Introduction.

CIGB-300 is an antitumor peptide that inhibits the CK2-mediated phosphorylation by direct targeting of substrates. This paper aims to describe breakthroughs about the CIGB-300 antineoplastic mechanism related to the inhibition of CK2-mediated phosphorylation and the synergism with anticancer drugs.

Methods.

CK2 phosphorylation assays were performed with catalytic CK2α subunit or the CK2 holoenzyme in presence or not of CIGB-300. CIGB-300/CK2 interaction was verified by pull-down experiments, in situ colocalization and phosphoproteomic analysis of CIGB-300-treated lung cancer cells were also performed. Synergism of the peptide with anticancer drugs was evaluated in vitro and for Cisplatin; it was also tested in vivo. Besides, comparative proteomics of CIGB-300 combined with Cisplatin was conducted.

Results.

CIGB-300 targeted the CK2α subunit and inhibited the enzymatic activity of the holoenzyme in different experimental settings. Likewise, phosphoproteomic and Western Blot analysis allowed for knowing the early CK2 inhibition profile elicited by CIGB-300 at 10 and 30 minutes of treatment. Moreover, CIGB-300 did synergize with chemotherapeutics and EGFR inhibitors, and molecular events that reportedly support such synergistic interactions were also known. Conclusions. CIGB-300 inhibits the CK2-mediated phosphorylation by using an alternative mechanism of direct interaction with the enzyme itself. Besides, CIGB-300 synergizes with chemotherapeutics and EGFR inhibitors by modulating different proteins related to drug resistance.

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