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Targeting of mTORC1/2 by dihydroevocarpine induces cytotoxicity in acute myeloid leukemia
Author(s) -
Zhang Silin,
Xiong Yunhe,
Zhang Yixian,
Zhao Hongmei
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27974
Subject(s) - myeloid leukemia , mtorc1 , cancer research , pi3k/akt/mtor pathway , cytotoxicity , tumor microenvironment , bone marrow , apoptosis , leukemia , chemistry , myeloid , biology , medicine , immunology , in vitro , tumor cells , biochemistry
Interactions between the tumor cells and bone marrow (BM) microenvironment promote survival, growth, and chemoresistance of acute myeloid leukemia (AML). The mTOR pathway plays a key role in mediating the AML‐BM microenvironment interactions. Here, we report the anti‐AML activity of a natural monomer extracted from the Chinese medicinal herb Evodia rutaecarpa, dihydroevocarpine. Our results showed that dihydroevocarpine‐induced cytotoxicity, apoptosis, and G0/G1 arrest in AML cells, and inhibited the tumor growth in an AML xenograft model. Importantly, our study revealed that the dihydroevocarpine treatment inhibited the mTOR pathway via suppressing the mTORC1/2 activity, and thus overcame the protective effect of the BM microenvironment on AML cells. Taken together, our findings suggest that dihydroevocarpine could be used as a potential anti‐AML agent alone or a therapeutic adjunct in AML therapy, particularly in the presence of the BM microenvironment.