The Experts below are selected from a list of 16059 Experts worldwide ranked by ideXlab platform
Xiaoxing Feng - One of the best experts on this subject based on the ideXlab platform.
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Enhanced cytotoxicity in triple-negative and estrogen receptor‑positive Breast Adenocarcinoma cells due to inhibition of the transient receptor potential melastatin-2 channel
Oncology reports, 2015Co-Authors: David W. Koh, Mandi M. Hopkins, Daniel P. Powell, Steven D. Blake, Joy L. Hoffman, Xiaoxing FengAbstract:We previously demonstrated a unique protective role for the transient receptor potential, melastatin-2 (TRPM2) cation channel in Breast cancer cells. In the present study, we investigated the chemotherapeutic effects elicited by inhibiting this protective role in metastatic Breast Adenocarcinoma cells. TRPM2 inhibition led to dose-dependent increases in MDA-MB-231 Breast Adenocarcinoma cell death after treatment with doxorubicin or the DNA-methylating agent, N-methyl-N'-nitro-N-nitrosoguanidine. Similar results were observed after RNAi silencing of TRPM2 in these cells after doxorubicin treatment. However, TRPM2 RNAi silencing also led to increased MCF-7 Breast Adenocarcinoma cell death after tamoxifen treatment, yet not in non-cancerous human mammary epithelial cells. These results thus revealed that TRPM2 inhibition selectively increased cytotoxicity in a triple-negative and an estrogen receptor-positive Breast cancer cell line, with minimal deleterious effects in non-cancerous Breast cells. Analysis of DNA damage revealed enhanced DNA damage levels in MCF-7 cells treated with doxorubicin due to TRPM2 inhibition. Analysis of cell death demonstrated that inhibition of apoptosis, caspase-independent cell death or autophagy failed to significantly reduce cell death induced by TRPM2 inhibition and chemotherapy. These results indicate that TRPM2 inhibition activates alternative pathways of cell death in Breast cancer cells. Taken together, our results provide significant evidence that TRPM2 inhibition is a potential strategy to induce triple-negative and estrogen receptor-positive Breast Adenocarcinoma cell death via alternative cell death pathways. This is expected to provide a basis for inhibiting TRPM2 for the improved treatment of Breast cancer, which potentially includes treating Breast tumors that are resistant to chemotherapy due to their evasion of apoptosis.
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Inhibition of the transient receptor potential melastatin-2 channel causes increased DNA damage and decreased proliferation in Breast Adenocarcinoma cells.
International journal of oncology, 2015Co-Authors: Mandi M. Hopkins, Xiaoxing Feng, Mengwei Liu, Lauren P. Parker, David W. KohAbstract:Transient receptor potential, melastatin-2 (TRPM2) is a plasma membrane cation channel with important roles in sensory functions and promoting cell death. However, we demonstrated here that TRPM2 was present in the nuclei of MCF-7 and MDA-MB-231 human Breast Adenocarcinoma cells, and its pharmacologic inhibition or RNAi silencing caused decreased cell proliferation. Neither an effect on proliferation nor a localization of TRPM2 in the nucleus was observed in noncancerous HMEC and MCF-10A human mammary epithelial cells. Investigation of possible effects of TRPM2 function in the nucleus demonstrated that pharmacologic inhibition or RNAi silencing of TRPM2 in MCF-7 and MDA-MB-231 human Breast Adenocarcinoma cells caused up to 4-fold increases in DNA damage levels, as compared to noncancerous Breast cells after equivalent treatments. These results indicate that TRPM2 has a novel nuclear function in human Breast Adenocarcinoma cells that facilitates the integrity of genomic DNA, a finding that is distinct from its previously reported role as a plasma membrane cation channel in noncancerous cells. In summary, we report here a novel effect promoted by TRPM2, where it functions to minimize DNA damage and thus may have a role in the protection of genomic DNA in Breast cancer cells. Our study therefore provides compelling evidence that TRPM2 has a unique role in Breast Adenocarcinoma cells. Accordingly, these studies suggest that TRPM2 is a potential therapeutic target, where its pharmacologic inhibition may provide an innovative strategy to selectively increase DNA damage levels in Breast cancer cells.
David W. Koh - One of the best experts on this subject based on the ideXlab platform.
