The Experts below are selected from a list of 23631 Experts worldwide ranked by ideXlab platform
S Kannan - One of the best experts on this subject based on the ideXlab platform.
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induction of ros dependent mitochondria mediated Intrinsic Apoptosis in mda mb 231 cells by glycoprotein from codium decorticatum
Journal of Agricultural and Food Chemistry, 2014Co-Authors: Ramar Thangam, Dharmaraj Senthilkumar, Veeraperumal Suresh, Malairaj Sathuvan, Srinivasan Sivasubramanian, K Pazhanichamy, Praveen Kumar Gorlagunta, S KannanAbstract:Marine macroalgae consist of a range of bioactive molecules exhibiting different biological activities, and many of these properties are attributed to sulfated polysaccharides, fucoxanthin, phycobiliproteins, and halogenated compounds. In this study, a glycoprotein (GLP) with a molecular mass of ∼48 kDa was extracted and purified from Codium decorticatum and investigated for its cytotoxic properties against human MDA-MB-231 breast cancer cells. The IC50 values of GLP against MDA-MB-231 and normal breast HBL-100 cells (control) were 75 ± 0.23 μg/mL (IC25), 55 ± 0.32 μg/mL (IC50), and 30 ± 0.43 μg/mL (IC75) and 90 ± 0.57 μg/mL (IC25), 80 ± 0.48 μg/mL (IC50), and 60 ± 0.26 μg/mL (IC75), respectively. Chromatin condensation and poly(ADP-ribose) polymerase (PARP) cleavage studies showed that the GLP inhibited cell viability by inducing Apoptosis in MDA-MB-231 cells. Induction of mitochondria-mediated Intrinsic apoptotic pathway by GLP was evidenced by the events of loss of mitochondrial membrane potential (ΔΨm...
Jong Seung Kim - One of the best experts on this subject based on the ideXlab platform.
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mitochondrial induced and self monitored Intrinsic Apoptosis by antitumor theranostic prodrug in vivo imaging and precise cancer treatment
Journal of the American Chemical Society, 2014Co-Authors: Rajesh Kumar, Jiyou Han, Hee-joung Lim, Wen Xiu Ren, Ja-yun Lim, Jong-hoon Kim, Jong Seung KimAbstract:Activation of Apoptosis, the cell death machinery, in tumor cells by organelle-specific delivery of antitumor theranostic agent is the utmost challenge in cancer therapy. Herein, we developed a highly efficient mitochondria-targeting antitumor theranostic prodrug 7 that contained two molecules of drug 5′-deoxy-5-fluorouridine and an apoptotic marker ethidium for self-monitoring Intrinsic (mitochondrial) Apoptosis after its activation in tumor cells. Theranostic 7 was activated by endogenously produced mitochondrial-overexpressed H2O2 and released drug 5′-deoxy-5-fluorouridine and apoptotic marker ethidium to the tumor cells. The in vitro and in vivo drug release was monitored by observing the fluorescence changes of ethidium. Theranostic 7 exhibited an enhanced cytotoxicity over commercial 5-fluorouracil (an active drug of 5′-deoxy-5-fluorouridine) leading to Intrinsic Apoptosis monitored by in situ generated ethidium. Enhanced expression of mitochondria-mediated apoptotic genes (NOXA, PUMA, BID, BAX, and...
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Mitochondrial Induced and Self-Monitored Intrinsic Apoptosis by Antitumor Theranostic Prodrug: In Vivo Imaging and Precise Cancer Treatment
2014Co-Authors: Rajesh Kumar, Jiyou Han, Hee-joung Lim, Wen Xiu Ren, Ja-yun Lim, Jong-hoon Kim, Jong Seung KimAbstract:Activation of Apoptosis, the cell death machinery, in tumor cells by organelle-specific delivery of antitumor theranostic agent is the utmost challenge in cancer therapy. Herein, we developed a highly efficient mitochondria-targeting antitumor theranostic prodrug 7 that contained two molecules of drug 5′-deoxy-5-fluorouridine and an apoptotic marker ethidium for self-monitoring Intrinsic (mitochondrial) Apoptosis after its activation in tumor cells. Theranostic 7 was activated by endogenously produced mitochondrial-overexpressed H2O2 and released drug 5′-deoxy-5-fluorouridine and apoptotic marker ethidium to the tumor cells. The in vitro and in vivo drug release was monitored by observing the fluorescence changes of ethidium. Theranostic 7 exhibited an enhanced cytotoxicity over commercial 5-fluorouracil (an active drug of 5′-deoxy-5-fluorouridine) leading to Intrinsic Apoptosis monitored by in situ generated ethidium. Enhanced expression of mitochondria-mediated apoptotic genes (NOXA, PUMA, BID, BAX, and BAK), Cyt C, Caspase-3 and -9, and cell surface death receptors was observed after theranostic 7 activation in tumor cells. In vivo and ex vivo xenografts revealed that theranostic 7 significantly inhibited tumor progression and cured the tumor-bearing mice. Such organelle-specific theranostic strategies have great potential for the early diagnosis and precise treatment of cancer
Ramar Thangam - One of the best experts on this subject based on the ideXlab platform.
