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BACKGROUND LCL161, a Smac's small molecule mimetic, can bind to a variety of IAPs and activate Caspases. We found that, on its own, LCL161induces apoptosis of drug-resistant breast cancer cells by binding to a variety of IAPs and activating Caspases. However, when LCL161 is used in combination with Caspase Inhibitors (CI), its capacity induce apoptosis of breast cancer cells is enhanced. OBJECTIVE To carry out proteomic and bioinformatics analysis of LCL161 in combination with CI. We aim to identify the key proteins and mechanisms of breast cancer drug-resistant apoptosis, thereby aiding in the breast cancer drug resistance treatment and identification of drug targeting markers. METHODS Cell culture experiments were carried out to explore the effect of LCL161 combined with CI on proliferation of breast cancer drug-resistant cells. Proteomic analysis was carried out to determine the protein expression differences between breast cancer drug-resistant cells and LCL161 combined with CI treated cells. Bioinformatics analysis was carried out to determine its mechanism of action. Validation of proteomics results was done using Parallel reaction monitoring (PRM). RESULTS Cell culture experiments showed that LCL161 in combination with CI can significantly promote the apoptosis of breast cancer drug-resistant cells. Up-regulation of 92 proteins and down regulation of 114 proteins protein were noted, of which 4 were selected for further validation. CONCLUSION Our results show that, when LCL161 combined with CI can promote the apoptosis of drug-resistant breast cancer cells by down-regulation of RRM2, CDK4 and ITGB1 expression through Cancer pathways, p53 or PI3K-AKT signaling pathway. In addition, the expression of CDK4, RRM2 and CDC20 can be down-regulated by the nuclear receptor pathway to affect DNA transcription and replication, thereby promoting apoptosis of breast cancer drug-resistant cells. Copyright© Bentham Science Publishers; For any queries, please email at [email protected] Heat shock protein 70 (HSP70) is constitutively expressed in normal cells but aberrantly expressed in several types of tumor cells, helping their survival in the extreme conditions. Thus, specific inhibition of HSP70 in tumor cells is a promising strategy in the treatment of cancer. HSP70 has a variety of isoforms in the cellular organelles and form different functions by coordinating and cooperating with co-chaperones. Cancer cell overexpress HSPs during cell growth and proliferation and HSP network provides resistance against apoptosis. The present study aimed to evaluate quantitative changes in HSPs- and cancer-associated gene expressions and their interactions in the presence of 2-phenylethyenesulfonamide (PES) in MCF-7 cells. METHODS Antiproliferative activity of PES was evaluated using the XTT assay. Inducible HSP70 (HSP70i) levels in the PES-treated cells were determined using the ELISA kit. PCR Array was performed to assess the HSPs- and cancer-pathway focused gene expression profiling. [email protected] AND OBJECTIVE The present study was carried out to evaluate the anticancer property of an alkylamino phenol derivative -2-((3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol) (THTMP) against human breast cancer cells. The cytotoxicity of the THTMP was assessed to know its specificity towards breast cancer cells without affecting the normal cells. METHODS The THTMP was synthesized and the cytotoxicity was assessed by MTT assay, Caspases enzyme activity, DNA fragmentation and FITC/Annexin V, AO/EtBr staining, RT-PCR and QSAR. In addition, ADME analysis were executed to understand the mode of action of THTMP. RESULTS THTMP showed potential cytotoxic activity against the growth of MCF7 and SK-BR3 cells with the IC50 values of 87.92µM and 172.51µM, respectively. Interestingly, THTMP found to activate caspase 3 and caspase 9 enzymes in cancer cells, which are the key enzymes implicated in apoptosis. THTMP induced apoptosis in which 33 % of the cells entered the late apoptotic stage after 24h of treatment. Thus, the results revealed that the apoptotic response could be influenced by the association of THTMP with the Epidermal Growth Factor Receptor (EGFR) mediated inhibition of the Phosphatidylinositol 3-Kinase (PI3K)/S6K1 signaling pathway. In addition, docking was performed to study the binding mode of the THTMP, which shows better interaction with EGFR. The structural elucidation of THTMP by Quantitative Structure-Activity Relationship model (QSAR) and ADMET screening suggested, THTMP as an effective anticancer compound. CONCLUSION This work strengthens the potential of being a promising drug-like compound, THTMP, for the discovery of anticancer drug against breast cancer. Copyright© Bentham Science Publishers; For any queries, please email at [email protected] considered as inevitable changes at different levels of genome, cell, and organism. From the accumulation of DNA damages to imperfect protein homeostasis, altered cellular communication and exhaustion of stem cells, aging is a major risk factor for many prevalent diseases, such as cancer, cardiovascular disease, pulmonary disease, diabetes, and neurological disorders. The cells are dynamic systems which through a cycle of processes such as replication, growth, and death could replenish the bodies' organs and tissues, keeping an entire organism in optimal working order. In many different tissues, adult stem cells are behind of these processes, replenishing dying cells to maintain normal tissue function and regenerating injured tissues. Therefore, adult stem cells play a vital role in preventing the aging of organs and tissues, and can delay aging. However, during aging these cells also undergo some detrimental changes such as alterations in the microenvironment, decline in the regenerative capacity, and loss of function. This review aims to discuss age-related changes of stem cells in different tissues and cells including skin, muscles, brain, heart, hair follicles, liver, and lung. Selleck Valproic acid Copyright© Bentham Science Publishers; For any queries, please email at [email protected].
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