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A novel series of (Z)-3,5-disubstituted thiazolidine-2,4-diones 4-16 has been designed and synthesized. Preliminary screening of these compounds for their anti-breast cancer activity revealed that compounds 5, 7, and 9 possess the highest anti-cancer activities. The anti-tumor effects of compounds 5, 7, and 9 were evaluated against human breast cancer cell lines (MCF-7 and MDA-MB-231) and human breast cancer cells. They were also evaluated against normal non-cancerous breast cells, isolated from the same patients, to conclude about their use in a potential targeted therapy. Using MTT uptake method, these three compounds 5, 7, and 9 blunt the proliferation of these cancer cells in a dose-dependent manner with an IC50 of 1.27, 1.50 and 1.31 µM respectively. Interestingly, using flow cytometry analysis these three compounds significantly mediated apoptosis of human breast cancer cells without affecting the survival of normal non-cancerous breast cells that were isolated from the same patients. Mechanistically, these compounds blunt the proliferation of MCF-7 breast cancer cells by robustly decreasing the phosphorylation of AKT, mTOR and the expression of VEGF and HIF-1α. Most importantly, compounds 5, 7, and 9 without affecting the phosphorylation and expression of these crucial cellular factors in normal non-cancerous breast cells that were isolated from the same patients. Additionally, using Western blot analysis the three compounds significantly (P < 0.05) decreased the expression of the anti-apoptotic Bcl-2 members (Bcl-2, Bcl-XL and Mcl-1) and increased the expression of the pro-apoptotic Bcl-2 members (Bak, Bax and Bim) in MCF-7, MDA-MB-231 and human breast cancer cells making these breast cancer cells susceptible for apoptosis induction. Taken together, these data provide great evidences for the inhibitory activity of these compounds against breast cancer cells without affecting the normal breast cells.

A novel series of (Z)-3,5-disubstituted thiazolidine-2,4-diones 4-16 has been designed and synthesized. Preliminary screening of these compounds for their anti-breast cancer activity revealed that compounds 5, 7, and 9 possess the highest anti-cancer activities. The anti-tumor effects of compounds 5, 7, and 9 were evaluated against human breast cancer cell lines (MCF-7 and MDA-MB-231) and human breast cancer cells. They were also evaluated against normal non-cancerous breast cells, isolated from the same patients, to conclude about their use in a potential targeted therapy. Using MTT uptake method, these three compounds 5, 7, and 9 blunt the proliferation of these cancer cells in a dose-dependent manner with an IC50 of 1.27, 1.50 and 1.31 µM respectively. Interestingly, using flow cytometry analysis these three compounds significantly mediated apoptosis of human breast cancer cells without affecting the survival of normal non-cancerous breast cells that were isolated from the same patients. Mechanistically, these compounds blunt the proliferation of MCF-7 breast cancer cells by robustly decreasing the phosphorylation of AKT, mTOR and the expression of VEGF and HIF-1α. Most importantly, compounds 5, 7, and 9 without affecting the phosphorylation and expression of these crucial cellular factors in normal non-cancerous breast cells that were isolated from the same patients. Additionally, using Western blot analysis the three compounds significantly (P < 0.05) decreased the expression of the anti-apoptotic Bcl-2 members (Bcl-2, Bcl-XL and Mcl-1) and increased the expression of the pro-apoptotic Bcl-2 members (Bak, Bax and Bim) in MCF-7, MDA-MB-231 and human breast cancer cells making these breast cancer cells susceptible for apoptosis induction. Taken together, these data provide great evidences for the inhibitory activity of these compounds against breast cancer cells without affecting the normal breast cells.

