المؤلفون: Chou, Ting-Fang, Chuang, Ya-Ting, Hsieh, Wan-Chen, Chang, Pei-Yun, Liu, Hsin-Yu, Mo, Shu-Ting, Hsu, Tzu-Sheng, Miaw, Shi-Chuen, Chen, Ruey-Hwa, Kimchi, Adi, Lai, Ming-Zong

المصدر: Nature Communications ; volume 7, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: Death-associated protein kinase (DAPK) is a tumour suppressor. Here we show that DAPK also inhibits T helper 17 (Th17) and prevents Th17-mediated pathology in a mouse model of autoimmunity. We demonstrate that DAPK specifically downregulates hypoxia-inducible factor 1α (HIF-1α). In contrast to the predominant nuclear localization of HIF-1α in many cell types, HIF-1α is located in both the cytoplasm and nucleus in T cells, allowing for a cytosolic DAPK–HIF-1α interaction. DAPK also binds prolyl hydroxylase domain protein 2 (PHD2) and increases HIF-1α-PHD2 association. DAPK thereby promotes the proline hydroxylation and proteasome degradation of HIF-1α. Consequently, DAPK deficiency leads to excess HIF-1α accumulation, enhanced IL-17 expression and exacerbated experimental autoimmune encephalomyelitis. Additional knockout of HIF-1α restores the normal differentiation of Dapk −/− Th17 cells and prevents experimental autoimmune encephalomyelitis development. Our results reveal a mechanism involving DAPK-mediated degradation of cytoplasmic HIF-1α, and suggest that raising DAPK levels could be used for treatment of Th17-associated inflammatory diseases.

الإتاحة: https://doi.org/10.1038/ncomms11904Test
https://www.nature.com/articles/ncomms11904.pdfTest
https://www.nature.com/articles/ncomms11904Test

المؤلفون: Ko, Li-Wei, Shih, Yi-Cheng, Chikara, Rupesh Kumar, Chuang, Ya-Ting, Chang, Erik C.

المساهمون: Ministry of Science and Technology, Taiwan

المصدر: Frontiers in Human Neuroscience ; volume 10 ; ISSN 1662-5161

مصطلحات موضوعية: Behavioral Neuroscience, Biological Psychiatry, Psychiatry and Mental health, Neurology, Neuropsychology and Physiological Psychology

الإتاحة: https://doi.org/10.3389/fnhum.2016.00185Test

المؤلفون: Tang, Jen-Yang^1,2 (AUTHOR), Chuang, Ya-Ting³ (AUTHOR), Shiau, Jun-Ping⁴ (AUTHOR), Yang, Kun-Han⁵ (AUTHOR), Chang, Fang-Rong⁵ (AUTHOR), Hou, Ming-Feng^4,6 (AUTHOR), Farooqi, Ammad Ahmad⁷ (AUTHOR) farooqiammadahmad@gmail.com, Chang, Hsueh-Wei^6,8 (AUTHOR) farooqiammadahmad@gmail.com

المصدر: Cells (2073-4409). Oct2022, Vol. 11 Issue 19, p2940. 41p.

مصطلحات موضوعية: *LINCRNA, *CELL physiology, *CIRCULAR RNA, *CELL migration, *CANCER cells, *CELLULAR control mechanisms

مستخلص: AKT serine-threonine kinase (AKT) and its effectors are essential for maintaining cell proliferation, apoptosis, autophagy, endoplasmic reticulum (ER) stress, mitochondrial morphogenesis (fission/fusion), ferroptosis, necroptosis, DNA damage response (damage and repair), senescence, and migration of cancer cells. Several lncRNAs and circRNAs also regulate the expression of these functions by numerous pathways. However, the impact on cell functions by lncRNAs and circRNAs regulating AKT and its effectors is poorly understood. This review provides comprehensive information about the relationship of lncRNAs and circRNAs with AKT on the cell functions of cancer cells. the roles of several lncRNAs and circRNAs acting on AKT effectors, such as FOXO, mTORC1/2, S6K1/2, 4EBP1, SREBP, and HIF are explored. To further validate the relationship between AKT, AKT effectors, lncRNAs, and circRNAs, more predicted AKT- and AKT effector-targeting lncRNAs and circRNAs were retrieved from the LncTarD and circBase databases. Consistently, using an in-depth literature survey, these AKT- and AKT effector-targeting database lncRNAs and circRNAs were related to cell functions. Therefore, some lncRNAs and circRNAs can regulate several cell functions through modulating AKT and AKT effectors. This review provides insights into a comprehensive network of AKT and AKT effectors connecting to lncRNAs and circRNAs in the regulation of cancer cell functions. [ABSTRACT FROM AUTHOR]

