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11, 25 dihydroxy vitamin D3, an active metabolite of vitamin­D3 has been reported to inhibit the growth of number neoplasms such as prostate, breast, colorectal, leukemia and skin cancers. Valproic acid, as a potent histone deacetylase inhibitor, also plays an important role in inhibition of proliferation of tumor cells. However, there are no reports so far on the cooperation between valproic acid and vitamin­ D3 for anti-leukemic effect. The goal of the present research was to evaluate whether low doses of vitamin D3 potentiate the toxicity of valproic acid and whether this toxic action is mediated via apoptotic mechanisms. In this study HL-60 cells were treated either with different concentrations of valproic acid and vitamin­ D3 alone and in combination with each other for 24 hours. Cell survival was determined by MTT assay and then Hoechst staining was used to determine the type of death cell. This present study indicates that vitamin ­D3 potentiates the antitumor effects of valproic acid. Also, the results of staining cells showed that valproic acid and vitamin ­D3 induced apoptosis in HL-60 cells. In total, the new combination of valproic acid and vitamin D3 showed synergistic anti-proliferative effect and induced apoptosis on HL-60 cancer cells.
                                                                       

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The XIAP protein is a member of apoptosis proteins family. The XIAP protein plays a central role in the inhibition of apoptosis and consists of three Baculoviral IAP Repeat domains. The BIR3 domain binds directly to the N-terminal of caspase-9 and therefore it inhibits apoptosis. N-terminal tetrapeptide region of SMAC protein can bind to BIR3, inhibit it and subsequently induce apoptosis. In this study, fifteen tetrapeptides were docked into the BIR3 domain and then 10 ns molecular dynamics simulations were performed on each of the BIR3-peptide complex obtained from docking. MM/PBSA method was subsequently used to calculate the binding free energy of peptides to BIR3. The results of MM/PBSA method were in good coordination with docking and existing expermental results.  The results showed the most potent peptides with the lowest binding free energy for binding to BIR3 included ATPF, AKPW and ARPF peptides. Also, investigation of bonds between these peptides and BIR3 domain in the final structure of complexes showed that Leu 307, Thr 308, Glu 314 and Tyr 324 of the BIR3 domain were essential for binding of peptides. Energy decomposition results for binding these peptides to the BIR3 domain during MD simulation was inconsistent with previous results and approved the roles of the same residues. The higher affinity of these peptides relative to native peptide (AVPI) and comparing them with other peptides revealed that the existence of positive charge in the second position and the existence of the aromatic group in the fourth position led to more binding affinity.

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Nowadays natural compounds are increasingly used in various fields since they cause fewer adverse side effects than their chemical counterparts. In addition, preparation and production of natural compounds are comparatively simple. The present study aimed to evaluate the anti-cancer effects of brittle star methanol extract on MCF-7 cells. Anti-cancer effects of brittle star methanol extract were examined on the MCF-7 cell line. Moreover, the toxicity of this compound was assessed using cell apoptosis methods, ethidium bromide/acridine orange (EB/AO) staining and Annexin V Apoptosis Detection Kit. According to the MTT assay, the methanolic extract of brittle star could prevent proliferation in a time- and dose-dependent manner. The calculated inhibitory concentration that decreased the cell-viability by half (IC₅₀) was estimated at 150 µg/ml. On the other hand, results of EB/AO staining were indicative of increased apoptotic cells in the treatment group. In addition, results of Annexin V/PI protocol demonstrated a significant enhancement in the percentage of late apoptotic cells (29.02%) in the treatment groups (150 µg/ml) and the percentage of necrotic cells were 2.77% for a period of 24 hours. According to the results, the methanolic extract of Persian Gulf brittle star induced apoptosis in the MCF-7 cell line. These effects could be attributed to the presence of certain active biological compounds, such as Saponins, Naphthoquinones and Carotenoids. Furthermore, our findings suggested that brittle star might have beneficial effects on cancer management. Therefore, this natural marine compound could be used as a complementary element in the prevention and treatment of cancer.

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In this study, the cytotoxic effects of aqueous and ethanolic extracts of Sedum album L. on human stomach cancer cell line (AGS) and breast cancer cell line (MCF-7) were evaluated by MTT, BrdU and TUNEL assays. The results demonstrated that both extracts had antiproliferative and apoptotic effects in a dose-dependent manner. The MTT assay data revealed that the AGS cell underwent more cytotoxicity in comparison with the MCF-7 cell. It also revealed that ethanolic extract was more potent than aqueous extract. The BrdU assay results showed that the proliferation of AGS and MCF-7 cells was reduced to 50% and 43%, respectively, at the highest concentration of the aqueous extract. In addition, the ethanolic extract reduced the proliferation of AGS and MCF-7 cells to 75% and 60%, respectively. The AGS and MCF-7 cells underwent 52% and 12% apoptotic death upon treatment by the ethanolic extract as TUNEL assay showed. The aqueous extract induced 28% and 25% apoptosis in the AGS and MCF-7 cells, respectively. Both inhibition of proliferation and induction of apoptosis are desirable strategies for cancer treatment among researchers. Identification of S. album compounds and analyzing their effects in animal model of cancer can help us with understanding its anti-cancer properties.
 

