Gercumin synergizes the action of 5-fluorouracil and oxaliplatin against chemoresistant human cancer colon cells.
Advanced colon cancer is extremely difficult to cure, underscoring the need to develop novel therapeutic agents. Prenylated curcumins that are semisynthetic curcumin derivatives with significant anti-cancer potential have been studied herein to assess their therapeutic potential for colon cancer and tested to this aim in vitro for their growth inhibitory properties against 5-fluorouracil + oxaliplatin resistant human colon cancer CR-HT29 and HCT-116 cells. The resulting most active product, gercumin (mono-O-geranylcurcumin), has been further tested for its synergistic effects with FOLFOX (a combination of 5-fluorouracil and oxaliplatin) on the same cell lines. Activity of this combination on colonosphere formation was also investigated. Gercumin was able to suppress the growth of cancer cells with a potency similar to that of curcumin. A synergistic effect of this compound and FOLFOX was also observed. doses tested for synergy in the colonosphere assays did not show greater suppression of colonosphere formation than independent treatment with either reagent alone. Only one of the combinations was shown to be more effective at suppressing colonosphere formation [gercumin 5  μM + FOLFOX (2x)]. Thus, the growth inhibitory effects of curcumin against human cancer cells can be modulated and enhanced by the introduction of hydrophobic chains, normally found in several natural compounds, like the geranyl one. Such compounds are also able to synergize with known chemotherapeutics.
['Genovese|Salvatore|S|', 'Epifano|Francesco|F|', 'Preziuso|Francesca|F|', 'Slater|Jill|J|', 'Nangia-Makker|Pratima|P|', 'Majumdar|Adhip P N|APN|', 'Fiorito|Serena|S|']
D000970:Antineoplastic Agents D000971:Antineoplastic Combined Chemotherapy Protocols D017209:Apoptosis D045744:Cell Line, Tumor D049109:Cell Proliferation D003110:Colonic Neoplasms D003474:Curcumin D019008:Drug Resistance, Neoplasm D004354:Drug Screening Assays, Antitumor D004357:Drug Synergism D005472:Fluorouracil D045325:HCT116 Cells D019073:HT29 Cells D006801:Humans D009944:Organoplatinum Compounds D000077150:Oxaliplatin
Gercumin Colon cancer Curcumin Geranylation Cancer chemotherapy