title: Anticancer cardamonin analogs suppress the activation of NF-kappaB pathway in lung cancer cells.
abstract: 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.
authors.affiliation: Emergency Department of the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130103, China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: He
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xuebing
authors.initials: X
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Honglei
authors.initials: H
authors.lastname: Ji
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D016328:NF-kappa B; C436747:cardamonin