A novel series of (Z)-3,5-disubstituted thiazolidine-2,4-diones 4-16 has been designed and synthesized. Preliminary screening of these compounds for their anti-breast cancer activity revealed that compounds 5, 7, and 9 possess the highest anti-cancer activities. The anti-tumor effects of compounds 5, 7, and 9 were evaluated against human breast cancer cell lines (MCF-7 and MDA-MB-231) and human breast cancer cells. They were also evaluated against normal non-cancerous breast cells, isolated from the same patients, to conclude about their use in a potential targeted therapy. Using MTT uptake method, these three compounds 5, 7, and 9 blunt the proliferation of these cancer cells in a dose-dependent manner with an IC50 of 1.27, 1.50 and 1.31 µM respectively. Interestingly, using flow cytometry analysis these three compounds significantly mediated apoptosis of human breast cancer cells without affecting the survival of normal non-cancerous breast cells that were isolated from the same patients. Mechanistically, these compounds blunt the proliferation of MCF-7 breast cancer cells by robustly decreasing the phosphorylation of AKT, mTOR and the expression of VEGF and HIF-1α. Most importantly, compounds 5, 7, and 9 without affecting the phosphorylation and expression of these crucial cellular factors in normal non-cancerous breast cells that were isolated from the same patients. Additionally, using Western blot analysis the three compounds significantly (P < 0.05) decreased the expression of the anti-apoptotic Bcl-2 members (Bcl-2, Bcl-XL and Mcl-1) and increased the expression of the pro-apoptotic Bcl-2 members (Bak, Bax and Bim) in MCF-7, MDA-MB-231 and human breast cancer cells making these breast cancer cells susceptible for apoptosis induction. Taken together, these data provide great evidences for the inhibitory activity of these compounds against breast cancer cells without affecting the normal breast cells.

Exposure to ionizing radiation emitted from natural sources induces many health hazards. The response to ionizing radiation involves a number of mediators including inflammatory cytokines and free radicals which mediate immunosuppression. The present study aimed to monitor the impact of exposure to natural radioactive rocks from the Egyptian eastern desert on the primary immune organs. Therefore, three experimental groups (15 rats per group) were used: group I included the control non-irradiated rats; group II included rats that were exposed for 28 consecutive days to natural radioactive rocks from the Egyptian eastern desert (IR/R group); and group III (positive control group) included rats that were exposed to high dose of γ-rays (4 Gy/14 days for 28 days) (IR/γR group). We found that rats of both the IR/R and IR/γR groups exhibited pathological alterations in the architecture of the primary immune organs (bone marrow and thymus). Additionally, the levels of C-reactive protein (CRP), proinflammatory cytokines (IL-1β, IL-6 and TNF-α), and reactive oxygen species (ROS) were significantly increased in the IR/R and IR/γR groups compared to the control group. Furthermore, rats from the IR/R and IR/γR groups exhibited significant increase in the activity of caspase-3 and caspase-9 and subsequently exhibited a significant increase in the apoptosis of PBMCs compared with the control group. Most importantly, apoptosis induction in the PBMCs was associated with increased expression of cyclin B1 and decreased expression of cyclin D1 and survivin compared with the control non-irradiated group. Taken together, our data demonstrated that consecutive exposure to natural radioactive rocks from the Egyptian eastern desert could dampen the immune response through damaging the architectures of the immune system and mediating serious health problems to the population inhabiting this region.

Exposure to ionizing radiation emitted from natural sources induces many health hazards. The response to ionizing radiation involves a number of mediators including inflammatory cytokines and free radicals which mediate immunosuppression. The present study aimed to monitor the impact of exposure to natural radioactive rocks from the Egyptian eastern desert on the primary immune organs. Therefore, three experimental groups (15 rats per group) were used: group I included the control non-irradiated rats; group II included rats that were exposed for 28 consecutive days to natural radioactive rocks from the Egyptian eastern desert (IR/R group); and group III (positive control group) included rats that were exposed to high dose of γ-rays (4 Gy/14 days for 28 days) (IR/γR group). We found that rats of both the IR/R and IR/γR groups exhibited pathological alterations in the architecture of the primary immune organs (bone marrow and thymus). Additionally, the levels of C-reactive protein (CRP), proinflammatory cytokines (IL-1β, IL-6 and TNF-α), and reactive oxygen species (ROS) were significantly increased in the IR/R and IR/γR groups compared to the control group. Furthermore, rats from the IR/R and IR/γR groups exhibited significant increase in the activity of caspase-3 and caspase-9 and subsequently exhibited a significant increase in the apoptosis of PBMCs compared with the control group. Most importantly, apoptosis induction in the PBMCs was associated with increased expression of cyclin B1 and decreased expression of cyclin D1 and survivin compared with the control non-irradiated group. Taken together, our data demonstrated that consecutive exposure to natural radioactive rocks from the Egyptian eastern desert could dampen the immune response through damaging the architectures of the immune system and mediating serious health problems to the population inhabiting this region.