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Enhanced cytotoxicity in triple-negative and estrogen receptor‑positive Breast Adenocarcinoma cells due to inhibition of the transient receptor potential melastatin-2 channel
Oncology reports, 2015Co-Authors: David W. Koh, Mandi M. Hopkins, Daniel P. Powell, Steven D. Blake, Joy L. Hoffman, Xiaoxing FengAbstract:We previously demonstrated a unique protective role for the transient receptor potential, melastatin-2 (TRPM2) cation channel in Breast cancer cells. In the present study, we investigated the chemotherapeutic effects elicited by inhibiting this protective role in metastatic Breast Adenocarcinoma cells. TRPM2 inhibition led to dose-dependent increases in MDA-MB-231 Breast Adenocarcinoma cell death after treatment with doxorubicin or the DNA-methylating agent, N-methyl-N'-nitro-N-nitrosoguanidine. Similar results were observed after RNAi silencing of TRPM2 in these cells after doxorubicin treatment. However, TRPM2 RNAi silencing also led to increased MCF-7 Breast Adenocarcinoma cell death after tamoxifen treatment, yet not in non-cancerous human mammary epithelial cells. These results thus revealed that TRPM2 inhibition selectively increased cytotoxicity in a triple-negative and an estrogen receptor-positive Breast cancer cell line, with minimal deleterious effects in non-cancerous Breast cells. Analysis of DNA damage revealed enhanced DNA damage levels in MCF-7 cells treated with doxorubicin due to TRPM2 inhibition. Analysis of cell death demonstrated that inhibition of apoptosis, caspase-independent cell death or autophagy failed to significantly reduce cell death induced by TRPM2 inhibition and chemotherapy. These results indicate that TRPM2 inhibition activates alternative pathways of cell death in Breast cancer cells. Taken together, our results provide significant evidence that TRPM2 inhibition is a potential strategy to induce triple-negative and estrogen receptor-positive Breast Adenocarcinoma cell death via alternative cell death pathways. This is expected to provide a basis for inhibiting TRPM2 for the improved treatment of Breast cancer, which potentially includes treating Breast tumors that are resistant to chemotherapy due to their evasion of apoptosis.
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Inhibition of the transient receptor potential melastatin-2 channel causes increased DNA damage and decreased proliferation in Breast Adenocarcinoma cells.
International journal of oncology, 2015Co-Authors: Mandi M. Hopkins, Xiaoxing Feng, Mengwei Liu, Lauren P. Parker, David W. KohAbstract:Transient receptor potential, melastatin-2 (TRPM2) is a plasma membrane cation channel with important roles in sensory functions and promoting cell death. However, we demonstrated here that TRPM2 was present in the nuclei of MCF-7 and MDA-MB-231 human Breast Adenocarcinoma cells, and its pharmacologic inhibition or RNAi silencing caused decreased cell proliferation. Neither an effect on proliferation nor a localization of TRPM2 in the nucleus was observed in noncancerous HMEC and MCF-10A human mammary epithelial cells. Investigation of possible effects of TRPM2 function in the nucleus demonstrated that pharmacologic inhibition or RNAi silencing of TRPM2 in MCF-7 and MDA-MB-231 human Breast Adenocarcinoma cells caused up to 4-fold increases in DNA damage levels, as compared to noncancerous Breast cells after equivalent treatments. These results indicate that TRPM2 has a novel nuclear function in human Breast Adenocarcinoma cells that facilitates the integrity of genomic DNA, a finding that is distinct from its previously reported role as a plasma membrane cation channel in noncancerous cells. In summary, we report here a novel effect promoted by TRPM2, where it functions to minimize DNA damage and thus may have a role in the protection of genomic DNA in Breast cancer cells. Our study therefore provides compelling evidence that TRPM2 has a unique role in Breast Adenocarcinoma cells. Accordingly, these studies suggest that TRPM2 is a potential therapeutic target, where its pharmacologic inhibition may provide an innovative strategy to selectively increase DNA damage levels in Breast cancer cells.
Abeer E. Mahmoud - One of the best experts on this subject based on the ideXlab platform.
