Comparison of the Metabolite Profiles of HT-29 Colorectal Cancer Cells Treated with Curcumin, Cisplatin, 5-Fluorouracil and Doxorubicin in a Metabolomic Approach

 Chemotherapy for colorectal cancer often leads to significant adverse effects on patients, underscoring the need for alternative treatments. Herbal medicines like curcumin are considered a valuable complementary therapy due to their low toxicity profile and potential to mitigate the side effects of chemotherapy. Curcumin's mechanism of action targets multiple pathways, with untargeted metabolomic analysis helping to understand its exact mechanisms and subsequent treatment response. The aim of this study was to compare HT-29 cancer cell metabolites after curcumin and chemotherapy drug interventions to identify metabolites that can predict similar mechanisms of action between these treatments. Principal Component Analysis (PCA) of Fourier transform infrared spectroscopy (FTIR) absorption spectrum showed similar metabolite profiles in HT-29 cell culture media treated with curcumin and the chemotherapeutic cisplatin. Five cell metabolomes emerged after additional gas chromatography mass spectrometry/mass spectrometry (GC-MS/MS) and MS-DIAL data annotation: 1-bromo-2-chloroethane, 2-cyanoacetamide, dimethylamine (DMA), 2-nitrobenzo acid, and butane. The confusion matrix of these five annotated metabolites could be distinguished in HT-29 cell cultures treated with curcumin, but not in control cell cultures or those treated with the drugs cisplatin, doxorubicin, or 5-fluorouracil (5-FU). 2-cyanoacetamide in particular can be used as a marker of HT-29 cells' response to treatment with curcumin based on a p-value of < 0.05. According to these findings, no metabolite can predict the resemblance of curcumin's mechanism of action to chemotherapeutic medicines. Further study should therefore focus on in vivo experimental validation and upgrading metabolomic analysis technologies to further establish the similarities in the metabolite profiles of curcumin and cisplatin treatments.    Keywords: Curcumin, Colorectal Cancer,