Cytosolic JNK-dependent microtubule reassembly protects Jurkat leukemia cells from selenite-induced apoptosis

Microtubule, an important component of cytoskeleton, is mainly responsible for the process of intracellular organelle localization, vesicles transport or cell division [1], [2], [3]. Molecules that influence the dynamics of microtubule assembly/disassembly involve many antitumor drugs. Some studies have indicated that chemotherapeutic drugs, such as paclitaxel and colchicine, have obvious effects in treating tumors through inhibition of microtubule dynamics that leads to cyclins-dependent apoptotic cell death [4]. The regulatory mechanisms of these drugs were primarily related with directly binding with sulfhydryls of tubulin [5]. However, under some special conditions, disassembled microtubule could be reorganized, and these changes were important for the fate determination of tumor cells and needs to be fully studied [6].

Selenite in the super-nutritional range of dosage shows great potential in curing tumors. The anti-tumor function of selenite is often attributed to the induction of apoptosis and autophagy [7], and the exact underlying mechanisms were mainly related with the accumulation of reactive oxidant species and unfolded proteins [8]. Notably, some studies indicated that selenite could depolymerize microtubule through directly interacting with microtubule-associated proteins, and thereby induce tumor growth arrest and apoptosis in vitro and in vivo [9], [10], [11]. However, our previous study discovered in some cancer cells that microtubule could be re-assembled after long-term exposure to selenite. We found that alterations of some cyclins were closely related with this process; however, the exact mechanisms and the potential function of this phenomenon remained unknown [10]. A clear understanding of this phenomenon and the molecular mechanism involved is of great significance.

In the current study, we discovered for the first time that cytosolic JNK activation was the underlying molecular mechanism by which microtubule was re-assembled in long-term selenite-treated Jurkat cells. Inhibition of this process could enhance the anti-tumor activity of selenite in vitro. The phenomena observed in vitro had been further demonstrated in the animal model. This discovery is undoubtedly of great importance for the comprehensive understanding of the anti-tumor effects of selenite.

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