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Resveratrol (RES) is a natural polyphenol having anti-proliferative activity against breast cancer cells. RES in combination with other chemo modulatory agents, minimizes toxicity and increases efficacy of the treatment. Salinomycin (SAL), a monocarboxylic polyether ionophore is known for selectively targeting breast cancer stem cells. Purpose of the present study was to investigate whether RES in combination with SAL exerts synergistic anti-proliferative activity on breast cancer cells. We further evaluated the molecular mechanism behind SAL and RES mediated cell death. Cytotoxicity assay was performed to determine 50% inhibitory concentration (IC50) of SAL and RES in different human breast cancer cells (HBCCs). Drug synergism and combination index (CI) were calculated using CompuSyn software and effects of synergistic combinations (CI < 1) involving lower doses of SAL and RES were selected for further studies. This combination significantly induced apoptosis in HBCCs without affecting non tumorigenic human breast epithelial cells MCF-10A. Co-treatment enhanced apoptosis in MCF-7 cells via reactive oxygen species (ROS) mediated mitochondrial dysfunction. Oxidative stress disrupt redox homeostasis which altered antioxidant enzymes viz. CuZn Superoxide dismutase (SOD), MnSOD and catalase. Additionally, combination altered nuclear morphology, enhanced PARP cleavage and led to caspase activation. SAL and RES also synergistically modulated MAPK pathway. Study suggests that SAL and RES offer a novel combination approach for the treatment of breast cancer.

Aim: The purpose of present work was to utilize lignocellulosic forest waste for cost-effective production of commercially important enzymes i.e. cellulase and xylanase by employing co-culture of Aspergillus niger F 7 and Fusarium oxysporum F 8 in solid state fermentation (SSF). Material and Methods: Fungal strains i.e. A. niger F 7 and F. oxysporum F 8 isolated from degrading forest litter were used as co-culture and their enzyme biosynthesis on forest waste was noticed. The prominent forest wastes i.e. Toona ciliata, Celtris australis, Cedrus deodara and Pinus roxburghii were procured from local forest and alkali (NaOH) pretreatment was given to these lignocellulosic substrates to simplify the crystalline cellulose present in them for higher yield of enzymes by fungal isolates. Two types of moistening agents i.e. tap water and modified basal salt medium (BSM) were used in the substrate in the ratio of 1:2 to evaluate their effect on enzyme production under SSF.

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