CLC number:
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2023-05-16
Cited: 0
Clicked: 1310
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. 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[J]. Journal of Zhejiang University Science B, 2023, 24(5): 442-454.
@article{title="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, Shunnan YAO, Anqi LI, Haoguang CHEN, Enfan ZHANG, Liqin CAO, Jinna ZHANG, Yifan HOU, Zhenfeng DAI, Jing CHEN, Xi HUANG, Li YANG, Zhen CAI",
journal="Journal of Zhejiang University Science B",
volume="24",
number="5",
pages="442-454",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200465"
}
%0 Journal Article
%T 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
%A Wen CAO
%A Shunnan YAO
%A Anqi LI
%A Haoguang CHEN
%A Enfan ZHANG
%A Liqin CAO
%A Jinna ZHANG
%A Yifan HOU
%A Zhenfeng DAI
%A Jing CHEN
%A Xi HUANG
%A Li YANG
%A Zhen CAI
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 5
%P 442-454
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200465
TY - JOUR
T1 - 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
A1 - Wen CAO
A1 - Shunnan YAO
A1 - Anqi LI
A1 - Haoguang CHEN
A1 - Enfan ZHANG
A1 - Liqin CAO
A1 - Jinna ZHANG
A1 - Yifan HOU
A1 - Zhenfeng DAI
A1 - Jing CHEN
A1 - Xi HUANG
A1 - Li YANG
A1 - Zhen CAI
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 5
SP - 442
EP - 454
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200465
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.
[1]AndersonKC, 2016. Progress and paradigms in multiple myeloma. Clin Cancer Res, 22(22):5419-5427.
[2]ArgyriouAA, IconomouG, KalofonosHP, 2008. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood, 112(5):1593-1599.
[3]BassAKA, El-ZoghbiMS, NageebESM, et al., 2021. Comprehensive review for anticancer hybridized multitargeting HDAC inhibitors. Eur J Med Chem, 209:112904.
[4]HarbeckN, Penault-LlorcaF, CortesJ, et al., 2019. Breast cancer. Nat Rev Dis Primers, 5:66.
[5]HeJS, ChenQX, GuHY, et al., 2018. Therapeutic effects of the novel subtype-selective histone deacetylase inhibitor chidamide on myeloma-associated bone disease. Haematologica, 103(8):1369-1379.
[6]HuangX, CaoW, YaoSN, et al., 2022. NEDD4L binds the proteasome and promotes autophagy and bortezomib sensitivity in multiple myeloma. Cell Death Dis, 13(3):197.
[7]JiMY, LiZL, LinZH, et al., 2018. Antitumor activity of the novel HDAC inhibitor CUDC-101 combined with gemcitabine in pancreatic cancer. Am J Cancer Res, 8(12):2402-2418.
[8]JiangWQ, FuFF, LiYX, et al., 2012. Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 13(9):663-675.
[9]JoshuaDE, BryantC, DixC, et al., 2019. Biology and therapy of multiple myeloma. Med J Aust, 210(8):375-380.
[10]KikuchiS, SuzukiR, OhguchiH, et al., 2015. Class IIa HDAC inhibition enhances ER stress-mediated cell death in multiple myeloma. Leukemia, 29(9):1918-1927.
[11]KumarSK, RajkumarV, KyleRA, et al., 2017. Multiple myeloma. Nat Rev Dis Primers, 3:17046.
[12]KumarSK, HarrisonSJ, CavoM, et al., 2020. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol, 21(12):1630-1642.
[13]LiHY, CuiRH, JiMY, et al., 2021. CUDC-101 enhances the chemosensitivity of gemcitabine-treated lymphoma cells. Leuk Res, 106:106575.
[14]LiYH, YuanJ, 2021. Role of deubiquitinating enzymes in DNA double-strand break repair. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(1):63-72.
[15]LiangL, HeYJ, WangHQ, et al., 2020. The Wee1 kinase inhibitor MK1775 suppresses cell growth, attenuates stemness and synergises with bortezomib in multiple myeloma. Br J Haematol, 191(1):62-76.
[16]LuoHM, ZhangD, WangFF, et al., 2021. ALCAM-EGFR interaction regulates myelomagenesis. Blood Adv, 5(23):5269-5282.
[17]MahtoukK, HoseD, RèmeT, et al., 2005. Expression of EGF-family receptors and amphiregulin in multiple myeloma. Amphiregulin is a growth factor for myeloma cells. Oncogene, 24(21):3512-3524.
[18]MatthewsHK, BertoliC, de BruinRAM, 2022. Cell cycle control in cancer. Nat Rev Mol Cell Biol, 23(1):74-88.
[19]MinamiJ, SuzukiR, MazitschekR, et al., 2014. Histone deacetylase 3 as a novel therapeutic target in multiple myeloma. Leukemia, 28(3):680-689.
[20]ShimizuT, LorussoPM, PapadopoulosKP, et al., 2014. Phase I first-in-human study of CUDC-101, a multitargeted inhibitor of HDACs, EGFR, and HER2 in patients with advanced solid tumors. Clin Cancer Res, 20(19):5032-5040.
[21]VallabhapurapuSD, NoothiSK, PullumDA, et al., 2015. Transcriptional repression by the HDAC4-RelB-p52 complex regulates multiple myeloma survival and growth. Nat Commun, 6:8428.
[22]van de Donk NWCJ, PawlynC, YongKL, 2021. Multiple myeloma. Lancet, 397(10272):410-427.
[23]von TresckowB, BoellB, EichenauerD, et al., 2014. Anti-epidermal growth factor receptor antibody cetuximab in refractory or relapsed multiple myeloma: a phase II prospective clinical trial. Leuk Lymphoma, 55(3):695-697.
[24]Wallington-BeddoeCT, Sobieraj-TeagueM, KussBJ, et al., 2018. Resistance to proteasome inhibitors and other targeted therapies in myeloma. Br J Haematol, 182(1):11-28.
[25]WangJ, PursellNW, SamsonMES, et al., 2013. Potential advantages of CUDC-101, a multitargeted HDAC, EGFR, and HER2 inhibitor, in treating drug resistance and preventing cancer cell migration and invasion. Mol Cancer Ther, 12(6):925-936.
[26]WuSG, ShihJY, 2018. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer, 17:38.
[27]ZhangLS, BoufraqechM, LakeR, et al., 2016. Carfilzomib potentiates CUDC-101-induced apoptosis in anaplastic thyroid cancer. Oncotarget, 7(13):16517-16528.
[28]ZhangMN, ZhangLX, HeiRX, et al., 2021. CDK inhibitors in cancer therapy, an overview of recent development. Am J Cancer Res, 11(5):1913-1935.
[29]ZhangTZ, MaD, WeiDN, et al., 2020. CUDC-101 overcomes arsenic trioxide resistance via caspase-dependent promyelocytic leukemia-retinoic acid receptor alpha degradation in acute promyelocytic leukemia. Anticancer Drugs, 31(2):158-168.
[30]ZhouZL, van der JeughtK, FangYZ, et al., 2021. An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity. Nat Biomed Eng, 5(11):1320-1335.
Open peer comments: Debate/Discuss/Question/Opinion
<1>