The Experts below are selected from a list of 2283 Experts worldwide ranked by ideXlab platform
Ranjith Kumavath - One of the best experts on this subject based on the ideXlab platform.
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Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers.
Frontiers in Oncology, 2020Co-Authors: Dhanasekhar Reddy, Preetam Ghosh, Ranjith KumavathAbstract:Lung cancer is the most prevalent in cancer-related deaths, while breast carcinoma is the second most dominant cancer in women, accounting for the most number of deaths worldwide. Cancers are heterogeneous diseases that consist of several subtypes based on the presence or absence of hormone receptors and human epidermal growth factor receptor 2. Several drugs have been developed targeting cancer biomarkers; nonetheless, their efficiency are not adequate due to the high reemergence rate of cancers and fundamental or acquired resistance toward such drugs, which leads to partial therapeutic possibilities. Recent studies on cardiac glycosides (CGs) positioned them as potent cytotoxic agents that target multiple pathways to initiate apoptosis and autophagic cell death in many cancers. In the present study, our aim is to identify the anticancer activity of a naturally available CG (Strophanthidin) in human breast (MCF-7), lung (A549), and liver cancer (HepG2) cells. Our results demonstrate a dose-dependent cytotoxic effect of Strophanthidin in MCF-7, A549, and HepG2 cells, which was further supported by DNA damage on drug treatment. Strophanthidin arrested the cell cycle at the G2/M phase; this effect was further validated by checking the inhibited expressions of checkpoint and cyclin-dependent kinases in Strophanthidin-induced cells. Moreover, Strophanthidin inhibited the expression of several key proteins such as MEK1, PI3K, AKT, mTOR, Gsk3α, and β-catenin from MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. The current study adequately exhibits the role of Strophanthidin in modulating the expression of various key proteins involved in cell cycle arrest, apoptosis, and autophagic cell death. Our in silico studies revealed that Strophanthidin can interact with several key proteins from various pathways. Taken together, this study demonstrates the viability of Strophanthidin as a promising anticancer agent, which may serve as a new anticancer drug.
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Strophanthidin attenuates mapk pi3k akt mtor and wnt β catenin signaling pathways in human cancers
Frontiers in Oncology, 2020Co-Authors: Dhanasekhar Reddy, Preetam Ghosh, Ranjith KumavathAbstract:Lung cancer is the most prevalent in cancer-related deaths, while breast carcinoma is the second most dominant cancer in women, accounting for the most number of deaths worldwide. Cancers are heterogeneous diseases that consist of several subtypes based on the presence or absence of hormone receptors and human epidermal growth factor receptor 2. Several drugs have been developed targeting cancer biomarkers; nonetheless, their efficiency are not adequate due to the high reemergence rate of cancers and fundamental or acquired resistance toward such drugs, which leads to partial therapeutic possibilities. Recent studies on cardiac glycosides (CGs) positioned them as potent cytotoxic agents that target multiple pathways to initiate apoptosis and autophagic cell death in many cancers. In the present study, our aim is to identify the anticancer activity of a naturally available CG (Strophanthidin) in human breast (MCF-7), lung (A549), and liver cancer (HepG2) cells. Our results demonstrate a dose-dependent cytotoxic effect of Strophanthidin in MCF-7, A549, and HepG2 cells, which was further supported by DNA damage on drug treatment. Strophanthidin arrested the cell cycle at the G2/M phase; this effect was further validated by checking the inhibited expressions of checkpoint and cyclin-dependent kinases in Strophanthidin-induced cells. Moreover, Strophanthidin inhibited the expression of several key proteins such as MEK1, PI3K, AKT, mTOR, Gsk3α, and β-catenin from MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. The current study adequately exhibits the role of Strophanthidin in modulating the expression of various key proteins involved in cell cycle arrest, apoptosis, and autophagic cell death. Our in silico studies revealed that Strophanthidin can interact with several key proteins from various pathways. Taken together, this study demonstrates the viability of Strophanthidin as a promising anticancer agent, which may serve as a new anticancer drug.
