@Article{or.2025.070729,
AUTHOR = {Rym Akrout, Ludovic Leloup, Khouloud Ayed, Fabrice Parat, Sami Zekri, Wassim Y. Almawi, Rahma Boughriba, Hanen Attia, Olfa Masmoudi-Kouki, Hervé Kovacic, Asma Gati},
TITLE = {C-Phycocyanin–Cisplatin Combination Targeting Redox Balance for Enhanced Efficacy Against Glioblastoma Cells},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {12},
PAGES = {3887--3906},
URL = {http://www.techscience.com/or/v33n12/64645},
ISSN = {1555-3906},
ABSTRACT = { <b>Objectives:</b> 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. <b>Methods:</b> 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<sup>′</sup>,7<sup>′</sup>-dichlorodihydrofluorescein diacetate (DCF-DA) fluorescence and lucigenin chemiluminescence, respectively. Catalase activity was quantified via hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) decomposition assay, and manganese superoxide dismutase (MnSOD) expression by Western blot. <b>Results:</b> 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. <b>Conclusion:</b> 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.},
DOI = {10.32604/or.2025.070729}
}