Background:Cancer is one of the major heterogeneous disease with high morbidity and mortality with poor prognosis. Elevated levels of reactive oxygen species (ROS), alteration in redox balance, and deregulated redox signaling are common hallmarks of cancer progression and resistance to treatment. Mitochondria contribute mainly in the generation of ROS during oxidative phosphorylation. Elevated levels of ROS have been detected in cancers cells due to high metabolic activity, cellular signaling, peroxisomal activity, mitochondrial dysfunction, activation of oncogene, and increased enzymatic activity of oxidases, cyclooxygenases, lipoxygenases, and thymidine phosphorylases. Cells maintain intracellular homeostasis by developing an immense antioxidant system including catalase, superoxide dismutase, and glutathione peroxidase. Besides these enzymes exist an important antioxidant glutathione and transcription factor Nrf2 which contribute in balancing oxidative stress. Reactive oxygen species–mediated signaling pathways activate pro-oncogenic signaling which eases in cancer progression, angiogenesis, and survival. Concomitantly, to maintain ROS homeostasis and evade cancer cell death, an increased level of antioxidant capacity is associated with cancer cells.Conclusions:This review focuses the role of ROS in cancer survival pathways and importance of targeting the ROS signal involved in cancer development, which is a new strategy in cancer treatment.

Exosomes are cell-cell communicators emerging as a new paradigm for noninvasive diagnosis and prognosis of treatment response. Exosomal tetraspanin proteins like CD63, CD9 and CD81 play a critical role in sorting, selective recruitment of biomolecules, target selection, cell-specific entry, capturing, angiogenesis and vasculogenesis. These tetraspanins are being used as markers for oral, colorectal and colon cancers and glioblastoma. However, exosomal markers with robust specificity for early detection of carcinomas are the furthest along. EXO CARTA database shows the presence of CD151 in exosomes of colorectal, melanoma, ovarian and prostate cancers. CD151 preferentially targets exosomes to lung, lymph node and stroma cells. The present review discussed the possible role of tetraspanins in the formation, cargo selection, target selection and uptake of exosomes and suggests exciting new directions for future research.

PurposeLipid rafts are cholesterol enriched microdomains that colocalize signaling pathways involved in cell proliferation, metastasis, and angiogenesis. We examined the effect of methyl-β-cyclodextrin (MβCD)-mediated cholesterol extraction on the proliferation, adhesion, invasion, and angiogenesis of triple negative breast cancer (TNBC) cells.MethodsWe measured cholesterol and estimated cell toxicity. Detergent resistant membrane (DRM) and non-DRM fractions were separated using the OptiPrep gradient method. Cell cycles stages were analyzed by flow cytometry, apoptosis was assessed using the TdT-mediated dUTP nick end-labeling assay, and metastasis was determined using a Matrigel invasion assay. Neo-vessel pattern and levels of angiogenic modulators were determined using an in vitro angiogenesis assay and an angiogenesis array, respectively.ResultsThe present study found that the cholesterol-depleting agent MβCD, efficiently depleted membrane cholesterol and caused concentration dependent (0.1–0.5 mM) cytotoxicity compared to nystatin and filipin III in TNBC cell lines, MDA-MB 231 and MDA-MB 468. A reduced proportion of caveolin-1 found in DRM fractions indicated a cholesterol extraction-induced disruption of lipid raft integrity. MβCD inhibited 52% of MDA-MB 231 cell adhesion on fibronectin and 56% of MDA-MB 468 cell adhesion on vitronectin, while invasiveness of these cells was decreased by 48% and 52% respectively, following MβCD treatment (48 hours). MβCD also caused cell cycle arrest at the G2M phase and apoptosis in MDA-MB 231 cells (25% and 58% cells, respectively) and in MDA-MB 468 cells (30% and 38% cells, respectively). We found that MβCD treated cells caused a 52% and 58% depletion of neovessel formation in both MDA-MB 231 and MDA-MB 468 cell lines, respectively. This study also demonstrated that MβCD treatment caused a respective 2.6- and 2.5-fold depletion of tyrosine protein kinase receptor (TEK) receptor tyrosine kinase levels in both TNBC cell lines.ConclusionMβCD-induced cholesterol removal enhances alterations in lipid raft integrity, which reduces TNBC cell survival.

BackgroundHydrogen peroxide is continuously generated in living cells through metabolic pathways and serves as a source of reactive oxygen species. Beyond the threshold level, it damages cells and causes several human disorders, including cancer.MethodsEffect of isolated 3-O-methyl quercetin and kaempferol on H2O2 induced cytotoxicity, ROS formation, plasma membrane damage, loss of mitochondrial membrane potential, DNA damage was evaluated in normal liver and lung cells. The RT-PCR analysis used to determine Nrf 2 gene expression. Calorimetric ELISA was used to determine Nrf2 and p-38 levels. Expression of SOD and catalase was analyzed by Western blot analysis.ResultsThe present study isolated 3-O-methyl quercetin and kaempferol from the stem bark. They protected normal lung and liver cells from H2O2 induced cytotoxicity, ROS formation, membrane damage and DNA damage. Pre-treatment with 3-O-methyl quercetin and kaempferol caused translocation of Nrf2 from cytosol to nucleus. It also increased expression of p-p38, Nrf2, SOD and catalase in H2O2 treated lung and liver cells.ConclusionThe flavonoids isolated from S. anacardium significantly reduced H2O2 induced stress and increased expression of Nrf2, catalase and superoxide dismutase-2 indicating cytoprotective nature of 3-O-methylquercetin and kaempferol.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1354-z) contains supplementary material, which is available to authorized users.

Triple-negative breast cancer (TNBC) is the most aggressive and prevalent subtype of breast cancer in women worldwide. Currently, chemotherapy remains the main modality for the treatment at an early stage, as there is no approved targeted therapy for early TNBC. In this review, we investigate the use of microRNAs (miRNAs), which play a key role in the post-transcriptional regulation of genes involved in the key biological processes, namely proliferation, differentiation, angiogenesis, migration, apoptosis, and carcinogenesis. Here, we emphasize the importance of the recent advances related to miRNAs, involving diagnosis, prognosis, and treatment of TNBC. We focus on the development, optimization, and stabilization of miRNA-based drugs; improvement of miRNA delivery; and control of the off-target effects of miRNA therapeutics. We speculate as to which features may present themselves as promising approaches in the treatment of TNBC. Keywords TNBC. miRNA. Cancer biomarkers. miRNA-based therapy Abbreviations Bmi 1 B lymphoma Mo-MLV insertion region 1 homolog CSC Cancer stem cells ER Estrogen receptor HER 2 Human epidermal growth factor receptor 2 PR Progesterone receptor TNBC Triple-negative breast cancer ts-microRNA Tumor suppressor microRNA Highlights • Patients diagnosed with negative ER, PR, and HER 2 are the most prevalent subtypes of breast cancer with limited targeted therapy. • miRNAs play a key role in regulating the gene expression of the key biological processes including proliferation, differentiation, angiogenesis, migration, and apoptosis. The involvement of miRNA has also been identified in carcinogenesis. • In TNBC, miRNAs make major contributions to the diagnosis, prognosis, and treatment. • We suggest that miRNA-based therapeutics could be a promising approach in the treatment of TNBC.