Inhibition of Snail expression by an NF-κB inhibitor DHMEQ in non-small cell lung carcinoma cells Free

5356

[Introduction] We have designed and synthesized a novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ). DHMEQ inhibited the growth of prostate carcinoma, thyroid carcinoma, breast carcinoma, pancreatic carcinoma, multiple myeloma, and adult T-cell leukemia in nude or SCID mice. E-cadherin plays an essential role to form a tight cell-cell adhesion suppressing the dissociation of cells. Therefore, loss of E-cadherin in cancer cells may enhance metastasis. We previously reported that DHMEQ enhanced the expression of cadherin in non-small cell lung carcinoma cells. In the present research we studied the involvement of transcription factors in the mechanism of enhancement of E-cadherin expression. We also studied the molecular mechanism of NF-κB inhibition by DHMEQ. [Experimented procedures] We employed A549 non-small cell lung carcinoma cells. Nuclear translocation of NF-κB was examined by Western blotting after the fractionation. The NF-κB activity was measured by EMSA. Snail was detected by RT-PCR and Western blotting. [Summary] Addition of TNF-α reduced the expression of E-cadherin in A549 cells, and DHMEQ was shown to inhibit the decrease of E-cadherin by RT-PCR, Western blotting, and immunostaining analyses. As the mechanism of inhibition, it inhibited the TNF-α-induced E-Box promoter activation that regulates E-cadherin expression. DHMEQ also inhibited the expression of snail that can bind to E-Box. DHMEQ is known to inhibit nuclear translocation of NF-κB. Using A549 cells, we newly found that it also inhibited the binding of NF-κB in the nuclear fraction to κB DNA in vitro. [Conclusion] DHMEQ, an NF-κB inhibitor, inhibited the expression of snail that can suppress the E-cadherin expression in non-small cell lung carcinoma cells. These effects on E-cadherin expression may contribute to the antimetastatic and antitumor activities of DHMEQ in animals. DHMEQ is likely to inhibit both nuclear translocation and κB DNA binding of NF-κB in A549 cells.