3 results on '"Changou, Chun A."'
Search Results
2. Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy
- Author
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Changou, Chun A, Chen, Yun-Ru, Xing, Li, Yen, Yun, Chuang, Frank YS, Cheng, R Holland, Bold, Richard J, Ann, David K, and Kung, Hsing-Jien
- Subjects
Male ,Urologic Diseases ,Nuclear Envelope ,Hydrolases ,1.1 Normal biological development and functioning ,Antineoplastic Agents ,Argininosuccinate Synthase ,Arginine ,Electron ,Membrane Potential ,Cell Line ,Polyethylene Glycols ,Underpinning research ,Autophagy ,Genetics ,Humans ,Transmission ,2.1 Biological and endogenous factors ,Aetiology ,ADI-PEG20 ,arginine auxotrophy ,Cancer ,Microscopy ,Tumor ,Cell Death ,Prostate Cancer ,Prostatic Neoplasms ,DNA ,Chromatin ,Mitochondria ,Mitochondrial ,Neoplasm ,cancer therapy ,metabolic stress ,Generic health relevance ,Reactive Oxygen Species - Abstract
Autophagy is the principal catabolic prosurvival pathway during nutritional starvation. However, excessive autophagy could be cytotoxic, contributing to cell death, but its mechanism remains elusive. Arginine starvation has emerged as a potential therapy for several types of cancers, owing to their tumor-selective deficiency of the arginine metabolism. We demonstrated here that arginine depletion by arginine deiminase induces a cytotoxic autophagy in argininosuccinate synthetase (ASS1)-deficient prostate cancer cells. Advanced microscopic analyses of arginine-deprived dying cells revealed a novel phenotype with giant autophagosome formation, nucleus membrane rupture, and histone-associated DNA leakage encaptured by autophagosomes, which we shall refer to as chromatin autophagy, or chromatophagy. In addition, nuclear inner membrane (lamin A/C) underwent localized rearrangement and outer membrane (NUP98) partially fused with autophagosome membrane. Further analysis showed that prolonged arginine depletion impaired mitochondrial oxidative phosphorylation function and depolarized mitochondrial membrane potential. Thus, reactive oxygen species (ROS) production significantly increased in both cytosolic and mitochondrial fractions, presumably leading to DNA damage accumulation. Addition of ROS scavenger N-acetyl cysteine or knockdown of ATG5 or BECLIN1 attenuated the chromatophagy phenotype. Our data uncover an atypical autophagy-related death pathway and suggest that mitochondrial damage is central to linking arginine starvation and chromatophagy in two distinct cellular compartments.
- Published
- 2014
3. Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer
- Author
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Ya Jung Shih, Yu Tang Chin, Wen Shan Li, Hung Yun Lin, James A. Bennett, Earl Fu, Leroy F. Liu, Jens Z. Pedersen, Chi-Yu Lin, Sandra Incerpi, Chun A. Changou, Jacqueline Whang-Peng, Shaker A. Mousa, Paul J. Davis, André Wendindondé Nana, Yih Ho, Yi Ru Chen, Nana, André Wendindondé, Chin, Yu-Tang, Lin, Chi-Yu, Ho, Yih, Bennett, James A, Shih, Ya-Jung, Chen, Yi-Ru, Changou, Chun A, Pedersen, Jens Z, Incerpi, Sandra, Liu, Leroy F, Whang-Peng, Jacqueline, Fu, Earl, Li, Wen-Shan, Mousa, Shaker A, Lin, Hung-Yun, and Davis, Paul J
- Subjects
0301 basic medicine ,Cancer Research ,Beta-catenin ,HMGA2 ,Endocrinology, Diabetes and Metabolism ,Down-Regulation ,Mice, Nude ,colorectal cancer ,Antineoplastic Agents ,Resveratrol ,resveratrol ,Settore BIO/09 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Cell Line, Tumor ,Animals ,Humans ,tetraiodothyroacetic acid ,beta Catenin ,Cell Proliferation ,biology ,Cell growth ,HMGA2 Protein ,Wnt signaling pathway ,Drug Synergism ,β-catenin ,colorectal cancers ,Gene Expression Regulation, Neoplastic ,Thyroxine ,030104 developmental biology ,Oncology ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,Catenin ,Cancer cell ,Colonic Neoplasms ,biology.protein ,Cancer research ,Female - Abstract
The molecular pathogenesis of colorectal cancer encompasses the activation of several oncogenic signaling pathways that include the Wnt/β-catenin pathway and the overexpression of high mobility group protein A2 (HMGA2). Resveratrol – the polyphenolic phytoalexin – binds to integrin αvβ3 to induce apoptosis in cancer cellsviacyclooxygenase 2 (COX-2) nuclear accumulation and p53-dependent apoptosis. Tetraiodothyroacetic acid (tetrac) is a de-aminated derivative ofl-thyroxine (T4), which – in contrast to the parental hormone – impairs cancer cell proliferation. In the current study, we found that tetrac promoted resveratrol-induced anti-proliferation in colon cancer cell lines, in primary cultures of colon cancer cells, andin vivo. The mechanisms implicated in this action involved the downregulation of nuclear β-catenin and HMGA2, which are capable of compromising resveratrol-induced COX-2 nuclear translocation. Silencing of either β-catenin or HMGA2 promoted resveratrol-induced anti-proliferation and COX-2 nuclear accumulation which is essential for integrin αvβ3-mediated-resveratrol-induced apoptosis in cancer cells. Concurrently, tetrac enhanced nuclear abundance of chibby family member 1, the nuclear β-catenin antagonist, which may further compromise the nuclear β-catenin-dependent gene expression and proliferation. Taken together, these results suggest that tetrac targets β-catenin and HMGA2 to promote resveratrol-induced-anti-proliferation in colon cancers, highlighting its potential in anti-cancer combination therapy.
- Published
- 2017
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