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synthesis and in vitro cytotoxic activity of novel pyrazolo 3 4 d pyrimidines and related pyrazole hydrazones toward Breast Adenocarcinoma mcf 7 cell line
Bioorganic & Medicinal Chemistry, 2011Co-Authors: Ghaneya S Hassan, Hanan H Kadry, Sahar M Abouseri, Abeer E. MahmoudAbstract:Abstract New series of pyrazolo[3,4- d ]pyrimidines ( 7a–e and 13a–d ) and pyrazole hydrazones 17a–d were synthesized and evaluated for their antiproliferative activity against human Breast Adenocarcinoma MCF-7 cell line. Most of the tested compounds exploited potent to moderate growth inhibitory activity, in particular compound 7e exhibited superior potency to the reference drug cisplatin (IC 50 = 7.60 and 13.29 μM, respectively). The antitumor activity of the new compounds was accompanied by significant increase in the activity of superoxide dismutase with concomitant decrease in the activities of catalase and glutathione peroxidase and reduced glutathione level. Accordingly, the overproduction of hydrogen peroxide, nitric oxide and other free radicals allowed reactive oxygen species (ROS)-mediated tumor cells death, as monitored by reduction in the synthesis of protein and nucleic acids.
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Synthesis and Anticancer Effects of Some Novel Pyrazolo[3,4‐d]pyrimidine Derivatives by Generating Reactive Oxygen Species in Human Breast Adenocarcinoma Cells.
ChemInform, 2011Co-Authors: Aymn E. Rashad, Abeer E. Mahmoud, Mamdouh M. AliAbstract:Synthesis and in vitro cytotoxicity tests against human Breast Adenocarcinoma (MCF-7) are given.
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synthesis and anticancer effects of some novel pyrazolo 3 4 d pyrimidine derivatives by generating reactive oxygen species in human Breast Adenocarcinoma cells
European Journal of Medicinal Chemistry, 2011Co-Authors: Aymn E. Rashad, Abeer E. Mahmoud, Mamdouh M. AliAbstract:Abstract A series of novel substituted pyrazolo[3,4- d ]pyrimidines (compounds 2 – 12 ) were synthesized starting with pyrimidinone derivative 1 . Their in vitro cytotoxicity against human Breast Adenocarcinoma (MCF-7) cell lines has been investigated and most of the tested compounds exploited potent cytotoxic activity against MCF-7 cell lines comparable to the activity of the commonly used anticancer drug cisplatin. Treatment of MCF-7 cells with increased doses (2, 5, 10, 20 μg/ml) of the tested compounds revealed that the activity of superoxide dismutase and the level of hydrogen peroxide were significantly increased, while the activities of catalase and glutathione peroxidase and the levels of reduced glutathione were significantly lowered compared with control MCF-7 cells. In general, acyclic nucleoside derivative 4 revealed the highest anticancer activity among the other tested compounds.
Mandi M. Hopkins - One of the best experts on this subject based on the ideXlab platform.
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Enhanced cytotoxicity in triple-negative and estrogen receptor‑positive Breast Adenocarcinoma cells due to inhibition of the transient receptor potential melastatin-2 channel
Oncology reports, 2015Co-Authors: David W. Koh, Mandi M. Hopkins, Daniel P. Powell, Steven D. Blake, Joy L. Hoffman, Xiaoxing FengAbstract:We previously demonstrated a unique protective role for the transient receptor potential, melastatin-2 (TRPM2) cation channel in Breast cancer cells. In the present study, we investigated the chemotherapeutic effects elicited by inhibiting this protective role in metastatic Breast Adenocarcinoma cells. TRPM2 inhibition led to dose-dependent increases in MDA-MB-231 Breast Adenocarcinoma cell death after treatment with doxorubicin or the DNA-methylating agent, N-methyl-N'-nitro-N-nitrosoguanidine. Similar results were observed after RNAi silencing of TRPM2 in these cells after doxorubicin treatment. However, TRPM2 RNAi silencing also led to increased MCF-7 Breast Adenocarcinoma cell death after tamoxifen treatment, yet not in non-cancerous human mammary epithelial cells. These results thus revealed that TRPM2 inhibition selectively increased cytotoxicity in a triple-negative and an estrogen receptor-positive Breast cancer cell line, with minimal deleterious effects in non-cancerous Breast cells. Analysis of DNA damage revealed enhanced DNA damage levels in MCF-7 cells treated with doxorubicin due to TRPM2 inhibition. Analysis of cell death demonstrated that inhibition of apoptosis, caspase-independent cell death or autophagy failed to significantly reduce cell death induced by TRPM2 inhibition and chemotherapy. These results indicate that TRPM2 inhibition activates alternative pathways of cell death in Breast cancer cells. Taken together, our results provide significant evidence that TRPM2 inhibition is a potential strategy to induce triple-negative and estrogen receptor-positive Breast Adenocarcinoma cell death via alternative cell death pathways. This is expected to provide a basis for inhibiting TRPM2 for the improved treatment of Breast cancer, which potentially includes treating Breast tumors that are resistant to chemotherapy due to their evasion of apoptosis.
