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Cancer diagnosis is currently undergoing a paradigm shift with the incorporation of molecular biomarkers as part of routine diagnostic panel. The molecular alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs are recently discovered small non-coding endogenous single-stranded RNAs that critically regulates the development, invasion and metastasis of cancers. They are altered in cancers and have the potential to serve as diagnostic markers for cancer. Moreover, deregulating their activity offers novel cancer therapeutic approaches. The availability of high throughput techniques for the identification of altered cellular molecules allowed their use in cancer diagnosis. Their application to a variety of body specimens from blood to tissues has been helpful for appreciating their use in the clinical context. The development of innovative antibodies for immunohistochemical detection of proteins also assists in diagnosis and risk stratification. Overall, the novel cancer diagnostic tools have extended their application as prognostic risk factors and can be used as targets for personalized medicine. [ABSTRACT FROM AUTHOR]

Garcinol, obtained from Garcinia indica, has exhibited some promising anticancer activity. In particular, our earlier work has demonstrated its ability to inhibit cell proliferation and induction of apoptosis in multiple cancer cell lines representative of breast, prostate, as well as pancreatic cancers. However, its exact mechanism of action remains largely unclear. Here we show that garcinol also targets signal transducer and activator of transcription-3 (STAT-3) signaling pathway. STAT-3 is frequently found to be activated in many cancer types and this is the first report on such action of garcinol leading to its anticancer effects. Garcinol inhibited total, as well as phosphorylated, STAT-3 in breast, prostate and pancreatic cancer cell lines and was also found to inhibit cell invasion of all the cancer cell lines tested. STAT-3 phosphorylation was inhibited by garcinol in a dose-dependent manner. We also observed an inhibitory effect of garcinol on IL-6-induced STAT-3 phosphorylation and production of urokinase-type plasminogen activator, vascular endothelial growth factor and matrix metalloproteinase-9, which might explain the reduced invasion and aggressiveness of cells treated with garcinol. The results were further verified in vivo using MDA-MB-231 breast cancer mouse xenograft model where administration of garcinol significantly inhibited tumor growth, and western blot analysis of remnant tumor lysates showed reduced STAT-3 expression and activation. These results suggest that garcinol may have translational potential as chemopreventive or therapeutic agent against multiple cancers and inhibition of STAT-3 signaling pathway is one of the mechanisms by which garcinol exerts its anticancer effects. [ABSTRACT FROM PUBLISHER]

Tumor hypoxia with deregulated expression of hypoxia inducing factor (HIF) and its biological consequence leads to poor prognosis of patients diagnosed with solid tumors, resulting in higher mortality, suggesting that understanding of the molecular relationship of hypoxia with other cellular features of tumor aggressiveness would be invaluable for developing newer targeted therapy for solid tumors. Emerging evidence also suggest that hypoxia and HIF signaling pathways contributes to the acquisition of epithelial-to-mesenchymal transition (EMT), maintenance of cancer stem cell (CSC) functions, and also maintains the vicious cycle of inflammation, all of which contribute to radiation therapy and chemotherapy resistance. However, the detailed mechanisms by which hypoxia/HIF drive these events are not fully understood. Here, we have shown that hypoxia leads to increased expression of VEGF, IL-6, and CSC marker genes such as Nanog, Oct4 and EZH2, and also increased the expression of miR-21, an oncogenic miRNA, in prostate cancer (PCa) cells (PC-3 and LNCaP). The treatment of PCa cells with CDF, a novel Curcumin-derived synthetic analogue previously showed anti-tumor activity in vivo, inhibited the productions of VEGF and IL-6, and down-regulated the expression of Nanog, Oct4, EZH2 mRNAs, as well as miR-21 under hypoxic condition. Moreover, CDF treatment of PCa cells led to decreased cell migration under hypoxic condition. Taken together, these results suggest that the anti- tumor effect of CDF is in part mediated through deregulation of tumor hypoxic pathways, and thus CDF could become useful for cancer therapy. [ABSTRACT FROM AUTHOR]