NF-kappaB pathway has been proven to be critical to survival of lung cancer cells, and many natural products from plants were shown to inhibit the activation of this pathway. In this study, we investigated the effects of two cardamonin analogs, 4,4"-dihydroxylchalcone (DHC) and 4,4"-dihydroxy-2"-methoxychalcone (DHMC), on survival of lung cancer cells and the involved mechanisms. MTT assay revealed that the two compounds potently decreased the survival of immortalized and primary lung cancer cells. DHC and DHMC were able to induce apoptosis in A549 and NCI-H460 cells. Immunoblotting, immunofluorescent staining, and luciferase reporter further demonstrated that the two compounds suppressed the activation of NF-kappaB pathway in lung cancer cells. PMA-mediated NF-kappaB reactivation abrogated the effect of DHC and DHMC on lung cancer cells. DHC and DHMC were also shown to suppress the growth of A549 xenograft in mice. Collectively, we verified two cardamonin analogs as novel compounds suppressing NF-kappaB signaling for lung cancer therapy.
[1]Changchun Univ Chinese Med, Affiliated Hosp, Emergency Dept, Changchun 130103, Peoples R China.
[2]Changchun Univ Chinese Med, Affiliated Hosp, Dept Radiol, Changchun 130103, Peoples R China.
[3]Changchun Univ Chinese Med, Affiliated Hosp, Dept Pharm, Changchun 130103, Peoples R China.
[4]Jilin Univ, Hosp 1, Cardiovasc Dept, Changchun 130033, Peoples R China.
[5]Jilin Univ, Hosp 1, Emergency Dept, Changchun 130033, Peoples R China.
(8.0+极速模式)