PurposeThe unmanageable side effects caused by current chemotherapy regimens to treat cancer are an unresolved problem. Although many phytonutrients are useful as chemoprevention without side effects, their effects are slower and smaller than conventional chemotherapy. In the present work, we examined the cumulative effect of two phytonutrients, curcumin and citral, on breast cancer cell lines and compared their effect with the known chemotherapy regimen of cyclophosphamide, methotrexate, and 5-fluorouracil.MethodsUsing cultured breast cancer and normal epithelial cells, the cytotoxic and apoptotic effect of curcumin and citral was evaluated in vitro. The synergistic effect of curcumin and citral was calculated by a combination index study using the method by Chou and Talalay. Cell death pathways and mechanisms were analyzed by measuring intracellular reactive oxygen species (ROS) and apoptotic protein levels.ResultsCurcumin and citral caused dose and time dependent cell death and showed a synergistic effect at effective concentration EC50 and above concentrations in breast cancer cells without disturbing normal breast epithelial cells. With combination curcumin and citral treatment, apoptosis induction and cell cycle arrest at G0/G1 phase in breast cancer cells were observed. Curcumin and citral generated ROS and activated p53 and poly (ADP-ribose) polymerase-1 mediated apoptotic pathways.ConclusionThe results of this study suggest that curcumin and citral in combination may be a useful therapeutic intervention for breast cancer.

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A series of 1,3,5-trisubstituted pyrazolines based homoleptic Ru(III) complexes of type [Ru(L 1-7 ) 3 ]$(PF 6 ) 3 (L 1-7 ¼ pyrazoline ligands) have been synthesized and characterized by elemental analysis, electronic spectroscopy, conductance measurements, thermogravimetric analysis (TGA), electron paramagnetic resonance (EPR), fourier transform infrared (FT-IR) spectroscopy and liquid chromatography mass spectroscopy (LC-MS). Octahedral geometry around ruthenium has been assigned in all complexes using EPR and electronic spectral analysis. All complexes have been investigated for their interaction with Herring Sperm (HS) DNA utilizing an absorption titration (K b ¼ 2.42-6.07 Â 10 5 M À1 ) and viscosity measurement study. The studies suggest the classical intercalative mode of binding. The DNA-binding property of the Ru(III) complexes was also investigated theoretically using a molecular docking study and suggests an intercalation binding mode between the complex and nucleotide base pairs. A cleavage study on pUC19 DNA has been performed by agarose gel electrophoresis. The results indicated that the Ru(III) complexes can more effectively promote the cleavage of plasmid DNA. The free ligands and their complexes have been evaluated for cytotoxicity activity against S. pombe cells at a cellular level. A comparative study of cellular level cytotoxicity values of the all compounds indicates that the metal complexes show better activity against S. pombe cells compared to the pyrazoline ligands. The complexes have been screened for their in vitro antibacterial activity against two Gram(+ve) and three Gram(Àve) microorganisms. Ru(III) complexes are good in vitro cytotoxic agents and 50% lethal concentration (LC 50 ) values are in range of 5.296-7.925 mg mL À1 . All newly synthesized Ru(III) complexes have been also evaluated for their in vitro antimalarial activity against Plasmodium falciparum strain [inhibition concentration (IC 50 ) ¼ 0.54-0.92 mg mL À1 ].

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