Bioactive compounds were extracted from a locally available brittle star; Ophiocoma dentata, collected from the Red Sea, Egypt. Two new sesquiterpenoids; 8, 11-epoxy-9(15)-himachaladiene-4-ol (O8-ophiocomane) and, 11-epoxy-9(15)-himachaladiene-4-ol (O7-ophiocomane) were isolated and characterized using appropriate techniques. Structure elucidation was estimated via 1D NMR, 2D NMR, FT-IR and mass spectroscopy analyses. The isolated compounds were tested for cytotoxic, antibacterial and antifungal activities. Pure compounds showed a dose dependent reduction in MCF-7 cells viability with LC50 of 103.5 and 59.5 μg/ml for compounds 1 and 2 respectively compared to the chemotherapeutic drug cisplatin (47.4 µg/ml). In vivo experiments showed that O. dentate extract significantly reduced tumor progression and improved hematological parameters and liver functions of tumor-bearing mice when administered either before or after tumor cells’ injection. The most remarkable antimicrobial effects of O. dentate crude extract were against Staphylococcus aureus, Vibrio damsela and Pseudomonasaeruginosa while the pure compounds showed activity against P. aeruginosa alone. Neither the crude extract nor the pure compounds have shown activity against Aeromonas hydrophila. These results indicates that O. dentata extract and newly isolated compounds have shown a promising cytotoxic, antiproliferative and antimicrobial activities that might be useful for pharmaceutical applications.

Targeting the thioredoxin/thioredoxin reductase (Trx/TrxR) system is a promising strategy to overcome cancer resistance to conventional therapy. The present study investigated the effect of curcumin on the Trx/TrxR system either alone or in combination with chemotherapy, or radiotherapy in human MCF-7 breast cancer cells seeded in 2 and 3D culture systems. Cell viability, thioredoxin reductase 1 (TrxR1) activity, and the genetic expression of Trx, TrxR1, Bcl2 and BAX genes were studied. The findings showed that the mode of culture significantly affected the response of cancer cells to different treatment modalities, as well as their gene expression patterns. Curcumin treatment resulted in a reduction of breast cancer cell proliferation and induction of apoptosis, an effect that may be mediated by manipulating Trx system components, mainly Trx expression, and to a lesser extent TrxR1 expression and concentration. Furthermore, curcumin increased the sensitivity of breast cancer cells to chemotherapy and radiotherapy by reducing Trx and TrxR1 expression levels. Thus, curcumin may have a potential role as a dose-modifying agent that can be used either to sensitize resistant cells to therapy or to reduce the dose of these therapeutic agents.

Background: hTERT is a key player in telomere biology and its activity is directly related to cell senescence and development of many health-related problems including cancer. Although previous studies investigated this association, the results greatly vary among populations. This study aimed to investigate the association of hTERT gene SNPs and the risk of breast cancer (BC) in Egyptian females and their impact on telomere length (TL). Methods: 218 BC patients and 178 age-matched healthy females were genotyped for hTERT variants rs2736098G > A, rs2735940C > T using PCR-RFLP and for MNS16A tandem repeat using PCR to determine their association with breast cancer risk. Telomere length was measured using qPCR. Results: hTERT rs2736098G > A results indicated that both AG and GG genotypes and G allele were associated with an increased risk of BC. The rs2735940 TT genotype was significantly associated with BC risk, however, the MNS16A tandem repeat region polymorphism didn't show any correlation with the risk of developing BC. TL showed a significant reduction in BC patients with age < 40 years compared with controls. However, it didn't show a significant difference above the age of 40 years. Conclusions: hTERT rs2736098 and rs27365940, not MNS16A may be associated with an increased risk of developing BC in Egyptian females. Also, telomere length can be a promising screening marker of BC especially in young population.

Triple negative is a subtype of breast cancer characterized by lack of expression of hormone receptors (ER, PR and Her2/neu). Due to the limited treatment options, the search for novel treatment targets continues. The aim of this study was to assess the differential expression of miR-206, VEGF and KRAS in TNBC and non-TNBC tissues and cell lines and to evaluate the modulatory effect of miR-206 on the key oncogenic targets VEGF and KRAS. The expression of miR-206, VEGF and KRAS was quantified using real time PCR in both paraffin embedded breast cancer and adjacent tissues as well as in MDA-MB-231 and MCF-7 cell lines. Cell lines were transfected with different concentrations of miR-206 mimic and their viability were assessed using MTT assay. Our results indicated that miR-206 was significantly downregulated in cancerous compared to non-cancerous tissues with a more pronounced downregulation in TNBC than non-TNBC tissues. VEGF and KRAS were significantly upregulated in TNBC compared to non-TNBC and their expression was negatively correlated to miR-206 expression. Transfection of TNBC and non-TNBC cell lines with miR-206 mimic resulted in a dose dependent reduction in cell viability as well as a significant reduction in VEGF and KRAS expression. In conclusion, based on our combined human tissues and cell line-based investigations we can suggest that VEGF and KRAS may be potential targets for miR-206-mediated regulation and that their targeting by miR-206 can be a highly efficient therapeutic strategy in TNBC.

Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a key player in the extrinsic pathway of apoptosis; it selectively damages cancer cells through binding to its surface receptors, however, cancers can escape this pathway through expression of dysfunctional decoy receptors. Purpose: The present study directed mainly to elucidate the serum TRAIL levels in breast cancer patients and to explore the variation in gene expression of TRAIL death and decoy receptors in breast cancer tissues, and to explore their role as prognostic markers in breast cancer as well as to detect their correlation with Patients' Clinical Characteristics. Subjects and Methods: TRAIL levels were assayed in the sera of 124 breast cancer patients and 150 healthy females. Moreover, the expression of TRAIL death and decoy receptors was determined in both malignant and adjacent normal breast tissues collected from patients. ER, PR and Her-2 expression in breast cancer tissue were performed using immunohistochemical method. Apoptotic index (AI) was analyzed using H&E stain under light microscopy. Results: Serum levels of TRAIL in breast cancer patients were significantly lower than controls (P < 0.001), additionally, the expression of DR4, DR5 and DcR1 were significantly up-regulated (p < 0.001, p < 0.001, p = 0.039, respectively), however, no significant difference was found in the expression of DcR2 in breast cancer tissues as compared to the corresponding normal tissues. Moreover, the apoptotic index in breast cancer tissues was significantly higher than the corresponding normal tissues. On the other side, decreased Serum TRAIL levels and increased DcR1 expression were associated with decreased overall patients' survival. Conclusions: The expression of both DR4 and DR5 is required for TRAILinduced apoptosis in breast cancer tissues; in addition, serum TRAIL and pro-How to cite this paper: Ibrahim