Lee, Seung Ho Son, Seung Mo Son, Dong Ju Kim, Sun Mi Kim, Tack Joong Song, Sukgil Moon, Dong Cheul Lee, Hyo Won Ryu, Jae Chun Yoon, Do-Young Hong, Jin Tae 2024-01-21T00:31:18Z 2024-01-21T00:31:18Z 2021-09-02 2007-10 1535-7163 https://pubs.kist.re.kr/handle/201004/134070 Molecular mechanisms underlying epothilone-induced apoptotic cell death were investigated in SW620 human colon cancer cells. Treatment with epothilone B and D at different concentrations (1 - 100 nmol/L) dose-dependently inhibited cell growth and caused cell cycle arrest at G2-M, which was followed by apoptosis. Consistent with this induction of apoptotic cell death, epothilone B and D enhanced the constitutional activation of nuclear factor-kappa B (NF-kappa B) via I kappa B degradation through I kappa B kinase (IKK alpha and IKK beta) activation, and this resulted in p50 and p65 translocation to the nucleus. Moreover, cells treated with sodium salicylic acid, an IKK inhibitor, or transiently transfected with mutant IKK alpha and beta did not show epothilone-induced cell growth inhibition or p50 translocation, although p65 was still translocated to the nucleus. Treatment with epothilone B and D also enhanced beta-tubulin polymerization and the formation of p50/beta-tubulin complex. However, beta-tubulin polymerization was not inhibited in the cells treated by sodium salicylic acid or transiently transfected with mutant IKK alpha and beta. Moreover, epothilone B and D increased the expressions of NF-kappa B-dependent apoptotic cell death regulatory genes, i.e., Bax, p53, and the active form of caspase-3, but reduced Bcl-2 expression, and these actions were partially reversed by salicylic acid. In addition, caspase-3 inhibitor reduced epothilone B-induced cell death and NF-kappa B activation. These findings suggest that the activation of NF-kappa B/IKK signals plays an important role in the epothilone-induced apoptotic cell death of SW620 colon cancer cells in a tubulin polymerization - independent manner. English AMER ASSOC CANCER RESEARCH PACLITAXEL-INDUCED APOPTOSIS MITOTIC ARREST TUMOR-CELLS DNA-BINDING IKK-BETA INHIBITION PHOSPHORYLATION TRANSCRIPTION EXPRESSION PROTEINS Epothilones induce human colon cancer SW620 cell apoptosis via the tubulin polymerization-independent activation of the nuclear factor-kappa B/i kappa B kinase signal pathway Article 10.1158/1535-7163.MCT-07-0002 1 MOLECULAR CANCER THERAPEUTICS, v.6, no.10, pp.2786 - 2797 MOLECULAR CANCER THERAPEUTICS 6 10 2786 2797 scie scopus 000250252100019 2-s2.0-35848969354 Oncology Oncology Article PACLITAXEL-INDUCED APOPTOSIS MITOTIC ARREST TUMOR-CELLS DNA-BINDING IKK-BETA INHIBITION PHOSPHORYLATION TRANSCRIPTION EXPRESSION PROTEINS nuclear factor-kB/IkB kinase Human colon cancer cell epothiolone apoptosis tubulin polymerization-independent activation