Chemopreventive effect of caffeine on arsenite-induced carcinogenesis in lung cancer cells via suppression of p53 and heme oxygenase-1

• Published in: Biotechnology and bioprocess engineering Vol. 30; no. 1; pp. 42 - 54
• Main Authors: Kim, Sang-Hun, Oh, Seon-Hee
• Format: Journal Article
• Language: English
• Published: Seoul The Korean Society for Biotechnology and Bioengineering 01.02.2025; Springer Nature B.V; 한국생물공학회
• Subjects: Acetylcysteine; Actinomycin; Apoptosis; Arsenic; Arsenite; arsenites; Ataxia; Ataxia telangiectasia; Biotechnology; Caffeine; Carcinogenesis; Carcinogens; Caspase-3; Cell cycle; Chemistry; Chemistry and Materials Science; chemoprevention; CHK1 protein; Cycloheximide; Cytotoxicity; Degradation; fluorescence; heme oxygenase (biliverdin-producing); Heme oxygenase (decyclizing); human health; Industrial and Production Engineering; Lung cancer; lung neoplasms; MAP kinase; mitogen-activated protein kinase; p53 Protein; Poly(ADP-ribose) polymerase; Proteins; radio; Research Paper; S phase; Sodium arsenite; Therapeutic targets; therapeutics; Western blotting; 생물공학; Cell cycle checkpoint response; Caspase-3; Arsenite; Heme oxygenase-1; Caffeine
• ISSN: 1226-8372; 1976-3816
• DOI: 10.1007/s12257-025-00182-1

Caffeine is a radio and chemosensitizer; however, its role in chemoprevention remains unknown. Arsenic is a potent carcinogen that threatens human health. Here, we investigated the effects of caffeine on arsenite (NaAsO 2 )-induced carcinogenesis. Cytotoxicity was assessed by 2,5-diphenyl-2H-tetrazolium bromide assay and confirmed by morphological observation and fluorescence staining. Cell cycle progression- and apoptosis-related proteins were analyzed by Western blotting. Nuclear factor erythroid2-related factor 2 (NRF2) overexpression was used to confirm the biological function of heme oxygenase-1 (HO-1). NaAsO 2 treatment of A549 (p53 + / +) cells increased the levels of p-ataxia telangiectasia and Rad3-related, p-Chk1, p-Cdc2 Thr161 , and p53, which were reduced by caffeine. Caffeine also induced procaspase-3 and HO-1 protein reduction and PARP-1 degradation in a concentration-dependent manner, with similar effects in NaAsO 2 -treated cells. The effects of caffeine were reversed by N -acetyl-L-cysteine treatment, which also inhibited JNK and p38 MAPK activation. The increase in HO-1-mediated by NRF2 overexpression inhibited procaspase-3 and PARP-1 degradation and partially upregulated p53 and p21 levels. Treatment with cycloheximide or actinomycin D further reduced caffeine-mediated HO-1, procaspase-3, and PARP-1 degradation. Caffeine increased chemosensitivity to NaAsO 2 by inducing NaAsO 2 -induced G1-S phase checkpoint response inhibition and apoptosis through genetic regulation of HO-1. These findings suggest that HO-1 may be an important therapeutic target to overcome NaAsO 2 -induced carcinogenesis.