Physiochemical characterization and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay suggest that polysorbate 80 has the dual capability of being a stabilizer and a surface modifier in addition to having better drug entrapment properties than Pluronic® 188. Disulfiram, the drug that was loaded on these NPs, is also observed for the first time to show significant anticancer potential against hepatocellular carcinoma (Hep3B) cell lines.
Understanding the influence of ubiquitously present plant steroids on mammalian cell biology is currently of interest. Feedback inhibition of HMGCoA reductase (HMGCR) catalytic activity in the transformation of HMG-CoA to mevalonate is a significant regulatory step in sterol biosynthetic pathway. To assess the role of dietary steroids in this biochemical transformation, the phytosteroid isoform 28-homobrassinolide (28-HB), 90 % pure, obtained from Godrej Agrovet (India) was used to determine its effect on mammalian HMG-CoA reductase. Photometric assay of pure human and select rat tissue HMGCR post 28-HB oral feed, PCR-HMGCR gene expression, and in silico docking of 28-HB and HMGCoA on HMGCR protein template were carried out. Using an oral feed regimen of pure 28-HB, we noted a decrease of 16 % in liver, 17.1 % in kidney and 9.3 % in testicular HMGCR enzyme activity, 25 % in HMGCR gene expression and 44 % in the activity of pure human HMGCR due to this plant oxysterol. In silico docking studies yielded binding metrics for 28-HB-HMGCR lower than for HMGCoA-HMGCR, indicating stronger binding of HMGCR by this ligand. 28-HB exerts differential effects on rat tissue HMGCR, down regulates liver HMGCR gene expression and significantly inhibits HMGCR activity.
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Drug resistance by the cancer cells towards current chemotherapeutic approaches poses a great challenge. In the present study, an Indole analogue of a well-known plant derived anticancer molecule, Curcumin, was tested for its multidrug resistance (MDR) reversing potential in induced multi drug resistant A549 cell line. Human lung cancer cell line A549 was made multidrug resistant (MDR) by prolonged treatment with low dosage of Docetaxel, an established anticancer drug. The MDR induction was confirmed by morphological evidence, Hoechst 33342 staining, MTT assay, Rhodamine123 and RT-PCR of ABCB1 gene. The induced MDR A549 cells exhibited significant increase in the gene expression of ABCB1 gene at transcriptional level. Retention and efflux studies with P-glycoprotein (P-gp) substrate Rh123 indicated that indole curcumin inhibited P-gp mediated efflux of Rhodamine. Furthermore, treatment of MDR A549 cells with indole curcumin showed down-regulation of gene expression of ABCB1 and COX2. This was also confirmed from the decreased protein level expression of COX2. In conclusion, the results of the present study indicate that indole curcumin reverses multi drug resistance by downregulating the expression of ABCB1 and COX2 genes. Thus, indole curcumin may act as a potent modulator for ABCB1 and COX2 mediated MDR in lung cancer.
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