Incorporation of branched-chain fatty acid into cellular lipids and caspase-independent apoptosis in human breast cancer cell line, SKBR-3

BACKGROUND: 13-Methyltetradecanoic acid (13-MTD), an iso-C15 branched- chain saturated fatty acid, has been shown to induce apoptotic cell death of numerous human cancer cells. However, the mechanism for the induction of apoptosis has not been fully understood. This study described the incorporation of 13-MTD into cellular lipid of SKBR-3 breast cancer cells and apoptosis related event to gain more insight into the mechanism action of this fatty acid. RESULTS: Treatment of SKBR-3 cells with 13-MTD lowered the cell viability and induced apoptosis. Proportion of 13-MTD in the glycerolipids increased to saturation level within 6 hours. Triacylglycerol contained 13-MTD in higher concentration than phospholipid with positional preference to sn-2. 13-MTD caused no changes in the caspase activity and its gene expression. Furthermore, addition of caspase-inhibitor to culture medium did not prevent the cells from the cytotoxicity of 13-MTD. No-increase in the cellular calcium level was also noted with 13-MTD treatment. However, 13-MTD disrupted the mitochondrial integrity in 4 hours, and increased the nuclear translocation of apoptosis inducing factor. CONCLUSION: These results showed that 13-MTD disrupted the mitochondrial integrity, and induced apoptosis via caspase-independent death pathway

Salicylic Acid: An All-Rounder in Regulating Abiotic Stress Responses in Plants

Salicylic acid (SA) is an endogenous growth regulator of phenolic nature and also a signaling molecule, which participates in the regulation of physiological processes in plants such as growth, photosynthesis, and other metabolic processes. Several studies support a major role of SA in modulating the plant response to various abiotic stresses. It is a well-founded fact that SA potentially generates a wide array of metabolic responses in plants and also affects plant-water relations. This molecule also found to be very active in mitigating oxidative stress under adverse environmental conditions. Since abiotic stress remained the greatest constraints for crop production worldwide, finding effective approaches is an important task for plant biologists. Hence, understanding the physiological role of SA would help in developing abiotic stress tolerance in plants. In this chapter, we will shed light on the recent progress on the regulatory role of SA in mitigating abiotic stress

Effect of purified soluble polysaccharides extracted from gray oyster mushroom [Pleurotus sajor-caju (Fr.) Sing.] on 3t3-L1 adipocytes

Functional mushroom polysaccharides have been known to the Asian traditional medicine for many years. The anti-obesity activity of mushroom polysaccharides has been illustrated both in vivo and in vitro. However, the effect of pure polysaccharides on isolated fat cells has not been demonstrated. In this study, we used hot water and ammonium oxalate to extract polysaccharides from gray oyster mushroom [Pleurotus sajor-caju (Fr.) Sing.] and subsequently purified with enzymatic digestion, solvent extraction and ion-exchange chromatography. One of the fractions, 7S1-1, has the highest yield and purity and contains polysaccharides with the molecular weight around 500 kDa. In addition, Fourier transformed infrared spectroscopy (FTIR) and monosaccharide composition analyses showed that this 7S1-1 sample contains mostly β-glucan and some mannan. We find that the 7S1-1 fraction does not affect the total amount of triglycerides in the 3T3-L1 adipocytes but promotes a release of glycerol of the fat cells, suggesting that the fraction does not inhibit adipogenesis but stimulates lipolysis. Laminarin, a small β-glucan, confers similar results to the 7S1-1 sample, but it could not stimulate lipolysis as well as the 7S1-1 sample. Therefore, these results suggest a potential anti-obesity activity of the mushroom polysaccharides

Tumor-selective cytotoxicity of nitidine results from its rapid accumulation into mitochondria

