapeutic use against cancers. In this study, we explored the effect of an indole analog of the molecule curcumin, for the first time against HBV-positive hepatocellular carcinoma (HCC) cells in vitro. Materials and Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase assays were used to measure the cytotoxic effects of indole curcumin against Hep3B cells. The mode of cell death was established through acridine orange/ethidium bromide fluorescence staining, propidium iodide fluorescence staining, and the comet assay. The effect of the compound on cell migration behavior was studied through wound healing assay, whereas the effect on matrix metalloproteinase (MMP) activity was evaluated using gelatin zymography. In silico molecular docking was performed to predict the affinity of indole curcumin toward probable intracellular interacting partners. Results and Discussion: Indole curcumin had an antiproliferative effect on Hep3B cells, induced apoptotic mode of cell death, inhibited cell migration in time- and dose-dependent assays, and decreased MMP-9 activity levels. Molecular docking results suggest that the interaction of PI3K with indole curcumin may have led to downregulation of MMP-9 expression, thereby contributing to the overall reduction in MMP-9 activity. Conclusion: Our study establishes that indole curcumin is an effective cytotoxic and antimetastatic agent against hepatitis virus-B positive HCC cells. Hence, it can be a possible candidate for the treatment of hepatocarcinoma induced/promoted by the presence of chronic hepatitis B infection.