Blockade of JAK2/STAT3 intensifies the anti-tumor activity of arsenic trioxide in acute myeloid leukemia cells: Novel synergistic mechanism via the mediation of reactive oxygen species.

European Journal of Pharmacology
Yashar MesbahiArdeshir Ghavamzadeh

Abstract

Reactive oxygen species (ROS) are essential mediators of crucial cellular processes including apoptosis, proliferation, survival and cell cycle. Their regulatory role in cancer progression has seen in different human malignancies such as acute myeloid leukemia (AML). AML patients suffer from high resistance of the tumors against routine therapeutics including ATO. ATO enhance reactive oxygen species levels and induce apoptosis and suppresses proliferation in AML cells. However, some pathways such as JAK2/STAT3 ease anti-tumor activity of ATO by reducing reactive oxygen species amount and protecting the cell from apoptosis. In the present study, we use ruxolitinib (potent JAK2 inhibitor) to increase the sensitivity of AML cells to ATO treatment. We test, the effect of this combination on metabolic activity, proliferation, colony formation, cell cycle distribution, apoptosis, oxidative stress and DNA damage. Our results showed that combination of ATO with ruxolitinib synergistically reduced metabolic activity, proliferation and survival of AML cell lines. This combination induced G1/S cell cycle arrest because of reactive oxygen species elevation and GSH reduction. Besides, enhancement of reactive oxygen species increased apoptos...Continue Reading

Citations

Jan 9, 2020·Stem Cell Reviews and Reports·Azin SamimiElahe Khodadi
Aug 21, 2021·Chinese Medical Journal·Chao DongLi-Jun Zhang

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