Exposure to ionizing radiation emitted from natural sources induces many health hazards. The response to ionizing radiation involves a number of mediators including inflammatory cytokines and free radicals which mediate immunosuppression. The present study aimed to monitor the impact of exposure to natural radioactive rocks from the Egyptian eastern desert on the primary immune organs. Therefore, three experimental groups (15 rats per group) were used: group I included the control non-irradiated rats; group II included rats that were exposed for 28 consecutive days to natural radioactive rocks from the Egyptian eastern desert (IR/R group); and group III (positive control group) included rats that were exposed to high dose of γ-rays (4 Gy/14 days for 28 days) (IR/γR group). We found that rats of both the IR/R and IR/γR groups exhibited pathological alterations in the architecture of the primary immune organs (bone marrow and thymus). Additionally, the levels of C-reactive protein (CRP), proinflammatory cytokines (IL-1β, IL-6 and TNF-α), and reactive oxygen species (ROS) were significantly increased in the IR/R and IR/γR groups compared to the control group. Furthermore, rats from the IR/R and IR/γR groups exhibited significant increase in the activity of caspase-3 and caspase-9 and subsequently exhibited a significant increase in the apoptosis of PBMCs compared with the control group. Most importantly, apoptosis induction in the PBMCs was associated with increased expression of cyclin B1 and decreased expression of cyclin D1 and survivin compared with the control non-irradiated group. Taken together, our data demonstrated that consecutive exposure to natural radioactive rocks from the Egyptian eastern desert could dampen the immune response through damaging the architectures of the immune system and mediating serious health problems to the population inhabiting this region.

Exposure to ionizing radiation emitted from natural sources induces many health hazards. The response to ionizing radiation involves a number of mediators including inflammatory cytokines and free radicals which mediate immunosuppression. The present study aimed to monitor the impact of exposure to natural radioactive rocks from the Egyptian eastern desert on the primary immune organs. Therefore, three experimental groups (15 rats per group) were used: group I included the control non-irradiated rats; group II included rats that were exposed for 28 consecutive days to natural radioactive rocks from the Egyptian eastern desert (IR/R group); and group III (positive control group) included rats that were exposed to high dose of γ-rays (4 Gy/14 days for 28 days) (IR/γR group). We found that rats of both the IR/R and IR/γR groups exhibited pathological alterations in the architecture of the primary immune organs (bone marrow and thymus). Additionally, the levels of C-reactive protein (CRP), proinflammatory cytokines (IL-1β, IL-6 and TNF-α), and reactive oxygen species (ROS) were significantly increased in the IR/R and IR/γR groups compared to the control group. Furthermore, rats from the IR/R and IR/γR groups exhibited significant increase in the activity of caspase-3 and caspase-9 and subsequently exhibited a significant increase in the apoptosis of PBMCs compared with the control group. Most importantly, apoptosis induction in the PBMCs was associated with increased expression of cyclin B1 and decreased expression of cyclin D1 and survivin compared with the control non-irradiated group. Taken together, our data demonstrated that consecutive exposure to natural radioactive rocks from the Egyptian eastern desert could dampen the immune response through damaging the architectures of the immune system and mediating serious health problems to the population inhabiting this region.