Cancer was ranked as the second leading cause of death, and colon cancer has been reported as the third most frequent cancer worldwide. Chemotherapeutic drugs act on normal and cancerous cells similarly; therefore, they have various adverse side effects. Nanoparticles were identified to have a controlled effect on different cancer cell lines. The present study is aimed at studying biosynthesis silver nanoparticles by using aqueous Olea chrysophylla and Lavandula dentata leaf extracts, separately, and evaluating their anticancer potential. Silver nanoparticles were characterized by using SEM, XRD, FTIR, zeta potential, and size distribution mean, and their antiproliferative and apoptotic potentials were evaluated on HCT116 cells. Results show the formation of silver nanoparticles Olea-AgNPs and Lav-AgNPs due to the change of color to dark brown, and characterization revealed their crystalline shape with a mean size of 284.5 nm for Lav-AgNPs and 328.6 nm for Olea-AgNPs. Lav-AgNPs shows more stability than Olea-AgNPs due to its higher negative zeta potential (-14.3 mV) than nanoparticles biosynthesized from Olea leaves (-0.877 mV). Conversely, Lav-AgNPs shows more effective antiproliferative potential on HCT116 with (IC50 = 59.79 μg/ml) than Olea-AgNPs (IC50 = 99.35 μg/ml). However, Olea-AgNPs significantly increased the late stage of apoptotic and necrotic cells in comparison to Lav-AgNPs-treated cells in flow cytometry assay. Silver nanoparticles biosynthesized from Olea and lavender show anticancer potential with a more effective potential reported compared to Lav-AgNPs.
17 July 2019 in Molecular Genetics & Genomic Medicine
Background: BRCA1/2 pathogenic variants have become associated with familial breast and ovarian cancers, and hereditary cancer‐predisposition syndrome. With advances in molecular biology, BRCA profiling facilitates early diagnosis and the implementation of preventive and therapeutic strategies. The genes exhibit variable prevalence among different individuals and moderate interpretation complexity. BRCA deficiency is instrumental in cancer development, affects therapeutic options and is instrumental in drug resistance. In addition, BRCA1/2 profile is diverse across different groups and has been associated with the “founder effect” in certain populations.Methods: In this review, we aim to detail the spectrum of BRCA1/2 variants and their associated risk estimates.Results: The relationship between BRCA1/2 and hereditary and familial cancers is indisputable, yet BRCA screening methods are beset with limitations and lack clinical confidence.Conclusion: This review emphasizes the importance of screening BRCA genetics, in addition to their clinical utility. Furthermore, founder variants are anticipated in the Saudi population.
The full-length BRCA1-associated RING domain 1 (BARD1) gene encodes a 777-aa protein. BARD1 displays a dual role in cancer development and progression as it acts as a tumor suppressor and an oncogene. Structurally, BARD1 has homologous domains to BRCA1 that aid their heterodimer interaction to inhibit the progression of different cancers such as breast and ovarian cancers following the BRCA1-dependant pathway. In addition, BARD1 was shown to be involved in other pathways that are involved in tumor suppression (BRCA1-independent pathway) such as the TP53-dependent apoptotic signaling pathway. However, there are abundant BARD1 isoforms exist that are different from the full-length BARD1 due to nonsense and frameshift mutations, or deletions were found to be associated with susceptibility to various cancers including neuroblastoma, lung, breast, and cervical cancers. This article reviews the spectrum of BARD1 full-length genes and its different isoforms and their anticipated associated risk. Additionally, the study also highlights the role of BARD1 as an oncogene in breast cancer patients and its potential uses as a prognostic/diagnostic biomarker and as a therapeutic target for cancer susceptibility testing and treatment.
Human dental pulp cells (DPCs), which are known to contain a subset of stem cells capable of reforming a dentin and pulp-like complex upon in vivo transplantation, were isolated from third molars of three healthy donors and differentiated to a matrix mineralisation phenotype using by culture in dexamethasone and l-ascorbic acid. qRT-PCR analysis of insulin-like growth factor ( IGF) axis gene expression indicated that all genes, except insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein-1 ( IGFBP-1), were expressed in DPCs. During differentiation upregulation of insulin-like growth factor binding protein-2 (IGFBP-2) and downregulation of insulin-like growth factor binding protein-3 (IGFBP-3) expression was observed. Changes in IGFBP-2 and IGFBP-3 mRNA expression were confirmed at the protein level by ELISA of DPC conditioned medium functional analysis indicated that IGF1 stimulated the differentiation of DPCs and that the activity of the growth factor was enhanced by pre-complexation with IGFBP-2 but inhibited by pre-complexation with IGFBP-3. Therefore changes in IGFBP-2 and -3 expression during differentiation form part of a co-ordinated functional response to enhance the pro-differentiative action of IGF1 and represent a novel mechanism for the regulation of DPC differentiation.
The use of insects as a feasible and useful natural product resource is a novel and promising option in alternative medicine. Several components from insects and their larvae have been found to inhibit molecular pathways in different stages of cancer. This study aimed to analyze the effect of aqueous and alcoholic extracts of Vespa orientalis larvae on breast cancer MCF7 cells and investigate the underlying mechanisms. Our results showed that individual treatment with 5% aqueous or alcoholic larval extract inhibited MCF7 proliferation but had no cytotoxic effect on normal Vero cells. The anticancer effect was mediated through (1) induction of apoptosis, as indicated by increased expression of apoptotic genes (Bax, caspase3, and p53) and decreased expression of the anti-apoptotic gene Bcl2; (2) suppression of intracellular reactive oxygen species; (3) elevation of antioxidant enzymes (CAT, SOD, and GPx) and upregulation of the antioxidant regulator Nrf2 and its downstream target HO-1; (4) inhibition of migration as revealed by in vitro wound healing assay and downregulation of the migration-related gene MMP9 and upregulation of the anti-migratory gene TIMP1; and (5) downregulation of inflammation-related genes (NFκB and IL8). The aqueous extract exhibited the best anticancer effect with higher antioxidant activities but lower anti-inflammatory properties than the alcoholic extract. HPLC analysis revealed the presence of several flavonoids and phenolic compounds with highest concentrations for resveratrol and naringenin in aqueous extract and rosmarinic acid in alcoholic extract. This is the first report to explain the intracellular pathway by which flavonoids and phenolic compounds-rich extracts of Vespa orientalis larvae could induce MCF7 cell viability loss through the initiation of apoptosis, activation of antioxidants, and inhibition of migration and inflammation. Therefore, these extracts could be used as adjuvants for anticancer drugs and as antioxidant and anti-inflammatory agents.