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Targeting of mTORC1/2 by dihydroevocarpine induces cytotoxicity in acute myeloid leukemia |
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| Authors: | Silin Zhang Yunhe Xiong Yixian Zhang Hongmei Zhao |
| Affiliation: | 1. Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, China Silin Zhang and Yunhe Xiong are co-first authors.;2. Urology Department, Renmin Hospital of Wuhan University, Wuhan, China Silin Zhang and Yunhe Xiong are co-first authors.;3. Department of Pediatrics, Huai'an Affiliated Hospital of Xuzhou Medical University, The Second People's Hospital of Huai'an, Huai'an, China;4. Department of Pathology, Huaiyin Hospital of Huai'an city, Huai'an, China |
| Abstract: | 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. |
| Keywords: | acute myeloid leukemia (AML) bone marrow (BM) microenvironment dihydroevocarpine mTOR complex 1 (mTORC1) mTOR complex 2 (mTORC2) |