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Inhibition of the transient receptor potential melastatin-2 channel causes increased DNA damage and decreased proliferation in Breast Adenocarcinoma cells.
International journal of oncology, 2015Co-Authors: Mandi M. Hopkins, Xiaoxing Feng, Mengwei Liu, Lauren P. Parker, David W. KohAbstract:Transient receptor potential, melastatin-2 (TRPM2) is a plasma membrane cation channel with important roles in sensory functions and promoting cell death. However, we demonstrated here that TRPM2 was present in the nuclei of MCF-7 and MDA-MB-231 human Breast Adenocarcinoma cells, and its pharmacologic inhibition or RNAi silencing caused decreased cell proliferation. Neither an effect on proliferation nor a localization of TRPM2 in the nucleus was observed in noncancerous HMEC and MCF-10A human mammary epithelial cells. Investigation of possible effects of TRPM2 function in the nucleus demonstrated that pharmacologic inhibition or RNAi silencing of TRPM2 in MCF-7 and MDA-MB-231 human Breast Adenocarcinoma cells caused up to 4-fold increases in DNA damage levels, as compared to noncancerous Breast cells after equivalent treatments. These results indicate that TRPM2 has a novel nuclear function in human Breast Adenocarcinoma cells that facilitates the integrity of genomic DNA, a finding that is distinct from its previously reported role as a plasma membrane cation channel in noncancerous cells. In summary, we report here a novel effect promoted by TRPM2, where it functions to minimize DNA damage and thus may have a role in the protection of genomic DNA in Breast cancer cells. Our study therefore provides compelling evidence that TRPM2 has a unique role in Breast Adenocarcinoma cells. Accordingly, these studies suggest that TRPM2 is a potential therapeutic target, where its pharmacologic inhibition may provide an innovative strategy to selectively increase DNA damage levels in Breast cancer cells.
Mamdouh M. Ali - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and Anticancer Effects of Some Novel Pyrazolo[3,4‐d]pyrimidine Derivatives by Generating Reactive Oxygen Species in Human Breast Adenocarcinoma Cells.
ChemInform, 2011Co-Authors: Aymn E. Rashad, Abeer E. Mahmoud, Mamdouh M. AliAbstract:Synthesis and in vitro cytotoxicity tests against human Breast Adenocarcinoma (MCF-7) are given.
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synthesis and anticancer effects of some novel pyrazolo 3 4 d pyrimidine derivatives by generating reactive oxygen species in human Breast Adenocarcinoma cells
European Journal of Medicinal Chemistry, 2011Co-Authors: Aymn E. Rashad, Abeer E. Mahmoud, Mamdouh M. AliAbstract:Abstract A series of novel substituted pyrazolo[3,4- d ]pyrimidines (compounds 2 – 12 ) were synthesized starting with pyrimidinone derivative 1 . Their in vitro cytotoxicity against human Breast Adenocarcinoma (MCF-7) cell lines has been investigated and most of the tested compounds exploited potent cytotoxic activity against MCF-7 cell lines comparable to the activity of the commonly used anticancer drug cisplatin. Treatment of MCF-7 cells with increased doses (2, 5, 10, 20 μg/ml) of the tested compounds revealed that the activity of superoxide dismutase and the level of hydrogen peroxide were significantly increased, while the activities of catalase and glutathione peroxidase and the levels of reduced glutathione were significantly lowered compared with control MCF-7 cells. In general, acyclic nucleoside derivative 4 revealed the highest anticancer activity among the other tested compounds.