CUDC-101 as a dual-target inhibitor of EGFR and HDAC enhances the anti-myeloma effects of bortezomib by regulating G2/M cell cycle arrest.

Wen Cao; Shunnan Yao; Anqi LI; Haoguang Chen; Enfan Zhang; Liqin Cao; Jinna Zhang; Yifan Hou; Zhenfeng Dai; Jing Chen; Xi Huang; Li Yang; Zhen Cai

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CUDC-101 as a dual-target inhibitor of EGFR and HDAC enhances the anti-myeloma effects of bortezomib by regulating G2/M cell cycle arrest.

Author: Wen CAO ¹ ; Shunnan YAO ² ; Anqi LI ¹ ; Haoguang CHEN ¹ ; Enfan ZHANG ¹ ; Liqin CAO ¹ ; Jinna ZHANG ¹ ; Yifan HOU ¹ ; Zhenfeng DAI ¹ ; Jing CHEN ¹ ; Xi HUANG ¹ ; Li YANG ³ ; Zhen CAI ⁴
Author Information

1. Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
2. School of Medicine, Zhejiang University, Hangzhou 310058, China.
3. Institute of Hematology, Zhejiang University, Hangzhou 310058, China. caiz@zju.edu.cn, liyanghz@zju.edu.cn.
4. Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China. caiz@zju.edu.cn.
Publication Type:Journal Article
Keywords: Bortezomib; CUDC-101; Cell cycle; Epidermal growth factor receptor (EGFR); Multiple myeloma
MeSH: Humans; Antineoplastic Agents/therapeutic use*; Apoptosis; Bortezomib/pharmacology*; Cell Line, Tumor; Cell Proliferation; ErbB Receptors/antagonists & inhibitors*; G2 Phase Cell Cycle Checkpoints; Histone Deacetylase Inhibitors/pharmacology*; Histone Deacetylases/metabolism*; M Cells; Multiple Myeloma/drug therapy*
From: Journal of Zhejiang University. Science. B 2023;24(5):442-454
CountryChina
Language:English
Abstract: CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.