Prostate cancer is the most commonly diagnosed cancer in men with African American men disproportionally suffering from the burden of this disease. Biomarkers that could discriminate indolent from aggressive and drug resistance disease are lacking. MicroRNAs are small non-coding RNAs that affect numerous physiological and pathological processes, including cancer development and have been suggested as biomarkers and therapeutic targets. In the present study, we investigated the role of miR-214 on prostate cancer cell survival/migration/invasion, cell cycle regulation, and apoptosis. miR-214 was differentially expressed between Caucasian and African American prostate cancer cells. Importantly, miR-214 overexpression in prostate cancer cells induced apoptosis, inhibiting cell proliferation and colony forming ability. miR-214 expression in prostate cancer cells also inhibited cell migration and 3D spheroid invasion. Mechanistically, miR-214 inhibited prostate cancer cell proliferation by targeting protein tyrosine kinase 6 (PTK6). Restoration of PTK6 expression attenuated the inhibitory effect of miR-214 on cell proliferation. Moreover, simultaneous inhibition of PTK6 by ibrutinib and miR-214 significantly reduced cell proliferation/survival. Our data indicates that miR-214 could act as a tumor suppressor in prostate cancer and could potentially be utilized as a biomarker and therapeutic target.

Long noncoding RNAs (lncRNAs) are transcripts greater than 200 nucleotides that do not code for proteins but regulate gene expression. Recent studies indicate that lncRNAs are involved in the modulation of biological functions in human disease. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) encodes a lncRNA from the opposite strand of KCNQ1 in the CDKN1C/KCNQ1OT1 cluster that is reported to play a vital role in the development and progression of cancer. KCNQ1OT1 regulates cancer cell proliferation, cell cycle, migration and invasion, metastasis, glucose metabolism, and immune evasion. The aberrant expression of KCNQ1OT1 in cancer patients is associated with poor prognosis and decreased survival. This review summarizes recent literature related to the biological functions and molecular mechanisms of KCNQ1OT1 in various human cancers, including colorectal, bladder, breast, oral, melanoma, osteosarcoma, lung, glioma, ovarian, liver, acute myeloid leukemia, prostate, and gastric. We also discuss the role of KCNQ1OT1 as a promising diagnostic biomarker and a novel therapeutic target in human cancers.

A novel complex, [Cu(acetylethTSC)Cl]Cl•0.25C2H5OH 1 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide), was shown to have anti-proliferative activity against various colon and aggressive breast cancer cell lines. In vitro studies showed that complex 1 acted as a poison inhibitor of human topoisomerase IIα, which may account for the observed anti-cancer effects.

Fungal metabolites continue to show promise as a viable class of anticancer agents. In the present study, we investigated the efficacy of the fungal metabolite, fusarochromanone (FC101), for its antitumor activities in glioblastomas, which have a median survival of less than two years and a poor clinical response to surgical resection, radiation therapy and chemotherapy. Using clinically applicable doses, we demonstrated that FC101 induced glioblastoma apoptotic cell death via caspase dependent signaling, as indicated by the cleavage of poly(ADP-ribose) polymerase, glioblastoma (PARP). FC101 also induced differential reactive oxygen species (ROS) levels in glioblastoma cells, contrasting a defined role of oxidative stress in apoptotic cell death observed with other fungal metabolites. Furthermore, the antitumorigenic effects of FC101 on tumor cell migration were assessed. Cell migration assays revealed that FC101 significantly reduced the migratory capacity of glioblastomas, which are incredibly invasive tumors. Taken together, the present study establishes FC101 as a candidate anticancer agent for the cooperative treatment of glioblastomas.

Rosehips are blossoms from the wild rose (Rosa canina) and are commonly used as an herbal remedy. Previous reports have shown that extracts made from rosehip plants are able to reduce cell proliferation of cancer cells. In this study, we investigated the efficacy of rosehip extracts in preventing cell proliferation of three human glioblastoma cell lines A-172, U-251 MG and U-1242 MG cell lines. Each of the glioblastoma cell lines treated with rosehip extracts (1 mg/mL -25 ng/mL) demonstrated a significant decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when inhibitors of the MAPK (U0126, 10 µM) or AKT (LY294002, 20 µM) signaling pathways were utilized. Additionally, pretreatment of the these cell lines with Rosehip extracts (1 mg/mL -25 ng/mL) selectively decreased AKT, MAPK, and p70S6K phosphorylation suggesting these extracts prevent glioblastoma multiforme cell proliferation by blocking both the MAPK and AKT signaling mechanisms. Results from colorimetric cell death assays, cell cycle analysis by flow cytometry, as well as western blot studies demonstrate that rosehip extracts inhibit cell proliferation but do not promote apoptosis. Moreover, rosehip extracts were able to increase the efficacy of Temozolomide, a chemotherapeutic agent used to treat patients with glioblastomas. Surprisingly, rosehip extracts demonstrated a greater inhibition of cell proliferation than in combination with Temozolomide (100 µM) or Temozolomide as a single agent. Taken together these data suggest that rosehip extracts are capable of decreasing glioblastoma cell proliferation without promoting apoptosis and demonstrate a greater cell proliferation inhibitory effect than Temozolomide. More importantly, rosehip extracts may serve as an alternative or compliment to current chemotherapeutic regimens for glioblastomas.

