Hypoxic conditions by Raman microspectroscopy – Reprogramming of fatty acids and glucose metabolism during colon cancer progression

Cellular respiration is the primary metabolic process for producing the energy (ATP) needed for survival. Disruptions in this process can lead to various diseases, including colon cancer. This paper reviews the current understanding of how excess fatty acids (FAs) and glucose (Glc) alter metabolic pathways. We focused on the impact of unsaturated fatty acids (UFAs) (eicosapentaenoic acid (EPA), linoleic acid (LA)), saturated fatty acid (SFA) (palmitic acid (PA)), and glucose on healthy human colon cells (CCD-18 Co) and cancerous colon cells (Caco-2) using Raman microspectroscopy. Our study examined the metabolic abnormalities in mitochondria and lipid droplets caused by the external intake of FAs and glucose. The results indicate that the peaks at 750 cm⁻¹, 1004 cm⁻¹, 1256 cm⁻¹, 1444 cm⁻¹, and 1656 cm⁻¹ can serve as Raman biomarkers for monitoring metabolic pathways in colon cancer. We proved that oxidative metabolism towards glycolysis allows maintaining redox homeostasis and enables the survival and proliferation of cancer cells in hypoxic conditions. Our findings show that comparing control cells with cells supplemented with UFAs, SFA, and glucose can help detect metabolic abnormalities. Specifically, supplementation with UFAs reduces the intensity of the bands at 750 cm⁻¹ and 1004 cm⁻¹, while SFA and glucose increase their intensity. For the bands at 1256 cm⁻¹, 1444 cm⁻¹, and 1656 cm⁻¹, palmitic acid and glucose decrease the intensity, whereas linoleic acid increases it. This paper introduces new experimental techniques, such as Raman microspectroscopy and imaging, to track and understand the metabolic changes in colon cells caused by FAs and glucose under hypoxic conditions.