Raman spectroscopy reveals oxidative stress-induced metabolic vulnerabilities in early-stage AR-negative prostate-cancer versus normal-prostate cell lines

Sep 21, 2026

Uploaded by Skyler

Quantitative Raman spectroscopy is used to molecularly compare a low-grade, Gleason-3, AR-negative prostate-cancer cell line (P4E6) with a normal prostate cell-line equivalent (PNT2-C2), leveraging live-state measurements to capture molecular heterogeneity. Spectral population sampling identifies reduced DNA/RNA signatures, increased protein synthesis signatures, decreased saturated and unsaturated fatty acids, and elevated cholesterol and cholesterol esters. The live-cell disease state indicates Warburg-effect aerobic glycolysis, while an air-drying desiccation model reveals survival mechanisms linked to DNA/RNA structural robustness, metabolic rerouting, and reduced protein synthesis, limiting oxidative-damage resistance.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Prostate cancer complexity and molecular heterogeneity

Raman spectroscopy as a complementary approach

Methods and Study Design

Cell-line models: P4E6 vs PNT2-C2

Live-state and desiccation (air-drying) comparison

Results Focus

Live-state biomarker identification

Mechanistic strengths and weaknesses after catastrophic desiccation

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Raman spectroscopy reveals oxidative stress‑induced metabolic vulnerabilities in early‑stage AR‑negative prostate‑cancer versus normal‑prostate cell lines M. Cameron1, F. Frame2,3, N. J. Maitland2,3 & Y. Hancock1,3* Quantitative Raman spectroscopy provides information‑rich imaging of complex tissues. To illustrate its ability to characterise early‑stage disease, we compared live P4E6, a low‑grade Gleason‑3 prostate‑cancer cell line, to PNT2‑C2, a normal prostate cell‑line equivalent, thereby elucidating key molecular and mechanistic differences. Spectral changes from statistically relevant population sampling show P4E6 is defined by reduced DNA/RNA signatures (primarily base‑pair modifications), increased protein‑related signatures (synthesis), decreased whole‑cell measured saturated and unsaturated fatty acids, and increased cholesterol and cholesterol ester (lipid storage) . Signatures in the live‑cell disease state point to the Warburg effect for aerobic glycolysis as the mechanism for cellular energy generation. A follow‑on study involving catastrophic desiccation showed a key survival pathway in the cancer state in the structural robustness of DNA/RNA. Metabolic changes, namely in Warburg‑to‑oxidative‑phosphorylation rerouting and reduced protein synthesis, were also shown. Such modifications limit cancer’s resistance to oxidative damage, and thus its ability to utilise a higher redox homeostasis for metabolic advantage. The results demonstrate the ability of quantitative Raman spectroscopy to uncover, with full molecular‑heterogeneity capture, mechanistic vulnerabilities in lowest‑grade tumorigenic prostate cancer, thereby revealing underlying targets for disease disruption at early stage. Prostate cancer is the fourth most commonly diagnosed cancer across all genders and second most common cancer in males, with 1.4M new cases in 2020 worldwide1. Molecular characterisation of the disease, and determining the underpinning molecular-level mechanisms for its initiation and progression, are challenging due to its complexity and heterogeneity both within and between patients, at the single-cell, and inter-and intratumoral levels, and in the metastatic state. Genomic studies of prostate cancer show stratification to subtypes well beyond clinical measures of Gleason score, lymph-node invasion, and tumour grade2. In transcriptomic studies, the disease state exhibits complex mechanistic pathways and spatial heterogeneity in its classification and progression3. Length-scale complexities are also apparent, whereby genomic and transcriptomic aberrations do not to correlate to disease-related changes at other molecular length scales, such as in proteins and lipids4,5. As such, there are unresolved issues in combining across separate genomic, lipidomic and proteomic studies that involve destructive testing, as well as testing under different environmental conditions. To assist with these limitations and challenges, Raman spectroscopy is proposed as a complementary approach for label-free, molecular-scale characterisation of intact specimens. Raman spectroscopy molecularly fingerprints samples via non-destructive, laser light (photon-molecule-scattering) interaction—the so-called Raman effect6. Raman spectroscopy has potential for biomedical applications in diagnostics and in treatment studies across a broad range of diseases and system types7. Specific to prostate cancer is its use to characterise the disease state of cellular components (e.g., exosomes)8, single cells9, and tissue samples10, 11. Raman spectroscopy has also been used to elucidate mechanisms for treatment action12, as well as to monitor treatment response, such as in lipid droplets in prostate-cancer cells13, 14. Pertinent to the study of molecular heterogeneity, which 1School of Physics, Engineering and Technology, University of York, Heslington, York YO10 5DD, UK. 2Department of

FAQs

How does the study use quantitative Raman spectroscopy to compare disease states?

It performs Raman spectroscopy on live P4E6 and live PNT2-C2 cells to derive statistically supported spectral differences, then uses Raman biomarkers to characterize additional changes after catastrophic desiccation (air-drying).

What metabolic and molecular signatures distinguish P4E6 from PNT2-C2 in the live state?

P4E6 shows reduced DNA/RNA signatures, increased protein-related synthesis signatures, decreased measured saturated and unsaturated fatty acids, and increased cholesterol and cholesterol esters, pointing to Warburg-like aerobic glycolysis.

What does the desiccation follow-on study reveal about cancer vulnerabilities?

Air-drying drives key biomarker shifts in the cancer state relative to normal dried results, highlighting survival reliance on DNA/RNA structural robustness and metabolic rerouting from Warburg to oxidative phosphorylation, alongside reduced protein synthesis.

Sep 21, 2026

Uploaded by Skyler