Disrupting CCT-β: β-tubulin selectively kills CCT-βoverexpressed cancer cells through MAPKs activation

Yan Jin Liu, Vathan Kumar, Yuan Feng Lin, Po Huang Liang

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


We have previously demonstrated the ability of I-Trp to disrupt the protein-protein interaction of β-tubulin with chaperonin-containing TCP-1β (CCT-β). This caused more severe apoptosis in multidrug-resistant MES-SA/Dx5, compared to MES-SA, due to its higher CCT-β overexpression. In this study, we screened a panel of cancer cell lines, finding CCT-β overexpression in the triple-negative breast cancer cell line MDA-MB-231, colorectal cancer cell lines Colo205 and HCT116, and a gastric cancer cell line MKN-45. Thus, I-Trp killed these cancers with sub-to low-μM EC"5"0, whereas it was non-toxic to MCF-10A. We then synthesized analogs of I-Trp and evaluated their cytotoxicity. Furthermore, apoptotic mechanism investigations revealed the activation of both protein ubiquitination/degradation and ER-associated protein degradation pathways. These pathways proceeded through activation of MAPKs at the onset of CCT-β: β-tubulin complex disruption. We thus establish an effective strategy to treat CCT-β overexpressed cancers by disrupting the CCT-β: β-tubulin complex.

Original languageEnglish
Article numbere3052
JournalCell Death and Disease
Issue number9
Publication statusPublished - Sep 14 2017
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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