Inhibitor of the transcription factor NF-κB, DHMEQ, enhances the effect of paclitaxel on cells of anaplastic thyroid carcinoma in vitro and in vivo

• Main Authors: V. V. Pushkarev, D. V. Starenki, V. M. Pushkarev, O. I. Kovzun, M. D. Tronko
• Format: Article
• Language: English
• Published: National Academy of Sciences of Ukraine and Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine. 2015-06-01
• Series: Ukrainian Biochemical Journal
• Subjects: anaplastic cancer; apoptosis; NF-κВ; paclitaxel; thyroid
• Online Access: http://ukrbiochemjournal.org/wp-content/uploads/2015/07/Pushkarev_3_15.pdf

Anticancer drug paclitaxel (Ptx) effect on biochemical mechanisms, regulating apoptosis in anaplastic thyroid carcinoma cells, was studied. It was shown that in addition to apoptotic cell death, Ptx induces signa­ling cascades that ensure cell survival. Paclitaxel-induced activation of nuclear factor kappa B (NF‑κВ) leads to an increase of some antiapoptotic proteins expression such as survivin, cIAP, XIAP. A novel NF‑κВ inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), was found to enhance cytotoxic effect of Ptx in anaplastic thyroid carcinoma cells. An enhancement of caspase-3 and -9 activation and PARP cleavage as well as the decreased levels of proteins-inhibitors of apoptosis were observed when cells were treated with a combination of both drugs. Mitochondria transmembrane potential (ΔΨm) loss was observed at higher concentrations of Ptx and DHMEQ. NF-κВ inhibition also potentiates paclitaxel effect at tumors formed by xenotransplantation of FRO cells into mice. Tumor mass reduction, significantly different from the effects of each of the compounds alone, was observed in animals, treated with paclitaxel and NF-κВ inhibitor. Thus, the combined use of paclitaxel and NF-κВ inhibitor inhibits biochemical processes that contribute to the resistance of anaplastic thyroid carcinoma cells to paclitaxel action.