No abstract

Breast cancer with more than 1.7 million diagnoses per year has been known as one of the most prevalent cancers among women worldwide. Despite the availability of advanced treatment options, cancer progression and metastasis is observed in 20% of patients. Human epidermal growth factor receptor-2 (HER-2) is considered as an important prognostic and diagnostic tumor marker for breast cancer. While HER-2 is expressed on the surface of normal cells, its overexpression occurs in 20-25% on breast cancer tumor cells. This type of tumor which is referred to as HER-2+ is the most aggressive type of breast cancer and shows more resistance to radiotherapy. Single-chain fragment antibodies (ScFvs) offer several advantages in comparison to conventional whole antibodies due to their small size. Particularly, ScFv fragments show improved diffusion and solid tumor penetration. In this study, a human ScFv antibody library was used to isolate anti-HER-2 ScFv antibodies through cell panning and mix antigen-cell panning strategies. Analysis of the binding activity and specificity of isolated ScFv antibodies against HER-2-expressing cell lines and recombinant HER-2 antigen indicated the higher efficiency of the cell panning strategy in isolation of ScFv antibody fragments.

Prostate cancer (PCa) was known as the second most common cancer in men. Although there were several approaches to treat this disease, the cost and side effects of some approaches have encountered the patients with challenges. Therefore, the design of new therapy methods could be useful in the management of this disease. For this purpose, the synergic effect of Epigallocatechin gallate (EGCG) and conditioned medium derived from Wharton's jelly mesenchymal stem cells (WJ-MSCs) were studied on prostate cancer LNCaP cells. In this study, LNCaP cells were treated with different concentrations of EGCG and conditioned medium derived from WJ-MSCs (WJCM). The viability of treated cells was determined by using cell proliferation assay. Then, the expression of androgen receptor (AR and PSA) and apoptotic (BAX, CASP3 and CASP7) pathway genes were defined by Real time PCR. The analysis of the data indicated that the treatment with 400µM EGCG in combination with 50% WJCM (0% FBS) for 72 hours decreased expression of AR and PSA genes as well as the enhanced expression of BAX, CASP3 and CASP7 genes in the LNCaP cells (p<0.05). The obtained results suggested that the combination therapy of EGCG and WJCM had an anticancer effect on LNCaP cells through activation of apoptotic pathway and suppression of androgen receptor pathway.

Imidazo[1,2-a]pyridine derivatives with diverse pharmacological properties and Curcumin, as a potential natural anti-inflammatory compound, are promising compounds for cancer treatment. This study aimed to synthesize a novel imidazo[1,2-a]pyridine derivative, (MIA), and evaluate its anti-inflammatory activity and effects on nuclear factor-kB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways, and their target genes, alone and in combination with curcumin, in MDA-MB-231 and SKOV3 cell lines. Methods: We evaluated the interaction between imidazo[1,2-a]pyridine ligand, curcumin, and NF-κB p50 protein using the molecular docking studies. MTT assay was used to investigate the impacts of compounds on cell viability. To evaluate the NF-κB DNA binding activity and the level of inflammatory cytokines in response to the compounds, ELISA-based methods were performed. In addition, quantitative polymerase chain reaction (qPCR) and western blotting were carried out to analyze the expression of genes and investigate NF-κB and STAT3 signaling pathways. Results: Molecular docking studies showed that MIA docked into the NF-κB p50 subunit, and curcumin augmented its binding. The MTT assay results indicated that MIA and its combination with curcumin reduced cell viability. According to the results of the ELISA-based methods, MIA lowered the levels of inflammatory cytokines and suppressed NF-κB activity. In addition, real-time PCR and Griess test results showed that the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) genes, and nitrite production were reduced by MIA. Furthermore, the western blotting analysis demonstrated that MIA increased the expression of inhibitory κB (IκBα) and B-cell lymphoma 2 (Bcl-2)-associated X proteins (BAX), and suppressed the STAT3 phosphorylation, and Bcl-2 expression. Our findings revealed that curcumin had a potentiating role and enhanced all the anti-inflammatory effects of MIA. Conclusion: This study indicated that the anti-inflammatory activity of MIA is exerted by suppressing the NF-κB and STAT3 signaling pathways in MDA-MB-231 and SKOV3 cancer cell lines.

Prostate cancer (PCa) was known as the second most common cancer in men. Although there were several approaches to treat this disease, the cost and side effects of some approaches have encountered the patients with challenges. Therefore, the design of new therapy methods could be useful in the management of this disease. For this purpose, the synergic effect of Epigallocatechin gallate (EGCG) and conditioned medium derived from Wharton's jelly mesenchymal stem cells (WJ-MSCs) were studied on prostate cancer LNCaP cells. In this study, LNCaP cells were treated with different concentrations of EGCG and conditioned medium derived from WJ-MSCs (WJCM). The viability of treated cells was determined by using MTT assay. Then, the expression of androgen receptor (AR and PSA) and apoptotic (BAX, CASP3 and CASP7) pathway genes were defined by Real time PCR. The analysis of the data indicated that the treatment with 400µM EGCG in combination with 50% WJCM (0% FBS) for 72 hours decreased expression of AR and PSA genes as well as the enhanced expression of BAX, CASP3 and CASP7 genes in the LNCaP cells (p < 0.05). The obtained results suggested that the combination therapy of EGCG and WJCM had an anticancer effect on LNCaP cells through activation of apoptotic pathway and suppression of androgen receptor pathway.