Combination therapy with HSP90 inhibitors and piperlongumine promotes ROS-mediated ER stress in colon cancer cells
Chenyu Qiu, Xin Shen, Hui Lü, Yinghua Chen, Chenxin Xu, Peisen Zheng, Yiqun Xia, Junqi Wang, Yafei Zhang, Shaotang Li, Peng Zou, Ri Cui, Jundixia Chen
Abstract
Colon cancer is a major cause of cancer-related death. Despite recent improvements in the treatment of colon cancer, new strategies to improve the overall survival of patients are urgently needed. Heat shock protein 90 (HSP90) is widely recognized as a promising target for treating various cancers, including colon cancer. However, no HSP90 inhibitor has been approved for clinical use due to limited efficacy. In this study, we evaluated the antitumor activities of HSP90 inhibitors in combination with piperlongumine in colon cancer cells. We show that combination treatment with HSP90 inhibitors and piperlongumine displayed strong synergistic interaction in colon cancer cells. These agents synergize by promoting ER stress, JNK activation, and DNA damage. This process is fueled by oxidative stress, which is caused by the accumulation of reactive oxygen species. These studies nominated piperlongumine as a promising agent for HSP90 inhibitor-based combination therapy against colon cancer.