Ketamine induces viability reduction and increased apoptosis in castration-resistant prostate cancer (CRPC) cells: an in-vitro study on PC-3 cell line

Yudhistira Pradnyan Kloping¹, Dimas Panca Andhika^2,3, Zakaria Aulia Rahman^2,3, Putu Kurnia Darma^2,3, Anthony Chi-Fai Ng⁴, Lukman Hakim^2,5,*
1 Faculty of Medicine, Universitas Pelita Harapan, Tangerang, Banten, Indonesia
2 Department of Urology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
3 Department of Urology, Universitas Airlangga Hospital, Surabaya, Indonesia
4 S.H. Ho Urology Centre, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
5 Department of Medicine, Faculty of Medicine and Health, Institut Teknologi Sepuluh Nopember, Surabaya, Indonesia
* Corresponding Author: Lukman Hakim. Email: email
(This article belongs to the Special Issue: Advances in Molecular Imaging and Targeted Therapies for Prostate Cancer)

Canadian Journal of Urology https://doi.org/10.32604/cju.2026.080627

Received 13 February 2026; Accepted 21 May 2026; Published online 18 June 2026

Download PDF

Abstract

Background: The use of N-methyl-D-aspartate (NMDA) receptor antagonists for anesthesia is common, but their potential for other purposes is currently being studied. Ketamine, the most prescribed NMDA blocker, is currently used to treat depression. The growing use of these drugs as outpatient treatments highlights their potential for other areas. Several studies suggest that NMDA receptors are expressed in malignant adenocarcinoma cells, including prostate cancer. Therefore, we aimed to evaluate the effects of ketamine on viability and apoptosis in castration-resistant prostate cancer (CRPC) cells. Methods: PC3 cell line, taken from a bone metastasis of a grade IV prostatic adenocarcinoma, was cultured in RPMI 1640 medium until ≥80% confluence. Cells were divided into treated and control groups. Ketamine was titrated (0.1024–200,000 nM) to determine the IC₅₀ level via CCK-8 assay. Apoptosis was assessed at four dose levels using Annexin V-based flow cytometry. Viability was calculated using the AAT Bioquest^® software. Apoptosis data were analyzed using one-way ANOVA and Tukey’s Honestly Significant Difference (HSD) post-hoc test in IBM^® SPSS^® software. Results: There is a dose-dependent effect of ketamine on the reduction of PC3 cell viability, with an IC₅₀ of 0.185 mM (R² = 0.96). Apoptosis rates at 0.045, 0.09, 0.18, and 0.36 mM of ketamine exposure were 14.21%, 21.17%, 39.46%, and 83.53%, respectively, compared to 9.5% in the control group. One-way ANOVA revealed significant rate differences (p < 0.001) between groups. The post-hoc analysis indicated a dose-dependent apoptotic effect with no significant differences between the 0.045 group and the control group. All other comparisons were statistically significant (p < 0.001). Conclusion: Ketamine exposure was associated with a dose-dependent reduction in viability and an increase in Annexin V-positive cells in PC3 CRPC cells in vitro. The findings suggest a potential biological effect on viability and apoptosis; further mechanistic and in vivo studies are required before establishing clinical relevance.