As per the latest Globocan statistics,the high prevalence rate of breast cancer in low-and middle-income countries has led to it becoming the most common cancer to be diagnosed,hence posing a major public health chall...As per the latest Globocan statistics,the high prevalence rate of breast cancer in low-and middle-income countries has led to it becoming the most common cancer to be diagnosed,hence posing a major public health challenge.As per this data,more than 11.7%of the estimated new cancer cases in 2020 were due to breast cancer.A small but significant subpopulation of cells with self-renewing ability are present in the tumor stroma and have been given the nomenclature of cancer stem cells(CSCs).These cells display a high degree of plasticity owing to their ability to transition from the slowly cycling quiescent phase to the actively proliferating phenotype.This attribute of CSCs allows them to differentiate into various cell types having diverse functions.Breast CSCs have a pivotal role in development,metastasis,treatment resistance and relapse of breast cancers.This review focuses on the pathways regulating breast CSC maintenance and the current strategies that are being explored for directing the development of novel,targeted,therapeutic approaches for limiting and eradicating this aberrant stem cell population.展开更多
Objective: Prolonged use of nonsteroidal anti-inflammatory drugs is associated with severe side effects and toxicity. Therefore, we studied the anti-inflammatory role of Calcarea carbonica which had minimal toxicity a...Objective: Prolonged use of nonsteroidal anti-inflammatory drugs is associated with severe side effects and toxicity. Therefore, we studied the anti-inflammatory role of Calcarea carbonica which had minimal toxicity at the low doses.Methods: THP-1 human mononuclear cells were treated with C. carbonica to evaluate the 50% cytotoxicity concentration(CC_(50)) and 50% effective concentration(EC_(50)). Cell survival was evaluated in lipopolysaccharide-stimulated C. carbonica-treated cells. Nitric oxide(NO) and tumor necrosis factor-a(TNF-a) were measured to evaluate the anti-inflammatory activity of C. carbonica. Cyclooxygenase-2(COX-2) protein expression was determined by Western blotting analysis, and the interaction of C. carbonica with the COX-2 protein was evaluated using molecular docking simulation.Results: The CC_(50) and EC_(50) of C. carbonica were found to be 43.26 and 11.99 mg/mL, respectively. The cell survival assay showed a 1.192-fold(P = 0.0129), 1.443-fold(P = 0.0009) and 1.605-fold(P = 0.0004)increase in cell survival at 24, 48 and 72 h after initiating C. carbonica treatment, respectively. C. carbonica-treated cells showed a reduction in NO levels by 2.355 folds(P = 0.0001), 2.181 folds(P = 0.0001) and 2.071 folds(P = 0.0001) at 24, 48 and 72 h, respectively. The treated cells also showed a reduction in TNFa levels by 1.395 folds(P = 0.0013), 1.541 folds(P = 0.0005) and 1.550 folds(P = 0.0005) at 24, 48 and72 h, respectively. In addition, a 1.193-fold reduction(P = 0.0126) in COX-2 protein expression was found in C. carbonica-treated cells. The molecular docking showed interaction of C. carbonica with the phenylalanine 367 residue present in active site of Cox-2.Conclusion: C. carbonica exhibited anti-inflammatory properties in lipopolysaccharide-stimulated cells by significantly reducing NO production and TNF-a level through downregulation of the COX-2 protein. This effect is probably mediated through interaction of C. carbonica with the phenylalanine 367 residue present in active site of Cox-2.展开更多
基金Supported by Central Council for Research in Homeopathy(CCRH),AYUSH(Govt.of India),No.17-03/2019-20/CCRH/Tech/Coll/Amity/7284.
文摘As per the latest Globocan statistics,the high prevalence rate of breast cancer in low-and middle-income countries has led to it becoming the most common cancer to be diagnosed,hence posing a major public health challenge.As per this data,more than 11.7%of the estimated new cancer cases in 2020 were due to breast cancer.A small but significant subpopulation of cells with self-renewing ability are present in the tumor stroma and have been given the nomenclature of cancer stem cells(CSCs).These cells display a high degree of plasticity owing to their ability to transition from the slowly cycling quiescent phase to the actively proliferating phenotype.This attribute of CSCs allows them to differentiate into various cell types having diverse functions.Breast CSCs have a pivotal role in development,metastasis,treatment resistance and relapse of breast cancers.This review focuses on the pathways regulating breast CSC maintenance and the current strategies that are being explored for directing the development of novel,targeted,therapeutic approaches for limiting and eradicating this aberrant stem cell population.
基金supported by Central Council for Research in Homoeopathy,Ministry of Ayush,Government of India。
文摘Objective: Prolonged use of nonsteroidal anti-inflammatory drugs is associated with severe side effects and toxicity. Therefore, we studied the anti-inflammatory role of Calcarea carbonica which had minimal toxicity at the low doses.Methods: THP-1 human mononuclear cells were treated with C. carbonica to evaluate the 50% cytotoxicity concentration(CC_(50)) and 50% effective concentration(EC_(50)). Cell survival was evaluated in lipopolysaccharide-stimulated C. carbonica-treated cells. Nitric oxide(NO) and tumor necrosis factor-a(TNF-a) were measured to evaluate the anti-inflammatory activity of C. carbonica. Cyclooxygenase-2(COX-2) protein expression was determined by Western blotting analysis, and the interaction of C. carbonica with the COX-2 protein was evaluated using molecular docking simulation.Results: The CC_(50) and EC_(50) of C. carbonica were found to be 43.26 and 11.99 mg/mL, respectively. The cell survival assay showed a 1.192-fold(P = 0.0129), 1.443-fold(P = 0.0009) and 1.605-fold(P = 0.0004)increase in cell survival at 24, 48 and 72 h after initiating C. carbonica treatment, respectively. C. carbonica-treated cells showed a reduction in NO levels by 2.355 folds(P = 0.0001), 2.181 folds(P = 0.0001) and 2.071 folds(P = 0.0001) at 24, 48 and 72 h, respectively. The treated cells also showed a reduction in TNFa levels by 1.395 folds(P = 0.0013), 1.541 folds(P = 0.0005) and 1.550 folds(P = 0.0005) at 24, 48 and72 h, respectively. In addition, a 1.193-fold reduction(P = 0.0126) in COX-2 protein expression was found in C. carbonica-treated cells. The molecular docking showed interaction of C. carbonica with the phenylalanine 367 residue present in active site of Cox-2.Conclusion: C. carbonica exhibited anti-inflammatory properties in lipopolysaccharide-stimulated cells by significantly reducing NO production and TNF-a level through downregulation of the COX-2 protein. This effect is probably mediated through interaction of C. carbonica with the phenylalanine 367 residue present in active site of Cox-2.
