Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Aug 12;151(8):229.
doi: 10.1007/s00432-025-06282-y.

Role of paraoxonase 2 (PON2) as a potential biomarker and therapeutic target in cancer treatment

Vinayak Agarwal  1 , Matthew Cheesman  1 , Alison Haywood  1   2 , Sohil Khan  1 , Shailendra Anoopkumar Dukie  3
Affiliations
Review

Role of paraoxonase 2 (PON2) as a potential biomarker and therapeutic target in cancer treatment

Vinayak Agarwal et al. J Cancer Res Clin Oncol. .

Abstract

Purpose: Paraoxonase 2 (PON2), a mitochondrial antioxidant enzyme, is widely expressed across body tissues and plays vital roles in cellular defence. Growing evidence links its dysregulation to oxidative stress and cancer progression. This narrative review aims to elucidate PON2's enzymatic characteristics and explore its potential modulation as an innovative therapeutic avenue for combating cancer.

Methods: This narrative review provides a comprehensive evaluation of the roles of paraoxonase 2 in cancer, with a focus on its regulatory mechanisms and potential utility as a biomarker for targeted therapeutic interventions. A comprehensive analysis of the scientific literature from 1924 to 2024 was carried out, with studies retrieved from PubMed, Web of Science, and Scopus. Following a comprehensive screening process, 27 studies were included in the review.

Results: The outcomes underscore PON2's complex involvement in cancer biology, spanning tumour initiation, progression, and therapeutic resistance. The antioxidant attributes of PON2 play a critical role in helping cancer cells combat chemotherapy by allowing them to sustain oxidative stress. PON2 regulates essential features of the cancer cell lifecycle, such as invasion, migration, and proliferation. Its impact on apoptosis makes it promising as a biomarker for prognosis and diagnostics as well as a therapeutic target, especially for patients with drug-resistant cancers.

Conclusion: This review highlights PON2's involvement in carcinogenesis in detail. Future research should focus on elucidating the molecular mechanisms regulating PON2 and exploring its potential as a target for the development of effective cancer therapies.

Keywords: Cancer biomarker; Chemotherapy resistance; Oxidative stress; Paraoxonase 2 (PON2); Prognostic marker; Therapeutic target.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Competing interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PON2 as a key regulator of oxidative stress and apoptosis in cancer progression. Abbreviation: PON2: paraoxonase 2; Cyt C: cytochrome c; ROS: reactive oxygen species; CHOP: C/EBP homologous protein; ER: endoplasmic reticulum; INK: INK4 family of cyclin-dependent kinase inhibitors; IRE1: Inositol-Requiring Enzyme 1; TRAF2: TNF Receptor–Associated Factor 2; ASK1: Apoptosis Signal-Regulating Kinase 1
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Altenhöfer S, Witte I, Teiber JF et al (2010) One enzyme, two functions: PON2 prevents mitochondrial superoxide formation and apoptosis independent from its lactonase activity. J Biol Chem 285:24398–24403. 10.1074/jbc.M110.118604 - PMC - PubMed
    1. Ayan D, Gül MA, Karabay U, Bulut SM (2024) Bioinformatic investigation of genetic changes in paraoxonase genes in breast cancer and breast cancer subtypes. Eur J Breast Health 20:178. 10.4274/EJBH.GALENOS.2024.2024-3-7 - PMC - PubMed
    1. Bacchetti T, Sartini D, Pozzi V et al (2017) Exploring the role of paraoxonase-2 in bladder cancer: analyses performed on tissue samples, urines and cell cultures. Oncotarget 8:28785–28795. 10.18632/ONCOTARGET.15674 - PMC - PubMed
    1. Bacchetti T, Salvolini E, Pompei V et al (2021) Paraoxonase-2: a potential biomarker for skin cancer aggressiveness. Eur J Clin Invest 51:e13452. 10.1111/eci.13452 - PubMed
    1. Bacchetti T, Campagna R, Sartini D et al (2022) C. spinosa L. subsp. rupestris phytochemical profile and effect on oxidative stress in normal and cancer cells. Molecules. 10.3390/molecules27196488 - PMC - PubMed

LinkOut - more resources