Development of small molecule Meis inhibitors for mitigating lung cancer growth

Meis1 is one of the transcription factors belonging TALE superclass transcription factors under MEINOX protein family. Meis2 and Meis3 also belong to same protein family and they all have similar protein sequences with 83 and 66 percent similarities with Meis1, respectively. Hematopoietic stem cells and cardiac regeneration are two fields in which Meis1 has role. In addition to HSC regulation and cardiac regeneration, dysregulated Meis1 is also correlated with tumorigenesis. In murine acute myeloid leukemia models, Meis1 was overexpressed and accelerated leukemogenesis. Apart from myeloid leukemia, Meis1 participates in other types of cancers such as acute lymphoid leukemia, prostate cancer, neuroblastomas, nephroblastomas, skin tumors, ovarian carcinomas as well as non small cell lung adenocarcinoma. Expression of metastatic cell adhesion molecule was activated by Meis1 in pancreatic cancer. Cell survival of malignant peripheral nerve sheath tumors was maintained by Meis1. Additionally, in neuroblastomas, nephroblastomas and ovarian carcinomas, Meis1 was upregulated. The behavior of Meis1 is different in HSCs, cardiac regeneration and different tumor types. However, the reason has not known yet. To find out a possible explanation, molecular mechanism needs to be enlightened. The purpose of this study was to define the effect of MEISi-2, small molecule MEIS inhibitor, on A549 non small cell lung cancer. We have observed that MEISi-2 treatment caused downregulation in cell proliferation and MEIS 1/2/3 gene expression, but upregulation in ROS and total apoptosis levels. Moreover, we have determined IC50 value as 10 uM. Taken together, MEISi-2 could be a potential therapeutic agent if the data obtained from this study could be supported with further studies.