A polysaccharide from native Curcuma kwangsiensis and its mechanism of reversing MDSC-induced suppressive function

Abstract

A purified polysaccharide nCKAP-2 was prepared from Curcuma kwangsiensis and characterized. Structural analyses revealed that nCKAP-2 contains a high-branched arabinan composed of mono-substituted (O-5, 17.07 %) and di-substituted (O-2,5, 16.67 %) (1 → 3)-α-Araf residues. Bioactive test showed that nCKAP-2 significantly reversed the suppression function of myeloid-derived suppressor cells (MDSCs) on T cells. Further study revealed that treatment of MDSCs with nCKAP-2 could induce apoptotic cell death at the G0/G1 phase via the intrinsic pathway as suggested from the up-regulation of cleaved caspase 3 and 9, cleaved PARP, and Bax and the down-regulation of Bcl-xl. This apoptotic process was mainly mediated by the TLR4-NF-κB signaling pathway. Additionally, the down-regulation of ROS level of MDSCs after nCKAP-2 treatment involved in this process. Summarily, we explain how nCKAP-2 reverses the MDSC-induced suppressive function on T cells, and provide a scientific basis for the clinical application and development of C. kwangsiensis.