Dhanasekhar Reddy - One of the best experts on this subject based on the ideXlab platform.
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Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers.
Frontiers in Oncology, 2020Co-Authors: Dhanasekhar Reddy, Preetam Ghosh, Ranjith KumavathAbstract:Lung cancer is the most prevalent in cancer-related deaths, while breast carcinoma is the second most dominant cancer in women, accounting for the most number of deaths worldwide. Cancers are heterogeneous diseases that consist of several subtypes based on the presence or absence of hormone receptors and human epidermal growth factor receptor 2. Several drugs have been developed targeting cancer biomarkers; nonetheless, their efficiency are not adequate due to the high reemergence rate of cancers and fundamental or acquired resistance toward such drugs, which leads to partial therapeutic possibilities. Recent studies on cardiac glycosides (CGs) positioned them as potent cytotoxic agents that target multiple pathways to initiate apoptosis and autophagic cell death in many cancers. In the present study, our aim is to identify the anticancer activity of a naturally available CG (Strophanthidin) in human breast (MCF-7), lung (A549), and liver cancer (HepG2) cells. Our results demonstrate a dose-dependent cytotoxic effect of Strophanthidin in MCF-7, A549, and HepG2 cells, which was further supported by DNA damage on drug treatment. Strophanthidin arrested the cell cycle at the G2/M phase; this effect was further validated by checking the inhibited expressions of checkpoint and cyclin-dependent kinases in Strophanthidin-induced cells. Moreover, Strophanthidin inhibited the expression of several key proteins such as MEK1, PI3K, AKT, mTOR, Gsk3α, and β-catenin from MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. The current study adequately exhibits the role of Strophanthidin in modulating the expression of various key proteins involved in cell cycle arrest, apoptosis, and autophagic cell death. Our in silico studies revealed that Strophanthidin can interact with several key proteins from various pathways. Taken together, this study demonstrates the viability of Strophanthidin as a promising anticancer agent, which may serve as a new anticancer drug.
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Strophanthidin attenuates mapk pi3k akt mtor and wnt β catenin signaling pathways in human cancers
Frontiers in Oncology, 2020Co-Authors: Dhanasekhar Reddy, Preetam Ghosh, Ranjith KumavathAbstract:Lung cancer is the most prevalent in cancer-related deaths, while breast carcinoma is the second most dominant cancer in women, accounting for the most number of deaths worldwide. Cancers are heterogeneous diseases that consist of several subtypes based on the presence or absence of hormone receptors and human epidermal growth factor receptor 2. Several drugs have been developed targeting cancer biomarkers; nonetheless, their efficiency are not adequate due to the high reemergence rate of cancers and fundamental or acquired resistance toward such drugs, which leads to partial therapeutic possibilities. Recent studies on cardiac glycosides (CGs) positioned them as potent cytotoxic agents that target multiple pathways to initiate apoptosis and autophagic cell death in many cancers. In the present study, our aim is to identify the anticancer activity of a naturally available CG (Strophanthidin) in human breast (MCF-7), lung (A549), and liver cancer (HepG2) cells. Our results demonstrate a dose-dependent cytotoxic effect of Strophanthidin in MCF-7, A549, and HepG2 cells, which was further supported by DNA damage on drug treatment. Strophanthidin arrested the cell cycle at the G2/M phase; this effect was further validated by checking the inhibited expressions of checkpoint and cyclin-dependent kinases in Strophanthidin-induced cells. Moreover, Strophanthidin inhibited the expression of several key proteins such as MEK1, PI3K, AKT, mTOR, Gsk3α, and β-catenin from MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. The current study adequately exhibits the role of Strophanthidin in modulating the expression of various key proteins involved in cell cycle arrest, apoptosis, and autophagic cell death. Our in silico studies revealed that Strophanthidin can interact with several key proteins from various pathways. Taken together, this study demonstrates the viability of Strophanthidin as a promising anticancer agent, which may serve as a new anticancer drug.
