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Purpose: The azide methyl anthraquinone derivative 6-azidomethyl -1-hydroxyl-3,8-dimethoxy-9,10-anthraquinone (AHDA) is a novel emodin derivate. The study was designed to investigate the effect of AHDA on cytotoxicity and its synergy effect with conventional chemotherapeutical agents. Methods: Cytotoxicity was measured by MTT assay. The cell cycle arrest effect was assessed by flow cytometry. The drug combination index (CI50) on 50% level of cytotoxicity was calculated. A CI50 less than 1 indicated synergy effect, a CI50 equal to 1 indicated additivity effect, and a CI50 greater than 1 indicated antagonism effect. Results: Of 30 human cancer cell lines, AHDA exhibited potent cytotoxicity in epidermoid carcinoma KB cells, leukemia HL-60 cells, tongue cancerTca-8113 cells and esophageal cancer Eca-109 cells. The IC50s of AHDA in KB cells, HL-60 cells, Tca-8113 cells and ECA-109 cells were 0.0129±0.0069 μM, 0.0183±0.0099 μM, 0.27740±1939 μM and 0.2895±0.0181 μM, respectively. But colorectal cancerLoVo cells and osteosarcoma MG-63 cells were less sensitive to AHDA and IC50s were all more than 50 μM. Interestingly, AHDA exhibited more potent cytotoxicity to multidrug resistant (MDR) breast cancer MCF-7/Adr cells than drug-sensitive parental MCF-7 cells, and the IC50s were 0.6860±0.1446 μM and 1.8753±0.3950 μM, respectively. KB cells treated with 0.02 μM AHDA for 24 hr results in cell cycle S phase arrest. AHDA combination with topotecan, mitomycin, gemcitabine or bleomycin appeared significant synergic effect in KB cells and the combination indexes (CI50) were 0.601, 0.647, 0.782 and 0.921, respectively. However, an antagonism effect was exhibited when KB cells were treated with AHDA combination with arabinoside, epirubicin, cisplatin, etoposide, 5-fluorouracil, or vincristine and CI50 were 1.120, 1.123, 1.770, 2.000, 2.263 and 2.319, respectively. Conclusion: AHDA appeared potent cytotoxicity in KB cells, HL-60 cells, Tc-8113 cells and ECA-109 cells and resulted in cell cycle S phase arrest. A synergic effect was exhibited when AHDA combined with topotecan, mitomycin, gemcitabine or bleomycin, respectively.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA