Investigating The Impact Of Homoharringtonine On K562 Cell Viability And ER Stress Pathways

¹ Graduate School, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China;
² School of Healthy Science and Engineering, University of Shanghai for Science and Technology, 200093 Shanghai, China;
³ Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
⁴ Collaborative innovation Center for Biomedicine of Shanghai University of Medicine & Health Sciences, 201318 Shanghai, China.

^* Corresponding author: zhouzl@sumhs.edu.cn

Abstract

This study investigated the effects of Homoharringtonine (HHT) on K562 cell proliferation and endoplasmic reticulum (ER) stress. The inhibitory effect of HHT was assessed using the CCK-8 assay to calculate IC50 values. Flow cytometry evaluated cell cycle distribution post-HHT exposure, while Proteostat dye assessed protein aggregation. Expression levels of XBP1s and related markers (BIP, CHOP, IRE1α) were measured to analyze ER stress. Results indicated that HHT significantly reduced K562 cell viability, yielding an IC50 value of 28.53 nM. HHT treatment caused cell accumulation in the G0/G1 phase, indicating cell cycle arrest. It also activated ER stress pathways, leading to increased levels of XBP1s, BIP, and CHOP. The combination of HHT with the ER stress inhibitor 4PBA alleviated HHT-induced ER stress, enhancing its anti-tumor effects. This study demonstrates that HHT inhibits K562 cell proliferation while activating ER stress pathways, suggesting that modulating ER stress may enhance its therapeutic efficacy in myeloid leukemia. Further research is required to elucidate the underlying mechanisms.