Microtubules are polymers of microtubule proteins that form part of the cytoskeleton and provide structure and shape for eukaryotic cells. Specifically, Microtubules play an important role in many cellular processes. They participate in maintaining cellular structure and form the cytoskeleton together with microfilaments and intermediate filaments. Besides, Microtubes are highly dynamic structures composed of α- And β- Tubulin heterodimer composition. In the context of cancer, the tubulin family is a target for tubulin-binding chemotherapy drugs. Moreover, it inhibits the dynamics of the mitotic spindle, leading to mitotic arrest and cell death.
Furthermore, Microtubules are the driving force for the extension of neural processes. Like actin, many signal pathways involved in neuronal polarization affect proteins that regulate microtubule stability and dynamics. During the polymerization process, α/β- Microtubulin heterodimers are into linear filaments, which combine laterally to form hollow microtubule cylinders. Compounds targeting microtubules have potential clinical utility and are generally classified into two broad categories. In addition, one group includes promoting microtubule polymerization, while the other group inhibits microtubule polymerization. These microtubule targeting agents mainly alter the normal dynamic balance. Meanwhile, this can lead to microtubule stability or instability, leading to mitosis slowing or blocking the mid/late transition and subsequent triggering of apoptosis. Now, we will introduce a tubulin polymerization inhibitor, MPT0B014.
MPT0B014, a Tubulin Polymerization Inhibitor Induces Cancer Cell Apoptosis.
Next in importance, MPT0B014 with 0-1 μM for 48 h inhibits A549, H1299, and H226 cell growth in a dose-dependent manner. Nonetheless, MPT0B014 arrests the cell cycle at G2/M and sub-G1 phases and induces apoptosis in A549 cells.
Once again, the combination of MPT0B014 and Erlotinib significantly improves A549 tumor inhibition in mice. The combination produced significantly higher anti-tumor activity. Importantly, the growth of A549 cancer cell xenografts was suppressed by 11, 21, and 49% after treatment with MPT0B014, Erlotinib, and MPT0B014 plus Erlotinib, respectively.
All in all, MPT0B014 is a tubulin polymerization inhibitor and induces cancer cell apoptosis.