Pharmacogenomic Characterization and Isobologram Analysis of the Combination of Ascorbic Acid and Curcumin—Two Main Metabolites of Curcuma longa—in Cancer Cells

<i>Curcuma longa</i> has long been used in China and India as anti-inflammatory agent to treat a wide variety of conditions and also as a spice for varied curry preparations. The chemoprofile of the <i>Curcuma</i> species exhibits the presence of varied phytochemicals with curcumin being present in all three species but AA only being shown in <i>C. longa</i>. This study explored the effect of a curcumin/AA combination on human cancer cell lines. The curcumin/AA combination was assessed by isobologram analysis using the Loewe additivity drug interaction model. The drug combination showed additive cytotoxicity toward CCRF-CEM and CEM/ADR5000 leukemia cell lines and HCT116p53^+/+ and HCT116p53^-/- colon cancer cell line, while the glioblastoma cell lines U87MG and U87MG.ΔEGFR showed additive to supra-additive cytotoxicity. Gene expression profiles predicting sensitivity and resistance of tumor cells to induction by curcumin and AA were determined by microarray-based mRNA expressions, COMPARE, and hierarchical cluster analyses. Numerous genes involved in transcription (<i>TFAM, TCERG1, RGS13, C11orf31</i>), apoptosis-regulation (<i>CRADD, CDK7, CDK19, CD81, TOM1</i>) signal transduction (<i>NR1D2, HMGN1, ABCA1, DE4ND4B, TRIM27</i>) DNA repair (<i>TOPBP1, RPA2</i>), mRNA metabolism (<i>RBBP4, HNRNPR, SRSF4, NR2F2, PDK1, TGM2</i>), and transporter genes (<i>ABCA1</i>) correlated with cellular responsiveness to curcumin and ascorbic acid. In conclusion, this study shows the effect of the curcumin/AA combination and identifies several candidate genes that may regulate the response of varied cancer cells to curcumin and AA.