Rym Akrout, Khouloud Ayed, Hela Mrizak, Ludovic Leloup, Orace Mathieu Kenou, Fidèle Fassinou, Dhouha Bacha, Rahma Boughriba, Hanène Attia, Hervé Kovacic, Wassim Y. Almawi, Asma Gati
Marine-derived natural products are increasingly recognized for their therapeutic potential in cancer and other chronic diseases. Despite significant advances, current cancer treatments remain challenged by toxicity, drug resistance, and limited survival benefits. Natural compounds offer promising alternatives due to their multi-target mechanisms and favorable safety profiles. Among them, Spirulina, a filamentous cyanobacterium, stands out for its rich composition and diverse biological activities. Its anticancer effects involve apoptosis induction via intrinsic and extrinsic pathways, cell cycle arrest at G1/S or G2/M phases, inhibition of angiogenesis through the VEGF/VEGFR2 axis, and suppression of epithelial-mesenchymal transition. These activities are mainly attributed to C-phycocyanin, allophycocyanin, phenolic compounds, and immunomodulatory polysaccharides. Spirulina also exhibits potent immunomodulatory effects by enhancing natural killer cell activity, promoting M1 macrophage polarization, and regulating Th1 and Th17 cytokine responses, highlighting its potential as both an immunotherapeutic and chemoprotective agent. Moreover, preclinical findings suggest it may reduce chemotherapy-associated side effects. However, translation into clinical therapy remains limited by low bioavailability, lack of standardized extracts, and scarce clinical evidence. This review summarizes current mechanistic and immunological insights and highlights the need for optimized formulations, defined dosing strategies, and well-designed clinical trials to validate Spirulina's potential in cancer treatment.