ABSTRACT
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.
Subject(s)
Adenocarcinoma of Lung , Antineoplastic Agents , Bacillus pumilus , Lung Neoplasms , Humans , Cyanides/pharmacology , Cyanides/therapeutic use , Cell Line, Tumor , Adenocarcinoma of Lung/drug therapy , Apoptosis , Antineoplastic Agents/pharmacology , Cell Proliferation , Lung Neoplasms/metabolismABSTRACT
Gamma-aminobutyric acid (GABA) is a principal inhibitory neurotransmitter in the central nervous system and is produced by irreversible decarboxylation of glutamate. It possesses several physiological functions such as neurotransmission, diuretic, and tranquilizer effects and also regulates cardiovascular functions such as blood pressure and heart rate in addition to playing a role in the reduction of pain and anxiety. The objective of this study was to evaluate the GABA producing ability and probiotic capability of certain lactic acid bacteria strains isolated from dairy products. Around sixty-four bacterial isolates were collected and screened for their ability to produce GABA from monosodium glutamate, among which nine isolates were able to produce GABA. The most efficient GABA producer was Enterococcus faecium BS5. Further, assessment of several important and desirable probiotic properties showed that Ent. faecium BS5 was resistant to acid stress, bile salt, and antibiotics. Ent. faecium BS5 may potentially be used for large-scale industrial production of GABA and also for functional fermented product development.