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induction of ros dependent mitochondria mediated Intrinsic Apoptosis in mda mb 231 cells by glycoprotein from codium decorticatum
Journal of Agricultural and Food Chemistry, 2014Co-Authors: Ramar Thangam, Dharmaraj Senthilkumar, Veeraperumal Suresh, Malairaj Sathuvan, Srinivasan Sivasubramanian, K Pazhanichamy, Praveen Kumar Gorlagunta, S KannanAbstract:Marine macroalgae consist of a range of bioactive molecules exhibiting different biological activities, and many of these properties are attributed to sulfated polysaccharides, fucoxanthin, phycobiliproteins, and halogenated compounds. In this study, a glycoprotein (GLP) with a molecular mass of ∼48 kDa was extracted and purified from Codium decorticatum and investigated for its cytotoxic properties against human MDA-MB-231 breast cancer cells. The IC50 values of GLP against MDA-MB-231 and normal breast HBL-100 cells (control) were 75 ± 0.23 μg/mL (IC25), 55 ± 0.32 μg/mL (IC50), and 30 ± 0.43 μg/mL (IC75) and 90 ± 0.57 μg/mL (IC25), 80 ± 0.48 μg/mL (IC50), and 60 ± 0.26 μg/mL (IC75), respectively. Chromatin condensation and poly(ADP-ribose) polymerase (PARP) cleavage studies showed that the GLP inhibited cell viability by inducing Apoptosis in MDA-MB-231 cells. Induction of mitochondria-mediated Intrinsic apoptotic pathway by GLP was evidenced by the events of loss of mitochondrial membrane potential (ΔΨm...
Yi Charlie Chen - One of the best experts on this subject based on the ideXlab platform.
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kaempferol induces Apoptosis in ovarian cancer cells through activating p53 in the Intrinsic pathway
Food Chemistry, 2011Co-Authors: Haitao Luo, Gary O Rankin, Laura Depriest, Yi Charlie ChenAbstract:Abstract Ovarian cancer is a significant malignancy for women in the Western world, and its death rate has remained unchanged over the past 50 years, leaving room for proper chemoprevention. Kaempferol is a natural flavonoid widely distributed in fruits and vegetables, and epidemiological studies have found a negative correlation between kaempferol consumption and ovarian cancer risk. To understand the mechanism behind this negative correlation, we investigated kaempferol’s ability to induce Apoptosis in A2780/CP70, A2780/wt, and OVCAR-3 ovarian cancer cell lines. Kaempferol inhibited cell proliferation but did not cause necrosis in all 3 cell lines. For the Apoptosis, caspase 3/7 levels were induced in a concentration-dependent manner by kaempferol treatment, with A2780/wt cells being the most responsive. This induction can be diminished by pre-treatment with a caspase-9 inhibitor, indicating an Intrinsic Apoptosis pathway. Western blot analysis revealed that protein levels of Bcl-xL were decreased in ovarian cancer cells, whilst p53, Bad, and Bax proteins were up-regulated by kaempferol treatment. Our data indicate that kaempferol induces Apoptosis in ovarian cancer cells through regulating pro-apoptotic and anti-apoptotic protein expressions in the Intrinsic Apoptosis pathways, and is a good candidate for the chemoprevention of ovarian cancers in humans. Further studies in animal models and clinical trials are therefore warranted.
