Tetrahydrobiopterin from cyanide-degrading bacterium Bacillus pumilus strain SVD06 induces apoptosis in human lung adenocarcinoma cell (A549).
Ramasamy MahendranSanjay Prasad SelvarajAnand Raj DhanapalSabna Bhaskaran SarasaBeutline Malgija MathiasBency ThankappanDaniel Raja Femil SeltaPalanivel NaveenRhenghachar PooraniNavaneethan SundharMamatha M PillaiRajendran SelvakumarChih-Yang HuangRaju EswaranAngayarkanni JayaramanPublished in: Biotechnology and applied biochemistry (2023)
Tetrahydrobiopterin (BH4) is an essential biological cofactor and a derivative of pterin which is considered potent anticancer agents. In continuation of our previous study on the identification of BH4 from cyanide-degrading Bacillus pumilus, the present study focuses on evaluating the anticancer properties of BH4 on A549, a human lung adenocarcinoma. Anticancer activity analysis shows that BH4 inhibited A549 cell growth after 24 h of incubation with 0.02 mg/mL. In acridine orange/ethidium bromide staining, BH4-treated A549 cells showed apoptotic morphology. BH4 treatment caused cell cycle arrest at G0/G1 phase compared to control cells. BH4 augmented p53 expression in alveolar cancer cells by downregulating MDM2 levels. There was downregulation of casp-3 and upregulation of iNOS gene in BH4-treated A549 cells. Further, docking studies indicated that BH4 had significant interactions with the above proteins affirming the apoptosis mechanism. Thus, BH4 could be considered a potential anticancer drug.
Keyphrases
- cell cycle arrest
- cell death
- pi k akt
- induced apoptosis
- signaling pathway
- endothelial cells
- endoplasmic reticulum stress
- cell proliferation
- poor prognosis
- emergency department
- dna methylation
- stem cells
- risk assessment
- copy number
- climate change
- small molecule
- transcription factor
- molecular dynamics
- electronic health record
- cell therapy
- replacement therapy
- human health