 

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Superparamagnetic iron oxide nanoparticles (SPIONs) have made extensive advances in nanotechnology. The unique properties of these particles have expanded their application in various fields, including medicine. One of these applications is non-invasive analysis for cell tracking. However, the possibility of toxicity in cells is reported by these nanoparticles. Due to the fact that cellular damage caused by iron oxide nanoparticles is concentration-dependent, the determination of the appropriate  concentration of iron oxide nanoparticles is very important to prevent cell damage or cell death due to apoptosis. The aim of this study was to find a concentration of SPIONs which does not result in apoptosis. Therefore, the effects of different concentrations of iron oxide nanoparticles on cell survival were investigated, and the their effects on increased gene expression involved in apoptosis (p53) in human amniotic membrane derived mesenchymal stem cells (hAMSCs) were evaluated. First, stem cells were extracted from human amniotic membrane tissue and cultured. To demonstrate the multipotent characteristic of hAMSCs, these cells were differentiated into adipose, bone, and chondrocyte cell lines. Then, the viability of the cells treated with different concentrations of iron oxide nanoparticles (200, 150, 100, 50, 0 μg / ml) over a period of 24 and 48 hours was evaluated by MTT method. The effect of the concentrations of 0, 100,150 and 200 μg / ml of nanoparticles after 24 hours in hAMSCs was investigated for the expression of p53 gene by Real-Time PCR. hAMSCs were spindle-shaped in a two-dimensional culture. Flow cytometry examination of surface markers revealed that these cells were able to express CD 29, CD90 and CD105 but they were unable to express CD34 and CD45. The results of the multi-potency assay of hAMSCs showed that these cells were capable of being differentiated into adipocyte, bone and chondrocyte cell lines. Iron oxide nanoparticles had no significant effect on cell survival at the concentrations of 50 and 100 μg / ml in 24 hours. However, cell viability decreased significantly after the concentration of 150 μg / ml (42 ± 1.4%, p<0. 001. The results of Real-Time PCR  analysis showed that the expression of p53 gene significantly increased at concentrations of 150 (2.4±0.1, P < 0. 001) and 200 μg / ml (4.1 ± 0.11, P < 0. 001). According to the results, the nanoparticles used in this study were appropriate at concentrations ≥ 100 μg / ml for cell tracking.

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Lung carcinoma is the second most common type of cancer. Inefficiency of the current treatments and the undesirable side effects of chemotherapy drugs made the know-how of the treatment important. The purpose of this study is to investigate the synergic effect of curcumin and Cisplatin in comparison with the sole application of each treatment on Calu-6 cell line, an epithelial cell line of human lung carcinoma, and the expression of Cdc42 gene. The viability of Calu-6 was examined after 24- or 48-hour treatment with doses of 0.5 to 8 µg/ml of curcumin, 0.1 to 50 µg/ml of cisplatin and combined doses of curcumin and Cisplatin by MTT assay. To measure apoptosis and the expression of Cdc42 gene, flow cytometry and Real-Time PCR were utilized. Decrease of cell viability and induction of cell death were observed in the cells treated with 0.67 µg/ml of curcumin and 1.7 µg/ml of cisplatin (the lowest effective dose) and the combined treatment with the same doses of each drug after 24-hour treatments. The maximum rates of early and late apoptosis were related to treatment with curcumin and the combined treatment. The gene expression analysis results indicated that both Curcumin and Cisplatin decrease the expression of Cdc42 gene, moreover, their co-administration showed synergic effects. Therefore, Curcumin could be an appropriate option for complementary administration with other chemotherapy agents in order to reduce their efficient dose, and to reduce their side effects.
 
 

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The aim of this study was to investigate the effective genes on apoptosis (BAX and Bcl₂) in liver and intestinal cells of broiler chickens fed silver nanoparticles coated on clinoptilolite under acute heat stress induction. 450 d old broiler chicks (Cobb 500) were used in five treatments and six repetitions, and 15 pieces were used in each experimental unit in the form of a completely random design. Experimental diets were: 1) control or basal diet 2) basal diet supplemented by 1% clinoptilolite 3) basal diet supplemented by 1% clinoptilolite coated with 0.5% nanosilver 4) basal diet supplemented by 0.15% organic acid and  5) basal diet supplemented by 1% clinoptilolite coated with 0.5% nanosilver and 0.15% organic acid. Silver nanoparticles coated on clinoptilolite were investigated using XRF and FTIR techniques. In order to induce heat stress, the birds were affected by heat stress for one week in the last week of the breeding period, and on the last day of the stress, liver and intestine samples were obtained to check gene expression. The results of this experiment show that the treatments of clinoptilolite and silver nanoparticles coated on clinoptilolite have an increasing effect on the expression of Bcl₂ and Bax, while this effect was not seen in the organic acid treatment. In conclusion, it could be said that if silver nanoparticles are used in feeding livestock and poultry, it is better to use organic acid supplements to reduce the side effects of silver nanoparticles.