Components of antitumor extract of Gratiola officinalis lead to tumor cell death by apoptosis due to negative regulation of MCL-1 protein

Escape from cell death is one of the most prominent features of tumor cells and is closely related to the dysregulation of Bcl-2 family proteins. Among them, the anti-apoptotic protein Mcl-1 (myeloid cell leukaemia-1) acts as a master regulator of apoptosis in various human malignancies. The Mcl-1 -1 protein, whose main function is to protect tumor cells from apoptosis, is not the only product of the anti-apoptotic gene MCL1. On the contrary, another product of this gene, the shortened Mcl-1S protein, formed by alternative splicing, serves as a negative regulator of Mcl-1. Increased levels of Mcl-1S lead to inhibition of apoptosis-protective Mcl-1 and, consequently, tumor cell death by apoptosis (Senichkin, 2018). Mcl-1 inhibitors are currently being developed, which opens new perspectives to fight the hitherto untreatable addiction of cancer cells.