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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

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

Author(s): Arijit Kumar Ghosh, Aanchal Verma, Debabrata Majumder, Debasish Maiti, Tathagata Choudhuri, Antara Banerjee and Samiran Saha*

Volume 20, Issue 7, 2024

Published on: 17 January, 2024

Article ID: e170124225746 Pages: 11

DOI: 10.2174/0115734072277726240102062944

Price: $65

Abstract

Aims: To investigate the autophagy-inducing and tumoricidal efficacy of Theaflavins on Ehrlich’s Ascites Carcinoma (EAC) cells.

Background: 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.

Objective: Here, for the first time, the investigation for the anti-tumor efficacy of Theaflavins via autophagy in EAC was attempted.

Methods: 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.

Results: 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.

Conclusion: Theaflavins were efficient inducing autophagy and Type-II PCD in EAC cells. Notably, Theaflavins induced autophagy prior to apoptosis in vitro.

Graphical Abstract


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