Administration of Spermidine and Eugenol Demonstrates Anti-Tumorigenic Efficacy on Metastatic SW620 and Primary Caco-2 Colorectal Cancer Spheroids

• Published in: International journal of molecular sciences Vol. 25; no. 24; p. 13362
• Main Authors: Dilloo, Silvia, Whittaker, Anne, Chang, Xinyue, D’Amen, Eros, Spisni, Enzo, Hrelia, Silvana, Angeloni, Cristina, Malaguti, Marco, Dinelli, Giovanni, Truzzi, Francesca
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2024
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Autophagy; Caco-2 Cells; Cancer therapies; Care and treatment; Cell cycle; Cell Movement - drug effects; Cell Proliferation - drug effects; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cytotoxicity; Development and progression; Drug dosages; Eugenol; Eugenol - pharmacology; Eugenol - therapeutic use; Health aspects; Human Development Index; Humans; Kinases; Medical research; Metastasis; Natural products; Oils & fats; Physiological aspects; Polyamines; Spermidine - pharmacology; Spheroids; Spheroids, Cellular - drug effects; Tumors; Italy; spermidine; Caco-2 spheroids; anti-tumorigenic efficacy; migration; SW620; apoptosis; eugenol; co-culture intestinal equivalents
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms252413362

The anti-cancer potential of eugenol (EUG) is well recognized, whereas that of spermidine (SPD) is subject to dispute and requires further research. The anti-tumorigenic potential of wheat germ SPD (150 µM) and clove EUG (100 µM), alone, in combination as SPD+EUG (50 µM + 100 µM) and, as a supplement (SUPPL; 0.6 µM SPD + 50 µM EUG), was investigated on both metastatic SW620 and primary Caco-2 colorectal cancer (CRC) spheroids. Compared to untreated controls, all treatments significantly reduced the vitality and spheroid area, increased the necrotic area, and induced apoptosis on both cell-type spheroids after 96 h, with a reduced migration evident in 2D (two-dimensional) cultures after 48 h. The comparable anti-CRC effects of the SPD+EUG and the SUPPL reflected a wide-range dose efficacy of SPD and EUG. It is of note that SPD+EUG induced a synergistic effect on the increased caspase-3 expression and reduced the migration percentage in SW620. In more physiologically relevant intestinal equivalents (healthy enterocytes [NCM460], fibroblasts [L929], and monocytes [U937]) containing embedded SW620/Caco-2 spheroids, SPD+EUG administration significantly reduced the spheroid CEA marker and proliferation, whilst simultaneously increasing occludin, autophagy LC3-II expression, and monocyte differentiation, compared to the control models. Exogenous SPD, alone and in combination with EUG, displayed an anti-CRC potential on tumor growth and metastasis, and warrants further investigation.