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Variation in biological activities of curcumin and ferrocene containing curcumin analogue in Hepa 1-6 cell culture

Malignant transformation of normal hepatocytes into hepatocellular carcinoma occurs through repetitive liver cell injury manifesting as inflammation, oxidative DNA and protein damage, loss of cell cycle control, avoidance of apoptosis, and aberrant proliferation. Curcumin, a natural substance from curcuma displays antioxidant, anti-inflammatory, and anti-carcinogenic properties. The aim of the study was to in vitro (against mouse hepatoma cells Hepa 1-6) investigate toxicity and antiproliferative effects of curcumin and ferrocene-containing curcumin analogue (FCA) in which one benzylidene group of curcumin is replaced by ferrocene. Curcumin and FCA were tested in the range 1-100 mol/L and cell viability was monitored by two in vitro cytotoxicity assays, while intracellular effects were assessed by cytofluorimetric analysis. Concentration-dependent growth inhibition in Hepa 1-6 cell line after 48 h curcumin exposure was confirmed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and Trypan Blue (TB) methods with significant effects in concentrations ≥2.5 mol/L and ≥1 mol/L, respectively. In relation to curcumin-treated cells, the cell culture treated with FCA showed a higher viability and proliferation rate. The inhibitory effects of FCA were observed at concentrations ≥35 mol/L determined with MTT and ≥75 mol/L with TB assay. Cytofluorimetric analysis confirmed notably elevated apoptotic cell fraction (late apoptotic/dead cells – 73 % ; early apoptotic cells – 19 %) after treatment with 100 mol/L curcumin vs. control/untreated cells, while FCA did not affect cell viability (level of apoptotic and necrotic cell death was low ; early and late apoptosis – 14 %). These findings suggest that curcumin, but not FCA, alters cellular progression and may be effective in suppressing liver malignant progression.

apoptosis ; bioorganometallic derivatives ; cell viability ; curcuminoids ; nutrition

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