We identified a nitidine- (NTD-) accumulating organelle and evaluated the net cytotoxicity of accumulated NTD. To evaluate tumor cell selectivity of the drug, we evaluated its selective cytotoxicity against 39 human cancer cell lines (JFCR39 panel), and the profile was compared with those of known anticancer drugs. Organelle specificity of NTD was visualized using organelle-targeted fluorescent proteins. Real-time analysis of cell growth, proliferation, and cytotoxicity was performed using the xCELLigence system. Selectivity of NTD in the JFCR39 panel was evaluated. Mitochondria-specific accumulation of NTD was observed. Real-time cytotoxicity analysis suggested that the mechanism ofNTD-induced cell death is independent of the cell cycle. Short-termtreatment indicated that this cytotoxicity only resulted from the accumulation of NTD into the mitochondria. The results from the JFCR39 panel indicated that NTD-mediated cytotoxicity resulted fromunique mechanisms compared with those of other known anticancer drugs. These results suggested that the cytotoxicity of NTD is only induced by its accumulation in mitochondria.Thedrug triggered mitochondrial dysfunction in less than 2 h. Similarity analysis of the selectivity of NTD in 39 tumor cell lines strongly supported the unique tumor cell specificity of NTD. Thus, these features indicate that NTD may be a promising antitumor drug for new combination chemotherapie

Effect of Mukitake mushroom (Panellus serotinus) on the pathogenesis of lipid abnormalities in obese, diabetic ob/ob mice.

Background: Various mushrooms have been used in folk medicine for the treatment of lifestyle diseases in eastern countries, and several compounds that modulate the immune system, lower blood lipid levels, and inhibit tumor and viral action have been isolated. The fruiting body of Panellus serotinus (Mukitake) is recognized in Japan as one of the most delicious edible mushrooms, and previous studies have demonstrated that the dietary intake of powdered whole Mukitake or Mukitake extracts prevents the development of non-alcoholic fatty liver disease (NAFLD) in leptin-resistant db/db mice. In the present study, we evaluated the effect of the Mukitake diet on the pathogenesis of metabolic disorders in leptin-deficient ob/ob mice. Results: After 4 weeks of feeding, hepatomegaly, hepatic lipid accumulation, and elevated hepatic injury markers in the serum were markedly alleviated in Mukitake-fed ob/ob mice compared with control mice. Moreover, the mild hyperlipidemia in control ob/ob mice was attenuated and the elevated atherogenic index was reduced in Mukitake-fed ob/ob mice. These effects were partly attributable to the suppression of hepatic lipogenic enzyme activity due to the Mukitake diet. Conclusion: The current results showed that Mukitake supplementation is beneficial for the alleviation of NAFLD and dyslipidemia in obese, diabetic ob/ob mic

Triterpenoid modulates the salt tolerance of lanosterol synthase deficient Saccharomyces cerevisiae, GIL77

This study examined the effect of triterpenoid on the salt tolerance of lanosterol synthase deficient yeast mutant GIL77. The expression of the triterpenoid synthase gene under GAL1 promoter in GIL77 increased the triterpenoid concentration of both whole cell and plasma membrane fractions. Without the induction of the genes, the growth curve of BgbAS or RsM1 transformant depicted patterns similar to control cells in both the presence and absence of salt with growth inhibition at 500 mM NaCl. The induction of BgbAS and RsM1 gene expression slightly repressed growth compared with control cells in the absence of NaCl. The growth of GIL77 was significantly suppressed by the expression of BgbAS or RsM1 under salinity conditions. Of the triterpenoid synthase genes, BgbAS rather than RsM1 was found to strongly inhibit the growth of GIL77 cells under salt stressed conditions. The expression of the triterpenoid synthase gene in GIL77 also influenced their tolerance to other abiotic stresses. In contrast to the endogenous synthesis, the exogenous supply of triterpenoid in the culture medium appeared to occur in the plasma membrane fraction and enhanced the salt tolerance of GIL77. This study thus discussed the physiological significance of triterpenoid in relation to its possible role in modulating salt tolerance