Caffeic acid and protocatechuic acid modulate Nrf2 and inhibit Ehrlich ascites carcinomas in mice

Venugopal Bovilla; Preethi Anantharaju; Prashanthkumar Veeresh; Mahadevaswamy Kuruburu; Vidya Bettada; Subbarao Madhunapantula; Sireesh Dornadula; Kunka Ramkumar

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Caffeic acid and protocatechuic acid modulate Nrf2 and inhibit Ehrlich ascites carcinomas in mice

Author: Venugopal BOVILLA ¹ ; Preethi ANANTHARAJU ¹ ; Prashanthkumar VEERESH ¹ ; Mahadevaswamy KURUBURU ¹ ; Vidya BETTADA ¹ ; Subbarao MADHUNAPANTULA ¹ ; Sireesh DORNADULA ² ; Kunka RAMKUMAR ²
Author Information

1. Center of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research
2. SRM Research Institute, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology
Publication Type:Journal Article
Keywords: Caffeic acid; Ehrlich ascites carcinomas; NQO1 activity; Nrf2; Protocatechuic acid
From:Asian Pacific Journal of Tropical Biomedicine 2021;11(6):244-253
CountryChina
Language:Chinese
Abstract: Objective: To assess the nuclear factor-erythroid 2-related factor-2 (Nrf2) modulatory effect of caffeic acid and protocatechuic acid and determine the anti-tumor activity of these phenolic compounds against Ehrlich ascites carcinoma growth in mice. Methods: Antioxidant activity of protocatechuic acid and caffeic acid was assessed using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). Nrf2 activation potential of phenolic compounds was tested by quantitative realtime polymerase chain reaction, and luciferase complementation reporter assays. In vivo efficacy was tested using the Ehrlich ascites carcinoma model. Results: FRAP and DPPH radical scavenging assays showed that caffeic acid and protocatechuic acid were more potent compared with cinnamic acid and benzoic acid. Luciferase complementation reporter assays identified caffeic acid and protocatechuic acid as the activators of Nrf2. Both caffeic acid and protocatechuic acid upregulated the expression of Nrf2 target genes heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) and the activity of NAD(P)H:quinone oxidoreductase 1 (NQO1) when tested on HCT-116 cells using a cell-based assay system at 9 h. In addition, intraperitoneal administration of caffeic acid and protocatechuic acid to Ehrlich ascites carcinoma bearing mice suppressed tumor growth and angiogenesis. Conclusions: Caffeic acid and protocatechuic acid can modulate Nrf2 and inhibit Ehrlich ascites carcinoma cells.