Mario Vassalle - One of the best experts on this subject based on the ideXlab platform.
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The Relationship among Intracellular Sodium Activity, Calcium, and Strophanthidin Inotropy in Canine Cardiac Purkinje Fibers
2013Co-Authors: Mario Vassalle, C O LeeAbstract:ABSTRACT The role of sodium and calcium ions in Strophanthidin inotropy was studied by measuring simultaneously the electrical, mechanical, and intracellular sodium ion activities in electrically driven cardiac Purkinje fibers under conditions that change the intracellular sodium or calcium level (tetrodotoxin, Strophanthidin, high calcium, and norepinephrine). Tetrodotoxin (TTX; 1-5 X 10-s M) shifted the action potential plateau to more negative values, shortened the action potential duration, and decreased the contractile tension and the intracellular sodium ion activity (aN.). The changes in tension and in aN. caused by TTX appear to be related since they had similar time courses. Strophanthidin (2-5 X 10-7 M) increased tension and aNa less in the presence of TTX, and, for any given value of aN a, tension was less than in the absence of TTX. Increasing extracellular calcium (from 1.8 to 3.3-3.6 mM) or adding norepinephrine (0.5-1 X 10-s M) increased tension and decreased aNa less in the presence than in the absence of TTX. When two of the above procedures were combined, the results were different. Thus, during the increase in aNa and tension caused b
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role of intracellular na activity in the negative inotropy of Strophanthidin in cardiac purkinje fibers
European Journal of Pharmacology, 1992Co-Authors: P Abete, Mario VassalleAbstract:Abstract The relation between intracellular sodium activity (a Na i ) and different phases of Strophanthidin inotropy was studied in sheep cardiac Purkinje fibers superfused in vitro. Strophanthidin (1 μM) progressively increases a Na i whereas increases and then decreases contractile force, induces contracture (‘mechanical toxicity’) and arrhythmias (‘electrical toxicity’). Contractile force begins to decrease at ∼ 11 mM a Na i . Force and a Na i show a positive correlation during the increasing and a negative correlation during the decreasing phase of Strophanthidin inotropy. In high [K] o (8, 12 and 16 mM), Strophanthidin increases a Na i and force to a smaller peak and fails to induce toxicity. In high [Na] o (+18.5%), Strophanthidin increases a Na i and force to a larger peak and induced electrical toxicity below and mechanical toxicity above a higher a Na i value (∼ 15 mM). In higher [K] o , high [Na] o restores the ability of Strophanthidin to induce mechanical toxicity. Thus, mechanical toxicity begins when a Na i increases past a critical value and the continuing a Na i increase correlates with decrease in contractile force and contracture. The critical value of a Na i is modified by Ca load related to changes in membrane potential or to Na electrochemical gradient.
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Role of intracellular Na+ activity in the negative inotropy of Strophanthidin in cardiac Purkinje fibers.
European Journal of Pharmacology, 1992Co-Authors: P Abete, Mario VassalleAbstract:Abstract The relation between intracellular sodium activity (a Na i ) and different phases of Strophanthidin inotropy was studied in sheep cardiac Purkinje fibers superfused in vitro. Strophanthidin (1 μM) progressively increases a Na i whereas increases and then decreases contractile force, induces contracture (‘mechanical toxicity’) and arrhythmias (‘electrical toxicity’). Contractile force begins to decrease at ∼ 11 mM a Na i . Force and a Na i show a positive correlation during the increasing and a negative correlation during the decreasing phase of Strophanthidin inotropy. In high [K] o (8, 12 and 16 mM), Strophanthidin increases a Na i and force to a smaller peak and fails to induce toxicity. In high [Na] o (+18.5%), Strophanthidin increases a Na i and force to a larger peak and induced electrical toxicity below and mechanical toxicity above a higher a Na i value (∼ 15 mM). In higher [K] o , high [Na] o restores the ability of Strophanthidin to induce mechanical toxicity. Thus, mechanical toxicity begins when a Na i increases past a critical value and the continuing a Na i increase correlates with decrease in contractile force and contracture. The critical value of a Na i is modified by Ca load related to changes in membrane potential or to Na electrochemical gradient.