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kaempferol induces Apoptosis in ovarian cancer cells through activating p53 in the Intrinsic pathway
Food Chemistry, 2011Co-Authors: Haitao Luo, Gary O Rankin, Laura Depriest, Yi Charlie ChenAbstract:Ovarian cancer is a significant malignancy for women in the western world, and its death rate has remained unchanged over the past 50 years, leaving room for proper chemoprevention. Kaempferol is a natural flavonoid widely distributed in fruits and vegetables, and epidemiological studies have found a negative correlation between kaempferol consumption and ovarian cancer risk. To understand the mechanism behind this negative correlation, we investigated kaempferol's ability to induce Apoptosis in A2780/CP70, A2780/wt, and OVCAR-3 ovarian cancer cell lines. Kaempferol inhibited cell proliferation but did not cause necrosis in all 3 cell lines. For the Apoptosis, caspase 3/7 levels were induced in a concentration-dependent manner by kaempferol treatment, with A2780/wt cells being the most responsive. This induction can be diminished by pre-treatment with a caspase-9 inhibitor, indicating an Intrinsic Apoptosis pathway. Western blot analysis revealed that protein levels of Bcl-x(L) were decreased in ovarian cancer cells, while p53, Bad, and Bax proteins were up-regulated by kaempferol treatment. Our data indicate that kaempferol induces Apoptosis in ovarian cancer cells through regulating pro-apoptotic and anti-apoptotic protein expressions in the Intrinsic Apoptosis pathways, and is a good candidate for the chemoprevention of ovarian cancers in humans. Further studies in animal models and clinical trials are therefore warranted.
Simone Fulda - One of the best experts on this subject based on the ideXlab platform.
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next generation hypomethylating agent sgi 110 primes acute myeloid leukemia cells to iap antagonist by activating extrinsic and Intrinsic Apoptosis pathways
Cell Death & Differentiation, 2020Co-Authors: Jessica Dittmann, Tinka Haydn, Patrick Metzger, George Ward, Melanie Boerries, Meike Vogler, Simone FuldaAbstract:Therapeutic efficacy of first-generation hypomethylating agents (HMAs) is limited in elderly acute myeloid leukemia (AML) patients. Therefore, combination strategies with targeted therapies are urgently needed. Here, we discover that priming with SGI-110 (guadecitabine), a next-generation HMA, sensitizes AML cells to ASTX660, a novel antagonist of cellular inhibitor of Apoptosis protein 1 and 2 (cIAP1/2) and X-linked IAP (XIAP). Importantly, SGI-110 and ASTX660 synergistically induced cell death in a panel of AML cell lines as well as in primary AML samples while largely sparing normal CD34+ human progenitor cells, underlining the translational relevance of this combination. Unbiased transcriptome analysis revealed that SGI-110 alone or in combination with ASTX660 upregulated the expression of key regulators of both extrinsic and Intrinsic Apoptosis signaling pathways such as TNFRSF10B (DR5), FAS, and BAX. Individual knockdown of the death receptors TNFR1, DR5, and FAS significantly reduced SGI-110/ASTX660-mediated cell death, whereas blocking antibodies for tumor necrosis factor (TNF)-related Apoptosis-inducing ligand (TRAIL) or FAS ligand (FASLG) failed to provide protection. Also, TNFα-blocking antibody Enbrel had little protective effect on SGI-110/ASTX660-induced cell death. Further, SGI-110 and ASTX660 acted in concert to promote cleavage of caspase-8 and BID, thereby providing a link between extrinsic and Intrinsic apoptotic pathways. Consistently, sequential treatment with SGI-110 and ASTX660-triggered loss of mitochondrial membrane potential (MMP) and BAX activation which contributes to cell death, as BAX silencing significantly protected from SGI-110/ASTX660-mediated Apoptosis. Together, these events culminated in the activation of caspases-3/-7, nuclear fragmentation, and cell death. In conclusion, SGI-110 and ASTX660 cooperatively induced Apoptosis in AML cells by engaging extrinsic and Intrinsic Apoptosis pathways, highlighting the therapeutic potential of this combination for AML.
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extrinsic versus Intrinsic Apoptosis pathways in anticancer chemotherapy
Oncogene, 2006Co-Authors: Simone Fulda, Klausmichael DebatiAbstract:Apoptosis or programmed cell death is a key regulator of physiological growth control and regulation of tissue homeostasis. One of the most important advances in cancer research in recent years is the recognition that cell death mostly by Apoptosis is crucially involved in the regulation of tumor formation and also critically determines treatment response. Killing of tumor cells by most anticancer strategies currently used in clinical oncology, for example, chemotherapy, γ-irradiation, suicide gene therapy or immunotherapy, has been linked to activation of Apoptosis signal transduction pathways in cancer cells such as the Intrinsic and/or extrinsic pathway. Thus, failure to undergo Apoptosis may result in treatment resistance. Understanding the molecular events that regulate Apoptosis in response to anticancer chemotherapy, and how cancer cells evade apoptotic death, provides novel opportunities for a more rational approach to develop molecular-targeted therapies for combating cancer.
