Tetrahydrobiopterin from cyanide‐degrading bacterium Bacillus pumilus strain SVD06 induces apoptosis in human lung adenocarcinoma cell (A549)

Author:

Mahendran Ramasamy12ORCID,Selvaraj Sanjay Prasad34,Dhanapal Anand Raj5,sarasa Sabna Bhaskaran1,Mathias Beutline Malgija6,Thankappan Bency1,Femil Selta Daniel Raja7,Naveen Palanivel8,Poorani Rhenghachar9,Sundhar Navaneethan10,Pillai Mamatha M.11,Selvakumar Rajendran11,Huang Chih‐Yang212131415ORCID,Eswaran Raju16,Angayarkanni Jayaraman1ORCID

Affiliation:

1. Cancer Therapeutics Laboratory, Department of Microbial Biotechnology Bharathiar University Coimbatore Tamil Nadu India

2. Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan

3. Molecular and Biological Agricultural Science Program, Taiwan International Graduate Program Academia Sinica Taipei Taiwan

4. Graduate Institute of Biotechnology National Chung Hsing University Taichung Taiwan

5. Institute of Forest Genetics and Tree Breeding (IFGTB) Forest Campus Coimbatore Tamil Nadu India

6. Computational Science Laboratory, MCC‐MRF Innovation Park Madras Christian College Chennai Tamil Nadu India

7. Department of Biochemistry and Cancer Research Center FASCM, Karpagam Academy of Higher Education Coimbatore Tamil Nadu India

8. Department of Chemistry Sona College of Arts and Science Salem Tamil Nadu India

9. Gayatri Vidya parishad Institute of Health Care and Medical Technology Visakhapatnam India

10. Graduate Institute of Biomedical Sciences, School of Medicine China Medical University Taichung Taiwan

11. Tissue Engineering Laboratory PSG Institute of Advanced Studies Coimbatore Tamil Nadu India

12. Department of Biological Science and Technology, College of Life Sciences China Medical University Taichung Taiwan

13. PhD Program for Biotechnology Industry China Medical University Taichung Taiwan

14. Department of Medical Research, China Medical University Hospital China Medical University Taichung Taiwan

15. Department of Biotechnology Asia University Taichung Taiwan

16. Department of Zoology The Madura College Madurai Tamil Nadu India

Abstract

AbstractTetrahydrobiopterin (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.

Publisher

Wiley

Subject

Process Chemistry and Technology,Drug Discovery,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,General Medicine,Bioengineering,Biotechnology

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