IMR Press / FBL / Volume 29 / Issue 4 / DOI: 10.31083/j.fbl2904132
Open Access Original Research
Antipsychotic Zuclopenthixol Inhibits Melanoma Growth and Brain Metastasis by Inducing Apoptosis and Cell Cycle Arrest
Show Less
1 Department of Burn and Plastic Surgery, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China
2 Department of Rehabilitation Medicine, Rehabilitation Medical Center, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
3 Department of Dermatovenereology, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China
4 Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China
*Correspondence: (Jie Zhang)
Front. Biosci. (Landmark Ed) 2024, 29(4), 132;
Submitted: 15 December 2023 | Revised: 5 February 2024 | Accepted: 7 March 2024 | Published: 29 March 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: The incidence of melanoma brain metastasis (MBM) is high and significantly compromises patient survival and quality of life. Effective treatment of MBM is made difficult by the blood-brain barrier (BBB), since it restricts the entry of drugs into the brain. Certain anti-psychotic drugs able to cross the BBB have demonstrated efficacy in suppressing brain metastasis in preclinical studies. However, the activity of zuclopenthixol against MBM is not yet clear. Methods: Cell viability assays were employed to investigate the potential of zuclopenthixol in the treatment of MBM. Subsequently, the mechanism of action was investigated by RNA-sequencing (RNAseq), flow cytometry-based cell cycle and apoptosis assays, protein expression analysis, and autophagy flux detection. Additionally, the efficacy of zuclopenthixol against tumor growth was investigated in vivo, including MBM models. Results: Zuclopenthixol inhibited the proliferation of various melanoma cell lines at minimal doses by causing cell cycle arrest in the G0/G1 phase and mitochondrial-mediated intrinsic apoptosis. Zuclopenthixol also induced cytoprotective autophagy, and inhibition of autophagy enhanced the anti-melanoma effects of zuclopenthixol. Furthermore, zuclopenthixol inhibited the growth of human melanoma tumors in nude mice, as well as the growth of intracranial metastases in a mouse model of MBM. Conclusions: These results demonstrate that zuclopenthixol has significant potential as an effective therapeutic agent for MBM.

cell cycle arrest
brain metastasis
81703083/National Natural Science Foundation of China
cstc20jcyj-msxmx0110/General Project of Chongqing Natural Science Foundation
Fig. 1.
Back to top