Group Meeting

July 2011
Mariana Feij Fernandes

Cytotoxicity
Sulforaphane vs Oltipraz
MTT

SRB

Sulforaphane is a more cytotoxic compound with 10 IC50 30 M Sulforaphane was the chosen compound for combination in Synergy Assessment

Cytotoxicity
5-Fluorouracil vs Docetaxel
MTT

SRB

Docetaxel is a more cytotoxic compound with effective concentrations in the nM range Docetaxel was the chosen compound for combination in Synergy Assessment

Cytotoxicity
Docetaxel Concentrations
MTT

SRB

MTT assay shows big error Slight increase in cytotoxicity

Synergy???

NQO1 up-regulation
MCF7 cell line vs Hepa-1c7c cell line
MCF7

Sulforaphane alone

Docetaxel alone and in combination with Sulforaphane

Sulforaphane presents NQO1 up-regulation as it should The compound combination doesnt show NQO1 up-regulation in the concentrations tested

NQO1 up-regulation
MCF7 cell line vs Hepa-1c7c cell line
MCF7 Hepa-1c7c

Docetaxel doesnt induce NQO1 up-regulation Sulforaphane induces NQO1 up-regulation Hepa-1c7c cell line more inducible to NQO1 upregulation

Conclusions

SFN is a potent cytotoxic agent which interferes with the Keap1-Nrf2-ARE pathway, thus promoting the expression of NQO1 Phase II enzyme.

OLT doesnt reveal significant cytotoxic effect in concentrations of the M range.

SFN and 5-Fu combination doesnt reveal significant synergistic or additive effect in what concerns cytotoxicity. SFN and DOX combination doesnt reveal any synergistic or additive effect in what is related to the Keap1-Nrf2-ARE pathway, but there may be an increased cytotoxicity effect when the combination is used. MCF7 cell line is quite uninducible in what concerns NQO1 upregulation.