المؤلفون: Shiau, Jun-Ping, Chuang, Ya-Ting, Tang, Jen-Yang, Chen, Shu-Rong, Hou, Ming-Feng, Jeng, Jiiang-Huei, Cheng, Yuan-Bin, Chang, Hsueh-Wei

المصدر: Antioxidants; Oct2022, Vol. 11 Issue 10, pN.PAG-N.PAG, 21p

مصطلحات موضوعية: ORAL cancer, DOUBLE-strand DNA breaks, CANCER cell proliferation, INHIBITION of cellular proliferation, ORAL mucosa, DNA damage, CANCER cells

مستخلص: The purpose of this study aimed to assess the antiproliferation effects of methanol extract of T. swinhoei (METS) and explore the detailed responses of oral cancer cells compared to normal cells. METS effectively inhibits the cell proliferation of oral cancer cells but does not affect normal cell viability, exhibiting preferential antiproliferation function. METS exerted more subG1 accumulation, apoptosis induction, cellular and mitochondrial oxidative stress, and DNA damage than normal cells, reverted by oxidative stress inhibitor N-acetylcysteine. This METS-caused oxidative stress was validated to attribute to the downregulation of glutathione. METS activated both extrinsic and intrinsic caspases. DNA double-strand breaks (γH2AX) and oxidative DNA damage (8-hydroxy-2-deoxyguanosine) were stimulated by METS. Therefore, for the first time, this investigation shed light on exploring the functions and responses of preferential antiproliferation of METS in oral cancer cells. [ABSTRACT FROM AUTHOR]

: Copyright of Antioxidants is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Shiau, Jun-Ping, Chuang, Ya-Ting, Tang, Jen-Yang, Yang, Kun-Han, Chang, Fang-Rong, Hou, Ming-Feng, Yen, Ching-Yu, Chang, Hsueh-Wei

المصدر: Antioxidants; Sep2022, Vol. 11 Issue 9, p1845-1845, 46p

مصطلحات موضوعية: CELL physiology, OXIDATIVE stress, NATURAL products, ENDOPLASMIC reticulum, DNA damage, CANCER cells, ANTINEOPLASTIC agents

مستخلص: Oxidative stress and AKT serine-threonine kinase (AKT) are responsible for regulating several cell functions of cancer cells. Several natural products modulate both oxidative stress and AKT for anticancer effects. However, the impact of natural product-modulating oxidative stress and AKT on cell functions lacks systemic understanding. Notably, the contribution of regulating cell functions by AKT downstream effectors is not yet well integrated. This review explores the role of oxidative stress and AKT pathway (AKT/AKT effectors) on ten cell functions, including apoptosis, autophagy, endoplasmic reticulum stress, mitochondrial morphogenesis, ferroptosis, necroptosis, DNA damage response, senescence, migration, and cell-cycle progression. The impact of oxidative stress and AKT are connected to these cell functions through cell function mediators. Moreover, the AKT effectors related to cell functions are integrated. Based on this rationale, natural products with the modulating abilities for oxidative stress and AKT pathway exhibit the potential to regulate these cell functions, but some were rarely reported, particularly for AKT effectors. This review sheds light on understanding the roles of oxidative stress and AKT pathway in regulating cell functions, providing future directions for natural products in cancer treatment. [ABSTRACT FROM AUTHOR]

: Copyright of Antioxidants is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Liu, Wangta, Hsu, Yin-Yin, Tang, Jen-Yang, Cheng, Yuan-Bin, Chuang, Ya-Ting, Jeng, Jiiang-Huei, Yen, Chia-Hung, Chang, Hsueh-Wei

المصدر: Antioxidants; Sep2022, Vol. 11 Issue 9, p1813-1813, 19p

مصطلحات موضوعية: CANCER cell proliferation, ORAL cancer, CANCER cell culture, PLANT extracts, CANCER cells, ORAL mucosa, DNA damage, CASPASES

مستخلص: Data regarding the effects of crude extract of Commelina plants in oral cancer treatment are scarce. This present study aimed to assess the proliferation-modulating effects of the Commelina sp. (MECO) methanol extract on oral cancer cells in culture, Ca9-22, and CAL 27. MECO suppressed viability to a greater extent in oral cancer cells than in normal cells. MECO also induced more annexin V, apoptosis, and caspase signaling for caspases 3/8/9 in oral cancer cells. The preferential antiproliferation and apoptosis were associated with cellular and mitochondrial oxidative stress in oral cancer cells. Moreover, MECO also preferentially induced DNA damage in oral cancer cells by elevating γH2AX and 8-hydroxyl-2′-deoxyguanosine. The oxidative stress scavengers N-acetylcysteine or MitoTEMPO reverted these preferential antiproliferation mechanisms. It can be concluded that MECO is a natural product with preferential antiproliferation effects and exhibits an oxidative stress-associated mechanism in oral cancer cells. [ABSTRACT FROM AUTHOR]

: Copyright of Antioxidants is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Chuang, Ya-Ting, Shiau, Jun-Ping, Yen, Ching-Yu, Hou, Ming-Feng, Jeng, Jiiang-Huei, Tang, Jen-Yang, Chang, Hsueh-Wei

المصدر: Antioxidants; Sep2022, Vol. 11 Issue 9, p1797-1797, 18p

مصطلحات موضوعية: ORAL cancer, CANCER cells, ORAL mucosa, REACTIVE oxygen species, ANNEXINS, POLYSACCHARIDES, REACTIVE flow

مستخلص: Combined treatment is a promising anticancer strategy for improving antiproliferation compared with a single treatment but is limited by adverse side effects on normal cells. Fucoidan (FN), a brown-algae-derived polysaccharide safe food ingredient, exhibits preferential function for antiproliferation to oral cancer but not normal cells. Utilizing the preferential antiproliferation, the impacts of FN in regulating ultraviolet C (UVC) irradiation were assessed in oral cancer cells. A combined treatment (UVC/FN) reduced cell viability of oral cancer cells (Ca9-22 and CAL 27) more than single treatments (FN or UVC), i.e., 53.7%/54.6% vs. 71.2%/91.6%, and 89.2%/79.4%, respectively, while the cell viability of UVC/FN treating on non-malignant oral (S–G) was higher than oral cancer cells, ranging from 106.0 to 108.5%. Mechanistically, UVC/FN preferentially generated higher subG1 accumulation and apoptosis-related inductions (annexin V, caspases 3, 8, and 9) in oral cancer cells than single treatments. UVC/FN preferentially generated higher oxidative stress than single treatments, as evidenced by flow cytometry-detecting reactive oxygen species, mitochondrial superoxide, and glutathione. Moreover, UVC/FN preferentially caused more DNA damage (γH2AX and 8-hydroxy-2'-deoxyguanosine) in oral cancer cells than in single treatments. N-acetylcysteine pretreatment validated the oxidative stress effects in these UVC/FN-induced changes. Taken together, FN effectively enhances UVC-triggered antiproliferation to oral cancer cells. UVC/FN provides a promising potential for preferential and synergistic antiproliferation in antioral cancer therapy. [ABSTRACT FROM AUTHOR]

: Copyright of Antioxidants is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Hsu, Yin-Yin, Chuang, Ya-Ting, Yen, Ching-Yu, Cheng, Ming-Ya, Chen, Ching-Yeu, Cheng, Yuan-Bin, Chang, Hsueh-Wei

المصدر: Antioxidants; Sep2022, Vol. 11 Issue 9, p1777-1777, 18p

مصطلحات موضوعية: ORAL cancer, DNA damage, MARINE natural products, CANCER cells, ORAL mucosa, REACTIVE oxygen species, APOPTOSIS, ANNEXINS

مستخلص: Antiproliferation effects of Clavularia-derived natural products against cancer cells have been reported on, but most studies have focused on identifying bioactive compounds, lacking a detailed investigation of the molecular mechanism. Crude extracts generally exhibit multiple targeting potentials for anticancer effects, but they have rarely been assessed for methanol extracts of Clavularia inflata (MECI). This investigation aims to evaluate the antiproliferation of MECI and to examine several potential mechanisms between oral cancer and normal cells. A 24 h MTS assay demonstrated that MECI decreased cell viability in several oral cancer cell lines more than in normal cells. N-acetylcysteine (NAC), an oxidative stress inhibitor, recovered these antiproliferation effects. Higher oxidative stress was stimulated by MECI in oral cancer cells than in normal cells, as proven by examining reactive oxygen species and mitochondrial superoxide. This preferential induction of oxidative stress was partly explained by downregulating more cellular antioxidants, such as glutathione, in oral cancer cells than in normal cells. Consequently, the MECI-generated high oxidative stress in oral cancer cells was preferred to trigger more subG1 population, apoptosis expression (annexin V and caspase activation), and DNA damage, reverted by NAC. In conclusion, MECI is a potent marine natural product showing preferential antiproliferation against oral cancer cells. [ABSTRACT FROM AUTHOR]

: Copyright of Antioxidants is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Shiau, Jun-Ping, Chuang, Ya-Ting, Cheng, Yuan-Bin, Tang, Jen-Yang, Hou, Ming-Feng, Yen, Ching-Yu, Chang, Hsueh-Wei

المصدر: Antioxidants; May2022, Vol. 11 Issue 5, p911, 17p

مصطلحات موضوعية: OXIDATIVE stress, KREBS cycle, PENTOSE phosphate pathway, METABOLIC regulation, GLYCOLYSIS, CELL metabolism, METABOLISM

مستخلص: The critical factors for regulating cancer metabolism are oxidative stress and phosphoinositide-3-kinase/AKT serine-threonine kinase/mechanistic target of the rapamycin kinase (PI3K/AKT/mTOR). However, the metabolic impacts of oxidative stress and PI3K/AKT/mTOR on individual mechanisms such as glycolysis (Warburg effect), pentose phosphate pathway (PPP), fatty acid synthesis, tricarboxylic acid cycle (TCA) cycle, glutaminolysis, and oxidative phosphorylation (OXPHOS) are complicated. Therefore, this review summarizes the individual and interacting functions of oxidative stress and PI3K/AKT/mTOR on metabolism. Moreover, natural products providing oxidative stress and PI3K/AKT/mTOR modulating effects have anticancer potential. Using the example of brown algae-derived fucoidan, the roles of oxidative stress and PI3K/AKT/mTOR were summarized, although their potential functions within diverse metabolisms were rarely investigated. We propose a potential application that fucoidan may regulate oxidative stress and PI3K/AKT/mTOR signaling to modulate their associated metabolic regulations. This review sheds light on understanding the impacts of oxidative stress and PI3K/AKT/mTOR on metabolism and the future direction of metabolism-based cancer therapy of fucoidan. [ABSTRACT FROM AUTHOR]

: Copyright of Antioxidants is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Shiau, Jun-Ping, Chuang, Ya-Ting, Yang, Kun-Han, Chang, Fang-Rong, Sheu, Jyh-Horng, Hou, Ming-Feng, Jeng, Jiiang-Huei, Tang, Jen-Yang, Chang, Hsueh-Wei

المصدر: Antioxidants; May2022, Vol. 11 Issue 5, p841, 21p

مصطلحات موضوعية: ORAL cancer, CANCER cells, ORAL mucosa, REACTIVE oxygen species, POLYSACCHARIDES

مستخلص: Fucoidan is a dietary brown algae-derived fucose-rich polysaccharide. However, the anticancer effects of fucoidan for oral cancer treatment remain unclear, particularly in terms of its preferential antiproliferation ability and oxidative-stress-associated responses. This study first evaluated the effects and mechanisms of the preferential antiproliferation of fucoidan between oral cancer and non-malignant oral cells (S–G). In a 48 h MTS assay, fucoidan showed higher antiproliferation in response to five types of oral cancer cells, but not S–G cells, demonstrating preferential antiproliferation of oral cancer cells. Oral cancer cells (Ca9-22 and CAL 27) showing high sensitivity to fucoidan were selected to explore the antiproliferation mechanism compared to S–G cells. Fucoidan showed subG1 accumulation and an annexin V increase in apoptosis, accompanied by caspase 8, 9, and 3 activations in oral cancer cells, but not in S–G cells. Fucoidan increased reactive oxygen species and mitochondrial superoxide levels and decreased cellular glutathione in oral cancer cells compared with S–G cells. These oxidative stress effects were attributed to the downregulation of antioxidant signaling genes (NRF2, TXN, and HMOX1) in oral cancer cells rather than S–G cells. Fucoidan showed DNA damage-inducible effects (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer cells but not in S–G cells. Accordingly, these preferential changes in oral cancer but not in non-malignant cells contribute to the preferential antiproliferation mechanism of fucoidan. Furthermore, these changes were reverted by pretreatment with the antioxidant N-acetylcysteine. Therefore, for the first time, this study provides a detailed understanding of the preferential antiproliferation effects and mechanisms of fucoidan in oral cancer cells. [ABSTRACT FROM AUTHOR]

: Copyright of Antioxidants is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)