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Abstract 5819: Colossolactone-G enhances the anticancer properties of 5-fluorouracil and gemcitabine against colorectal cancer cells

The use of anti-cancer adjuvant therapy is rationalized by potentiating the efficacy, and/or protecting from major side effects of chemotherapeutics. Gemcitabine and 5-fluorouracil are important chemotherapeutic agents which are frequently used to treat cancers such as colorectal cancer. Colossolact...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.5819-5819
Main Authors: Aljohani, Rinad A., Hegazy, Gehan A., Alamoudi, Aliaa A., El-Halawany, Ali M., Eldine, Riham S., Agabnoor, Ghada, Al-Abd, Ahmed M.
Format: Article
Language:English
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Summary:The use of anti-cancer adjuvant therapy is rationalized by potentiating the efficacy, and/or protecting from major side effects of chemotherapeutics. Gemcitabine and 5-fluorouracil are important chemotherapeutic agents which are frequently used to treat cancers such as colorectal cancer. Colossolactone-G is a naturally occurring triterpenoid metabolite isolated from the fruiting body of Ganoderma colossum. Herein, we assessed the potential chemomodulatory effects of Colossolactone-G to 5-fluorouracil and gemcitabine against human colorectal cancer cells. After 72 h of exposure, colossolactone-G per se possesses cytotoxic effects against HCT116 and HT29 cells with IC50's of 15.9±3.6 µM and 90.5±1.7 µM, respectively. In addition, colossolactone-G improved the cytotoxic profile of gemcitabine against HCT116 cells reducing its IC50 from 0.28±0.1 µM to 19.41±3.1 nM with combination index indicative of synergism (CI-value = 0.154). Similarly, colossolactone-G enhanced the cytotoxicity of gemcitabine against HT29 cells reducing its IC50 from 6.2±1.1 µM to 0.6±0.3 µM with combination index indicative of synergism (CI-value = 0.219). Besides, colossolactone-G synergized the cytotoxic profile of 5-fluorouracil against HCT116 and HT29 cells decreasing its IC50's from 10.8±4.6 to 3.1±0.5 µM (CI-value = 0.302), and from 12.9±3.7 to 3.2±0.6 µM (CI-value = 0.426), respectively. By assessing cell cycle distribution after 24 h using DNA content flowcytometry, both gemcitabine and 5-fluorouracil induced moderate cell cycle arrest at S-phase which was increased by combination with colossolactone-G and was further extended to induce accumulation of cells at G0/G1-phase. Longer exposure (48 h) of cells to colossolactone-G alone induced antiproliferative effect and accumulation of cells at G0/G1-phase. Besides, the S-phase arrest induced by gemcitabine and 5-fluorouracil was further increased by combination with colossolactone-G for 48 h and was accompanied by reciprocal decrease in cells in G2/M-phase. Cell cycle arrest attributed to gemcitabine and 5-fluorouracil treatment resulted in increasing cells undergoing apoptosis as shown by annexin-V/FITC staining. Similarly, combination with colossolactone increased the percentage of cells undergoing apoptosis in both cell lines. In conclusion, colossolactone-G represents promising chemomodulatory compound of natural origin which improves the anti-colorectal cancer activity of gemcitabine and 5-fluorouracil in a cell cycle dependen
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2018-5819