Potent carotenoid astaxanthin expands the anti-cancer activity of cisplatin in human prostate cancer cells

• Published in: Journal of natural medicines 2023-06, Vol.77 (3), p.572-583
• Main Authors: Erzurumlu, Yalcin, Catakli, Deniz, Dogan, Hatice Kubra
• Format: Article
• Language: English
• Subjects: adjuvants; Angiogenesis; Anti-inflammatory agents; antineoplastic activity; antioxidants; Antitumor activity; Apoptosis; Astaxanthin; Biomedical and Life Sciences; Biomedicine; c-Myc protein; Carcinogenesis; Carotenoids; Cell death; Cisplatin; Complementary & Alternative Medicine; death; drug therapy; humans; Immunotherapy; Inflammation; lutein; Lycopene; mechanism of action; Medicinal Chemistry; Molecular modelling; Movement disorders; Myc protein; Neurodegenerative diseases; Original Paper; Parkinson's disease; Pharmacology/Toxicology; Pharmacy; Plant extracts; Plant Sciences; Prostate cancer; Prostate-specific antigen; prostatic neoplasms; Protein folding; proto-oncogenes; Radiation therapy; radiotherapy; synergism; unfolded protein response; Vascular endothelial growth factor; vascular endothelial growth factor A; Xanthophylls
• ISSN: 1340-3443; 1861-0293
• DOI: 10.1007/s11418-023-01701-1

Prostate cancer (PCa) is the second most common type of cancer and the sixth cause of death in men worldwide. Radiotherapy and immunotherapy are commonly used in treating PCa, but understanding the crosstalk mechanisms of carcinogenesis and new therapeutic approaches is essential for supporting poor diagnosis and existing therapies. Astaxanthin (ASX) is a member of the xanthophyll family that is an oxygenated derivative of carotenoids whose synthesis is in plant extracts from lycopene. ASX has protective effects on various diseases, such as Parkinson’s disease and cancer by showing potent antioxidant and anti-inflammatory properties. However, there is an ongoing need for a detailed investigation of the molecular mechanism of action to expand its therapeutic use. In the present study, we showed the new regulatory role of ASX in PCa cells by affecting the unfolded protein response (UPR) signaling, autophagic activity, epithelial–mesenchymal transition (EMT) and regulating the expression level of angiogenesis-related protein vascular endothelial growth factor A (VEGF-A), proto-oncogene c-Myc and prostate-specific antigen (PSA). Additionally, we determined that it exhibited synergistic action with cisplatin and significantly enhanced apoptotic cell death in PCa cells. Present findings suggest that ASX may be a potent adjuvant therapeutic option in PCa treatment when used alone or combined with chemotherapeutics. Graphical abstract Schematic illustration of the biochemical activity of astaxanthin and its combination with cisplatin.