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Effects of Strophanthidin on the slow inward current in guinea-pig isolated ventricular myocytes.
Clinical and Experimental Pharmacology and Physiology, 1990Co-Authors: Lie Yang, Mario VassalleAbstract:SUMMARY 1. The effect of Strophanthidin on the slow inward current (Isi) and on contractile force were studied in guinea-pig isolated ventricular myocytes and intact papillary muscles, respectively. In myocytes, both low (10 nmol/L) and high (1–10 μmol/L) concentrations had small or no effects in either direction on Isi whereas norepinephrine (10–100 nmol/L) increased it. To determine whether the same results are obtained after decreasing or increasing intracellular calcium or sodium, the same concentrations of Strophanthidin were tested in different procedures that are known to (i) increase [Ca]i and decrease [Na]i (high [Ca]o, 3.6–5.4 mmol/L; low [Na]o, 112 mmol/L; (ii) decrease [Ca]i and increase [Na]i (low [Ca]o, 0.45–1 mmol/L; Sr, 1 mmol/L; (iii) decrease [Ca]i and [Na]i (Cd, 0.1–0.2 mmol/L); and (iv) increase [Ca]i and [Na]i (veratridine, 0.2 μmol/L). High [Ca]o and veratridine increased whereas low [Ca]o and Cd decreased Isi. In contrast, during these various procedures, Strophanthidin had small and inconsistent effects at a low or high concentration. In intact papillary muscles, low Strophanthidin decreased whereas high Strophanthidin increased contractile force. It is concluded that Strophanthidin has little direct or indirect effect on Isi and that the decrease in force by low and increase in force by high concentrations in intact muscle are probably related to demonstrated decrease and increase, respectively, in intracellular sodium activity.
Preetam Ghosh - One of the best experts on this subject based on the ideXlab platform.
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Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers.
Frontiers in Oncology, 2020Co-Authors: Dhanasekhar Reddy, Preetam Ghosh, Ranjith KumavathAbstract:Lung cancer is the most prevalent in cancer-related deaths, while breast carcinoma is the second most dominant cancer in women, accounting for the most number of deaths worldwide. Cancers are heterogeneous diseases that consist of several subtypes based on the presence or absence of hormone receptors and human epidermal growth factor receptor 2. Several drugs have been developed targeting cancer biomarkers; nonetheless, their efficiency are not adequate due to the high reemergence rate of cancers and fundamental or acquired resistance toward such drugs, which leads to partial therapeutic possibilities. Recent studies on cardiac glycosides (CGs) positioned them as potent cytotoxic agents that target multiple pathways to initiate apoptosis and autophagic cell death in many cancers. In the present study, our aim is to identify the anticancer activity of a naturally available CG (Strophanthidin) in human breast (MCF-7), lung (A549), and liver cancer (HepG2) cells. Our results demonstrate a dose-dependent cytotoxic effect of Strophanthidin in MCF-7, A549, and HepG2 cells, which was further supported by DNA damage on drug treatment. Strophanthidin arrested the cell cycle at the G2/M phase; this effect was further validated by checking the inhibited expressions of checkpoint and cyclin-dependent kinases in Strophanthidin-induced cells. Moreover, Strophanthidin inhibited the expression of several key proteins such as MEK1, PI3K, AKT, mTOR, Gsk3α, and β-catenin from MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. The current study adequately exhibits the role of Strophanthidin in modulating the expression of various key proteins involved in cell cycle arrest, apoptosis, and autophagic cell death. Our in silico studies revealed that Strophanthidin can interact with several key proteins from various pathways. Taken together, this study demonstrates the viability of Strophanthidin as a promising anticancer agent, which may serve as a new anticancer drug.