MicroRNAs (miRNAs) are single-stranded non-coding RNA molecules that play a regulatory role in gene expression and cancer cell signaling. We previously identified miR-628-5p (miR-628) as a potential biomarker in serum samples from men with prostate cancer (PCa) (Srivastava et al. in Tumour Biol 35:4867–4873, 10.1007/s13277-014-1638-1, 2014). This study examined the detailed cellular phenotypes and pathways regulated by miR-628 in PCa cells. Since obesity is a significant risk factor for PCa, and there is a correlation between levels of the obesity-associated hormone leptin and PCa development, here we investigated the functional relationship between leptin and miR-628 regulation in PCa. We demonstrated that exposure to leptin downregulated the expression of miR-628 and increased cell proliferation/migration in PCa cells. We next studied the effects on cancer-related phenotypes in PCa cells after altering miR-628 expression levels. Enforced expression of miR-628 in PCa cells inhibited cell proliferation, reduced PCa cell survival/migration/invasion/spheroid formation, and decreased markers of cell stemness. Mechanistically, miR-628 binds with the JAG1-3′UTR and inhibits the expression of Jagged-1 (JAG1). JAG1 inhibition by miR-628 downregulated Notch signaling, decreased the expression of Snail/Slug, and modulated epithelial-mesenchymal transition and invasiveness in PC3 cells. Furthermore, expression of miR-628 in PCa cells increased sensitivity towards the drugs enzalutamide and docetaxel by induction of cell apoptosis. Collectively our data suggest that miR-628 is a key regulator of PCa carcinogenesis and is modulated by leptin, offering a novel therapeutic opportunity to inhibit the growth of advanced PCa.

Abnormal expression of microRNA miR-214-3p (miR-214) is associated with multiple cancers. In this study, we assessed the effects of CRISPR/Cas9 mediated miR-214 depletion in prostate cancer (PCa) cells and the underlying mechanisms. Knockdown of miR-214 promoted PCa cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and increased resistance to anoikis, a key feature of PCa cells that undergo metastasis. The reintroduction of miR-214 in miR-214 knockdown cells reversed these effects and significantly suppressed cell proliferation, migration, and invasion. These in vitro studies are consistent with the role of miR-214 as a tumor suppressor. Moreover, miR-214 knockout increased tumor growth in PCa xenografts in nude mice supporting its anti-oncogenic role in PCa. Knockdown of miR-214 increased the expression of its target protein, Protein Tyrosine Kinase 6 (PTK6), a kinase shown to promote oncogenic signaling and tumorigenesis in PCa. In addition, miR-214 modulated EMT as exhibited by differential regulation of E-Cadherin, N-Cadherin, and Vimentin both in vitro and in vivo. RNA-seq analysis of miR-214 knockdown cells revealed altered gene expression related to PCa tumor growth pathways, including EMT and metastasis. Collectively, our findings reveal that miR-214 is a key regulator of PCa oncogenesis and is a potential novel therapeutic target for the treatment of the disease.

Abstract((E)-2-(2-hydroxybenzylideneamino)phenolato-2,2-diphenyl-6-aza-1,3-dioxa-2-stanna- [d,h] dibenzocyclononene, [Sn(Ph 2 SB)] (compound 1, where Ph 2 SB=(E)-2-(2-hydroxybenzylideneamino)phenolato Schiff base) and two novel compounds, [[SnPh 2 (F-azoSB)] (compound 2, where F-azoSB=4-((E)-(4-fluorophenyl) diazenyl)-2-((E)-(2-hydroxyphenylimino)methyl)phenolato Schiff base), [[SnPh 2 (sulf-azoSB)]0.125CHCl 3 (compound 3, where sulfamerazineazosalSB=4-((E)-(4-hydroxy-3-((E)-(2-hydroxyphenylimino)methyl)phenyl)diazenyl)-N-(4-methylpyrimidin-2-yl) benzenesulfonamide Schiff base), and the control compound, cisplatin (compound 4) were analysed to comparatively determine their effect on cancer cell growth. Anti-cancer properties of compounds 1-4 were examined using glioblastoma (U-1242 MG), colorectal (HT-29 and HCT-116), and skin (A431) human cancer cell lines. With regards to human glioblastoma cells, compounds 1 and 3 demonstrated anti-proliferative capacity in the cell line tested. Specifically, compounds 1 and 3 inhibited cell proliferation by 50% at concentrations between 10 and 50 µM. With respect to colon cancer cell lines, the IC 50 values for compounds 1-3 ranged from 3.04 ± 0.98 to 104.51 ± 13.87 µM. In the case of HCT-116, this translates to a 3-to 73-fold inhibitory effect of compounds 1-3 over cisplatin. In all cell lines tested, the chemo-effect was more pronounced with compounds 1-3 than with the control (compound 4); demonstrating that these azo-containing Sn(IV) complexes were more potent than compound 4. The overall effect of compounds 1-3 in the induction of appotosis and the inhibition of proliferation have defined an essential role for these compounds in chemotherapy. IntroductionFrom the late 1960s until the present, there have been significant advances in both the early detection and the treatments of cancer. Despite these advances overall incidences of cancer and deaths from cancer have increased during the same period [1]. These counterintuitive increases have been the impetus for development of new drugs for cancer treatment. In this context the organometallic compounds have been widely investigated as potential anti-tumour agents. Metallocene dihalide complexes Cp 2 MX 2 (where M=titanium, vanadium, niobium, or molybdenum) were the first early transition metal complexes that were shown to have anti-tumour activity. In addition, the organometallic-DNA and organometallic-nucleic acid interactions of these compounds have also been investigated [2][3][4]. More recently, ferricenium salts, organotin, and bismuth complexes have also emerged as examples of organometallic compounds that have been found to exhibit interesting anti-tumour activity [5].The biological activity of organotin compounds has become well known due to their practical applications as fungicides, bactericides, biocides, and pesticides [3,[6][7][8]. It is now well established that organotin compounds are very important in cancer chemotherapy [9] and as potential anti-cancer agents [10][11][12][13]. This is due in part to thei...