We are analyzing https://link.springer.com/article/10.1007/s11010-020-03699-6.

Title:
Arctigenin induces necroptosis through mitochondrial dysfunction with CCN1 upregulation in prostate cancer cells under lactic acidosis | Molecular and Cellular Biochemistry
Description:
Arctigenin, a mitochondrial complex I inhibitor, has been identified as a potential anti-tumor agent, but the involved mechanism still remains elusive. Herein, we studied the underlying mechanism(s) of action of arctigenin on acidity-tolerant prostate cancer PC-3AcT cells in the lactic acid-containing medium. At concentration showing no toxicity on normal prostate epithelial RWPE-1 and HPrEC cells, arctigenin alone or in combination with docetaxel induced significant cytotoxicity in PC-3AcT cells compared to parental PC-3 cells. With arctigenin treatment, reactive oxygen species (ROS) levels, annexin V-PE positive fractions, sub-G0/G1 peak in cell cycle analysis, mitochondrial membrane depolarization, and cell communication network factor 1 (CCN1) levels were increased, while cellular ATP content and phospho (p)-Akt level were decreased. Pretreatment with ROS scavenger N-acetylcysteine effectively reversed the series of phenomena caused by arctigenin, suggesting that ROS served as upstream molecules of arctigenin-driven cytotoxicity. Meanwhile, arctigenin increased the levels of p-receptor-interacting serine/threonine-protein kinase 3 (p-RIP3) and p-mixed lineage kinase domain-like pseudokinase (p-MLKL) as necroptosis mediators, and pretreatment with necroptosis inhibitor necrostatin-1 restored their levels and cell viability. Treatment of spheroids with arctigenin resulted in necroptotic cell death, which was prevented by N-acetylcysteine. The siRNA-based knockdown of CCN1 suppressed the levels of MLKL, B-cell lymphoma 2 (Bcl-2), and induced myeloid leukemia cell differentiation (Mcl-1) with increased cleavage of Bcl-2-associated X (Bax) and caspase-3. Collectively, these results provide new insights into the molecular mechanisms underlying arctigenin-induced cytotoxicity, and support arctigenin as a potential therapeutic agent for targeting non-Warburg phenotype through induction of necroptosis via ROS-mediated mitochondrial damage and CCN1 upregulation.
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article, google, scholar, cell, arctigenin, cas, cancer, cells, prostate, ccn, lee, necroptosis, death, research, content, mitochondrial, cytotoxicity, apoptosis, biochem, privacy, cookies, molecular, induces, lactic, mechanisms, levels, access, chen, information, publish, search, cellular, acidosis, sanghan, action, increased, oxidative, res, wang, soonchunhyang, springer, data, log, journal, biochemistry, dysfunction, upregulation, published, february, yoonjin,

Topics {✒️}

moon-kyun cho & sang-han lee integrin-mediated matrix signaling reactive oxygen species month download article/chapter sang-han lee high-throughput culture platform pc-3act cells compared arctigenin-induced specific cytotoxicity extracellular matrix–remodeling genes potential anti-tumor agent ros/p38 mapk pathway ros-mediated mitochondrial damage pi3k/akt/mtor pathway dominant oxidative phosphorylation prostate cancer cells necroptotic cell death breast cancer cells parental pc-3 cells lactic acid molecular cancer research lactic acidosis published full article pdf privacy choices/manage cookies arctigenin induces necroptosis anti-cancer therapy colon cancer cells article lee cellular biochemistry aims potential therapeutic agent fas-mediated apoptosis ros/p38mapk pathway necroptosis-inducing effects proinflammatory genetic program national research foundation cellular atp content arctigenin-driven cytotoxicity b-cell lymphoma 2 arctigenin induces apoptosis cell death function lactic acidosis cell cycle analysis european economic area g0/g1 peak sirna-based knockdown double edged sword small-molecule compounds mueller-klieser wf aerobic glycolysis back ameliorates metabolic disorders ob/ob mice

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         headline:Arctigenin induces necroptosis through mitochondrial dysfunction with CCN1 upregulation in prostate cancer cells under lactic acidosis
         description:Arctigenin, a mitochondrial complex I inhibitor, has been identified as a potential anti-tumor agent, but the involved mechanism still remains elusive. Herein, we studied the underlying mechanism(s) of action of arctigenin on acidity-tolerant prostate cancer PC-3AcT cells in the lactic acid-containing medium. At concentration showing no toxicity on normal prostate epithelial RWPE-1 and HPrEC cells, arctigenin alone or in combination with docetaxel induced significant cytotoxicity in PC-3AcT cells compared to parental PC-3 cells. With arctigenin treatment, reactive oxygen species (ROS) levels, annexin V-PE positive fractions, sub-G0/G1 peak in cell cycle analysis, mitochondrial membrane depolarization, and cell communication network factor 1 (CCN1) levels were increased, while cellular ATP content and phospho (p)-Akt level were decreased. Pretreatment with ROS scavenger N-acetylcysteine effectively reversed the series of phenomena caused by arctigenin, suggesting that ROS served as upstream molecules of arctigenin-driven cytotoxicity. Meanwhile, arctigenin increased the levels of p-receptor-interacting serine/threonine-protein kinase 3 (p-RIP3) and p-mixed lineage kinase domain-like pseudokinase (p-MLKL) as necroptosis mediators, and pretreatment with necroptosis inhibitor necrostatin-1 restored their levels and cell viability. Treatment of spheroids with arctigenin resulted in necroptotic cell death, which was prevented by N-acetylcysteine. The siRNA-based knockdown of CCN1 suppressed the levels of MLKL, B-cell lymphoma 2 (Bcl-2), and induced myeloid leukemia cell differentiation (Mcl-1) with increased cleavage of Bcl-2-associated X (Bax) and caspase-3. Collectively, these results provide new insights into the molecular mechanisms underlying arctigenin-induced cytotoxicity, and support arctigenin as a potential therapeutic agent for targeting non-Warburg phenotype through induction of necroptosis via ROS-mediated mitochondrial damage and CCN1 upregulation.
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      headline:Arctigenin induces necroptosis through mitochondrial dysfunction with CCN1 upregulation in prostate cancer cells under lactic acidosis
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         Necroptosis
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         Prostate cancer
         Lactic acid
         Oxidative stress
         Biochemistry
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         Cancer Research
         Medical Biochemistry
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