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Strophanthidin attenuates mapk pi3k akt mtor and wnt β catenin signaling pathways in human cancers
Frontiers in Oncology, 2020Co-Authors: Dhanasekhar Reddy, Preetam Ghosh, Ranjith KumavathAbstract:Lung cancer is the most prevalent in cancer-related deaths, while breast carcinoma is the second most dominant cancer in women, accounting for the most number of deaths worldwide. Cancers are heterogeneous diseases that consist of several subtypes based on the presence or absence of hormone receptors and human epidermal growth factor receptor 2. Several drugs have been developed targeting cancer biomarkers; nonetheless, their efficiency are not adequate due to the high reemergence rate of cancers and fundamental or acquired resistance toward such drugs, which leads to partial therapeutic possibilities. Recent studies on cardiac glycosides (CGs) positioned them as potent cytotoxic agents that target multiple pathways to initiate apoptosis and autophagic cell death in many cancers. In the present study, our aim is to identify the anticancer activity of a naturally available CG (Strophanthidin) in human breast (MCF-7), lung (A549), and liver cancer (HepG2) cells. Our results demonstrate a dose-dependent cytotoxic effect of Strophanthidin in MCF-7, A549, and HepG2 cells, which was further supported by DNA damage on drug treatment. Strophanthidin arrested the cell cycle at the G2/M phase; this effect was further validated by checking the inhibited expressions of checkpoint and cyclin-dependent kinases in Strophanthidin-induced cells. Moreover, Strophanthidin inhibited the expression of several key proteins such as MEK1, PI3K, AKT, mTOR, Gsk3α, and β-catenin from MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. The current study adequately exhibits the role of Strophanthidin in modulating the expression of various key proteins involved in cell cycle arrest, apoptosis, and autophagic cell death. Our in silico studies revealed that Strophanthidin can interact with several key proteins from various pathways. Taken together, this study demonstrates the viability of Strophanthidin as a promising anticancer agent, which may serve as a new anticancer drug.
Gerhard Giebisch - One of the best experts on this subject based on the ideXlab platform.
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relationship between sodium transport and intracellular atp in isolated perfused rabbit proximal convoluted tubule
American Journal of Physiology-renal Physiology, 1991Co-Authors: J S Beck, Raynald Laprade, Heimo Mairbaurl, Sylvie Breton, Gerhard GiebischAbstract:: The effect of alterations in sodium transport on cell ATP content and pH in the isolated perfused proximal convoluted tubule (PCT) of the rabbit was examined. Stimulating sodium transport by the addition of luminal glucose and alanine decreased cell ATP from 4.44 +/- 0.93 to 2.69 +/- 0.62 mM (n = 4), increased intracellular pH by 0.13 +/- 0.02 (n = 7), and increased cell volume by 0.10 +/- 0.02 nl/mm (n = 4). Blocking the sodium pump with 10(-4) M Strophanthidin in tubules in which sodium transport had been stimulated increased cell ATP from 2.04 +/- 0.24 to 2.42 +/- 0.32 mM (n = 6). In parallel experiments the same dose of Strophanthidin depolarized the basolateral membrane from -52.6 +/- 1.9 to -6.4 +/- 1.6 mV, depolarized the transepithelial potential from -3.2 +/- 0.3 to -0.1 +/- 0.1 mV, and reduced the basolateral membrane potassium transference number from 0.47 to 0.26 indicating a reduction in basolateral potassium conductance. Since Strophanthidin caused a cell alkalinization of 0.15 +/- 0.03, this latter effect cannot be due to changes of intracellular pH. Strophanthidin caused no change in cell volume over the period studied, suggesting that stretch-activated potassium channels are not involved either. Instead, potassium conductance inhibition may be the result of the closure of ATP-sensitive potassium channels. These same channels might thus be partly responsible for the increase in potassium conductance commonly observed during stimulation of sodium transport.
