Open Access

ARTICLE

C-Phycocyanin–Cisplatin Combination Targeting Redox Balance for Enhanced Efficacy Against Glioblastoma Cells

Rym Akrout¹, Ludovic Leloup², Khouloud Ayed¹, Fabrice Parat², Sami Zekri^3,4, Wassim Y. Almawi¹, Rahma Boughriba¹, Hanen Attia¹, Olfa Masmoudi-Kouki⁴, Hervé Kovacic^2,*, Asma Gati^1,*

1 Laboratory of Genetics Immunology and Human Pathology, Biology Department, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, 2092, Tunisia
2 Faculté des Sciences Médicales et Paramédicales, Institut de NeuroPhysiopathologie (INP), UMR 7051, CNRS, Aix Marseille Université, Marseille, 13005, France
3 Confocal Microscopy Unit, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, 1007, Tunisia
4 Laboratory of Neurophysiology, Cellular Physiopathology and Biomolecules Valorisation, LR18ES03, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, 2092, Tunisia

* Corresponding Authors: Hervé Kovacic. Email: ; Asma Gati. Email:

(This article belongs to the Special Issue: Mechanisms of Reactive Oxygen Species Modulation in Cancer Therapy)

Oncology Research 2025, 33(12), 3887-3906. https://doi.org/10.32604/or.2025.070729

Received 22 July 2025; Accepted 22 September 2025; Issue published 27 November 2025

Abstract

Objectives: Cisplatin (CDDP) therapy for glioblastoma (GBM) is linked with several limitations, which include poor penetration of the blood-brain barrier (BBB), systemic toxicity, and the development of drug resistance mechanisms implicating oxidative stress dysregulation and compromised apoptotic pathways. This study evaluates C-Phycocyanin (C-PC) as a potential adjuvant to enhance CDDP efficacy by modulating redox balance and apoptosis. Methods: GBM cells (U87 and U87-EGFRvIII) were treated with CDDP, C-PC, or their combination. Cell viability was assessed by MTT assay; apoptosis was evaluated by DAPI staining and Western blot analysis of cleaved Caspase-3 and poly (ADP-ribose) polymerase (PARP). Both intracellular and extracellular reactive oxygen species (ROS) were measured using 2^′,7^′-dichlorodihydrofluorescein diacetate (DCF-DA) fluorescence and lucigenin chemiluminescence, respectively. Catalase activity was quantified via hydrogen peroxide (H₂O₂) decomposition assay, and manganese superoxide dismutase (MnSOD) expression by Western blot. Results: C-PC selectively decreased U87 GBM cell viability while sparing normal cells. C-PC enhanced CDDP cytotoxicity, reducing viability to 26.5% vs. 53.2% for CDDP alone. This effect correlated with increased apoptosis, evidenced by DNA fragmentation and higher cleaved caspase-3 and PARP levels. Combined treatment lowered ROS below survival thresholds while upregulating MnSOD and catalase activity. In U87-EGFRvIII cells, CDDP reduced viability modestly (85.2%), C-PC alone decreased viability significantly (51.5%) and induced cell death, but the combination did not further increase apoptosis. Here, C-PC’s pro-apoptotic effects, alone or with CDDP, were also associated with reduced oxidative stress in cells. Conclusion: We demonstrate that C-PC enhances CDDP cytotoxicity in sensitive U87 cells by promoting apoptosis and modulating ROS, suggesting potential for improved therapeutic efficacy with reduced systemic toxicity. Compared to the combination, C-PC monotherapy achieves superior cytotoxicity in CDDP-resistant U87-EGFRvIII cells, underscoring its potential as a standalone therapeutic approach for chemotherapy-resistant glioblastoma subtypes.

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