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ID: 93: STRUCTURE-ACTIVITY RELATIONSHIPS OF SYNTHESIZED QUERCETIN DERIVATIVES ON ANTI-PROLIFERATION AND ANTI-MIGRATION ACTIVITY IN B16 MELANOMA CELLS
  1. K Yamauchi1,2,
  2. SH Afroze1,
  3. T Mitsunaga2,
  4. MN Uddin3,4
  1. 1Medical Physiology, Texas A&M Health Science Center College of Medicine, Temple, Texas, United States
  2. 2United Graduate School of Agricultural Science, Gifu University, Gifu, Gifu, Japan
  3. 3Obstetrics and Gynecology, Baylor Scott & White Health/Texas A&M Health Science Center College of Medicine, Temple, Texas, United States
  4. 4Pediatrics, Baylor Scott & White Health/Texas A&M Health Science Center College of Medicine, Temple, Texas, United States

Abstract

Objective Quercetin is a representative flavonoid that presents widely in variety of foods and medicinal plants. So far quercetin has been reported to inhibit migration and invasion of cancer via decreasing the matrix metalloproteinase (MMP)-2. A quercetin glycoside and 7 methylquercetins were synthesized from rutin as a starting material in order to evaluate the effect on anti-proliferation and anti-migration activity in B16 melanoma cells.

Study Design The migration assay was performed using 8 µm pore insert by a CytoSelect Assay (Cell Biolabs). Cell viability was measure using a CellTiter Assay (Promega). A 10% and 0.5% fetal bovine serum (FBS) including Dulbecco's modified Eagle medium (DMEM) were used respectively to investigate the proliferation and cytotoxicity of the quercetin derivatives.

Results 3-O-methylquercetin (3MMQ) exhibited 30, 38, 45% migration activity at 25, 12.5, 6.25 µM respectively that is more potent than that of quercetin. 3,7-O-dimethylquercetin (37DMQ) also inhibited migration to 44, 70, 99% at the same concentrations. Furthermore, 3,4′,7-O-trimethylquercetin (34'7TMQ) and 3,4′-O-dimethylquercetin (34'DMQ) potently inhibited migration to 22, 31, 35% and 28, 33, 59% respectively at the same concentrations. Quercetin glycoside,4′-O-β-D-glucopyranosyl-quercetin-3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyra-noside, and 7,4'-O-dimethyquercetin (74'DMQ) didn't inhibit migration, and 4′-O-methylquercetin (4'MMQ) and 7-O-methylquecetin (7MMQ) elicited modest inhibition with no statistical significance. 3MMQ, 4'MMQ, 7MMQ, 4'7DMQ, 34'7TMQ would elicit no effect on the cell proliferation, while 37DMQ and 34'DMQ decreased cell viability with about 50% at 12.5 µM using B16 melanoma cells when cultured with 10% FBS DMEM. In contrast 37DMQ and 34'DMQ exhibited no cytotoxicity in the cells when cultured with 0.5% FBS DMEM.

Conclusion These data indicate that the methoxyl group at C-3 position plays an important role to inhibit migration in B16 melanoma cells. Among the quercetin derivatives showing potent anti-migration activity, 34'7TMQ inhibited migration at most which suggests that the methoxyl groups at C-4' and 7 would accelerate the activity. The data on cell proliferation and cytotoxicity exhibit that 37DMQ and 34'DMQ inhibit proliferation of the cancer cells without cytotoxicity to the cells.

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