Theaflavins Induce Autophagy in Ehrlich’s Ascites Carcinoma Cells both In vivo and In vitro

Q2 Pharmacology, Toxicology and Pharmaceutics
Arijit Kumar Ghosh, Aanchal Verma, Debabrata Majumder, Debasish Maiti, Tathagata Choudhuri, Antara Banerjee, Samiran Saha
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引用次数: 0

Abstract

To investigate the efficacy of Theaflavins to induce autophagy and its tumoricidal activity towards Ehrlich’s Ascites Carcinoma cells. The apoptosis-inducing role of Theaflavins against cancer is reported. Autophagy, a cellular mechanism under stress, occurs either as a survival process or Type-II programmed-cell death in the presence/absence of apoptosis. The report of Theaflavins inducing autophagy against cancer is poor. Here, for the first time, the investigation for the anti-tumor efficacy of Theaflavins via autophagy in EAC was attempted. EAC-bearing mice were treated orally with Theaflavins (10 mg/kg b.w.) every alternate day with a total of 27 doses. Body weight, tumor volume and survivability were recorded. Tumoricidal and cellular dehydrogenase activity, in vivo and in vitro, were studied using Trypan-blue exclusion and MTT assay respectively. Theaflavins-treated EAC cells were subjected to Monodansylcadaverine- staining. LC3II turnover and LC3I conversion were detected by western blotting. Apoptosis up to 12 h TF-treatment was estimated by AnnexinV binding. This is the first report of Theaflavins inducing autophagy in EAC cells in vivo and in vitro. Oral Theaflavins treatment restricted excessive body-weight increase due to tumors, reduced tumor volume, and increased survivability of tumor-bearing mice. Theaflavins caused EAC cell death (~8% in vitro, ~30% in vivo), significantly reduced metabolic activity, and created conspicuous vacuolization in surviving cells. Resultant vacuoles (in vitro, 6 h) were marked as autophagosomes by Monodansylcadaverine-staining. Autophagy was confirmed by LC3II augmentation. No significant apoptosis was observed up to 12 h TF-treatment in vitro. Theaflavins were efficient inducing autophagy and Type-II PCD in EAC cells. Notably, Theaflavins induced autophagy prior to apoptosis in vitro.
茶黄素在体内和体外都能诱导艾氏腹水癌细胞自噬
目的:研究茶黄素诱导自噬的功效及其对艾氏腹水癌细胞的杀瘤活性。自噬是压力下的一种细胞机制,在存在或不存在细胞凋亡的情况下,它可以作为一种生存过程或第二类程序性细胞死亡而发生。本文首次尝试研究茶黄素通过自噬作用对 EAC 的抗肿瘤疗效。记录体重、肿瘤体积和存活率。使用胰蓝排除法和 MTT 法分别研究了体内和体外的杀瘤活性和细胞脱氢酶活性。对经茶黄素处理的 EAC 细胞进行单丹酮金刚烷染色。这是首次报道茶黄素诱导EAC细胞体内和体外自噬。口服茶黄素可抑制肿瘤导致的体重过度增加,减少肿瘤体积,提高肿瘤小鼠的存活率。茶黄素会导致 EAC 细胞死亡(体外约为 8%,体内约为 30%),显著降低代谢活性,并在存活细胞中产生明显的空泡化。结果产生的空泡(体外,6 小时)通过 Monodansylcadaverine 染色被标记为自噬体。体外 TF 处理 12 h 内未观察到明显的细胞凋亡。值得注意的是,茶黄素能在体外诱导细胞凋亡前诱导自噬。
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来源期刊
Current Bioactive Compounds
Current Bioactive Compounds Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
1.90
自引率
0.00%
发文量
112
期刊介绍: The journal aims to provide comprehensive review articles on new bioactive compounds with proven activities in various biological screenings and pharmacological models with a special emphasis on stereoeselective synthesis. The aim is to provide a valuable information source of bioactive compounds synthesized or isolated, which can be used for further development of pharmaceuticals by industry and academia. The journal should prove to be essential reading for pharmacologists, natural product chemists and medicinal chemists who wish to be kept informed and up-to-date with the most important developments on new bioactive compounds of natural or synthetic origin, including their stereoeselective synthesis.
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