Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Gallic Acid Hindered Lung Cancer Progression by Inducing Cell Cycle Arrest and Apoptosis in A549 Lung Cancer Cells via PI3K/Akt Pathway

  • Ko, Eul-Bee (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Jang, Yin-Gi (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Kim, Cho-Won (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Go, Ryeo-Eun (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Lee, Hong Kyu (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Choi, Kyung-Chul (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
  • Received : 2021.04.19
  • Accepted : 2021.06.30
  • Published : 2022.03.01
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Abstract

This study elucidates the anti-cancer potential of gallic acid (GA) as a promising therapeutic agent that exerts its effect by regulating the PI3K/Akt pathway. To prove our research rationale, we used diverse experimental methods such as cell viability assay, colony formation assay, tumor spheroid formation assay, cell cycle analysis, TUNEL assay, Western blot analysis, xenograft mouse model and histological analysis. Treatment with GA inhibited cell proliferation in dose-dependent manner as measured by cell viability assay at 48 h. GA and cisplatin (CDDP) also inhibited colony formation and tumor spheroid formation. In addition, GA and CDDP induced apoptosis, as determined by the distribution of early and late apoptotic cells and DNA fragmentation. Western blot analysis revealed that inhibition of the PI3K/Akt pathway induced upregulation of p53 (tumor suppressor protein), which in turn regulated cell cycle related proteins such as p21, p27, Cyclin D1 and E1, and intrinsic apoptotic proteins such as Bax, Bcl-2 and cleaved caspase-3. The anti-cancer effect of GA was further confirmed in an in vivo mouse model. Intraperitoneal injection with GA for 4 weeks in an A549-derived tumor xenograft model reduced the size of tumor mass. Injection of them downregulated the expression of proliferating cell nuclear antigen and p-Akt, but upregulated the expression of cleaved caspase-3 in tumor tissues. Taken together, these results indicated that GA hindered lung cancer progression by inducing cell cycle arrest and apoptosis, suggesting that GA would be a potential therapeutic agent against non-small cell lung cancer.

Keywords

Acknowledgement

This work was supported by the Basic Science Research Program (2020R1A2C2006060) and the Global Research and Development Center (GRDC) Program (2017K1A4A3014959) through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT. In addition, this work was also supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agriculture, Food and Rural Affairs Convergence Technologies Program for Educating Creative Global Leader, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA; grant number: 320005-4).

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