Inhibition of non-small cell lung cancer (NSCLC) proliferation through targeting G6PD

Makamas Chanda; Pornchai Anuntasomboon; Komkrit Ruangritchankul; Poonlarp Cheepsunthorn; Chalisa L Cheepsunthorn

doi:10.7717/peerj.16503

Inhibition of non-small cell lung cancer (NSCLC) proliferation through targeting G6PD

PeerJ. 2023 Dec 5:11:e16503. doi: 10.7717/peerj.16503. eCollection 2023.

Authors

Makamas Chanda^#¹, Pornchai Anuntasomboon^#², Komkrit Ruangritchankul³, Poonlarp Cheepsunthorn⁴, Chalisa L Cheepsunthorn⁵

Affiliations

¹ Interdisciplinary Program of Biomedical Sciences, Graduate School, Chulalongkorn University, Bangkok, Thailand.
² Medical Sciences Program, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
³ Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁴ Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁵ Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

^# Contributed equally.

Abstract

Background: Mounting evidence has linked cancer metabolic reprogramming with altered redox homeostasis. The pentose phosphate pathway (PPP) is one of the key metabolism-related pathways that has been enhanced to promote cancer growth. The glucose 6-phosphate dehydrogenase (G6PD) of this pathway generates reduced nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for controlling cellular redox homeostasis.

Objective: This research aimed to investigate the growth-promoting effects of G6PD in non-small cell lung cancer (NSCLC).

Methods: Clinical characteristics and G6PD expression levels in lung tissues of 64 patients diagnosed with lung cancer at the King Chulalongkorn Memorial Hospital (Bangkok, Thailand) during 2009-2014 were analyzed. G6PD activity in NSCLC cell lines, including NCI-H1975 and NCI-H292, was experimentally inhibited using DHEA and siG6PD to study cancer cell proliferation and migration.

Results: The positive expression of G6PD in NSCLC tissues was detected by immunohistochemical staining and was found to be associated with squamous cells. G6PD expression levels and activity also coincided with the proliferation rate of NSCLC cell lines. Suppression of G6PD-induced apoptosis in NSCLC cell lines by increasing Bax/Bcl-2 ratio expression. The addition of D-(-)-ribose, which is an end-product of the PPP, increased the survival of G6PD-deficient NSCLC cell lines.

Conclusion: Collectively, these findings demonstrated that G6PD might play an important role in the carcinogenesis of NSCLC. Inhibition of G6PD might provide a therapeutic strategy for the treatment of NSCLC.

Keywords: DHEA; Glucose 6-phosphate dehydrogenase; Lung cancer; Metabolic reprogramming; NSCLC; Non-small cell lung cancer; PPP; Pentose phosphate pathway; Squamous cells; siG6PD.

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Cell Proliferation
Homeostasis
Humans
Lung Neoplasms* / drug therapy
Thailand

Grants and funding

This study was supported by the 100th Anniversary Chulalongkorn University Fund for Doctoral Scholarship, the 90th Anniversary of Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund), Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University (Grant No. 065/24) (Grant No. RA61/039) and the Thailand Government Budget Fund 2018 (Ratchadaphiseksomphot Endowment Fund) (Grant No. 1GB_CU_61_22_30_12). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.