Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential

• Published in: International journal of cancer Vol. 87; no. 4; pp. 595 - 600
• Main Authors: Caltagirone, Sara, Rossi, Cosmo, Poggi, Andreina, Ranelletti, Franco O., Natali, Pier Giorgio, Brunetti, Mauro, Aiello, Francesca B., Piantelli, Mauro
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 15-08-2000; Wiley-Liss
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; Anticarcinogenic Agents - therapeutic use; Antineoplastic agents; Apigenin; Biological and medical sciences; Catechin - analogs & derivatives; Catechin - pharmacology; Catechin - therapeutic use; Cell Division - drug effects; Chemotherapy; Curcumin - pharmacology; Curcumin - therapeutic use; Female; Flavonoids - pharmacology; Flavonoids - therapeutic use; Growth Inhibitors - pharmacology; Growth Inhibitors - therapeutic use; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Medical sciences; Melanoma, Experimental - pathology; Melanoma, Experimental - prevention & control; Melanoma, Experimental - secondary; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness; Neoplasm Transplantation; Pharmacology. Drug treatments; Quercetin - pharmacology; Quercetin - therapeutic use; Resveratrol; Stilbenes - pharmacology; Stilbenes - therapeutic use; Tamoxifen - pharmacology; Tamoxifen - therapeutic use; Tumor Cells, Cultured; Antineoplastic agent; Animal model; Rodentia; Melanoma; Antimetastatic agent; Malignant tumor; Metastasis; Flavonoid; In vitro; Biological activity; Bronchopulmonary; In vivo; Vertebrata; Chemotherapy; Polyphenol; Mammalia; Treatment; Mouse; Apigenin; Animal; Established cell line; Quercetin
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/1097-0215(20000815)87:4<595::AID-IJC21>3.0.CO;2-5

Flavonoids are a class of polyphenolic compounds widely distributed in the plant kingdom, which display a variety of biological activities, including chemoprevention and tumor growth inhibition. Our aim was to investigate the effects of several polyphenols on the growth and metastatic potential of B16‐BL6 melanoma cells in vivo. Intraperitoneal administration of quercetin, apigenin, (–)‐epigallocathechin‐3‐gallate (EGCG), resveratrol, and the anti‐estrogen tamoxifen, at the time of i.m. injection of B16‐BL6 cells into syngeneic mice, resulted in a significant, dose‐dependent delay of tumor growth, without toxicity. The relative descending order of potency was EGCG > apigenin = quercetin = tamoxifen > resveratrol > control. Furthermore, polyphenols significantly potentiated the inhibitory effect of a non‐toxic dose of cisplatin. When tested for the ability to inhibit lung colonization, quercetin, apigenin, and tamoxifen (but not EGCG or resveratrol) significantly decreased the number of B16‐BL6 colonies in the lungs in a dose‐dependent manner, with quercetin and apigenin being more effective than tamoxifen. Interestingly, quercetin, apigenin, and tamoxifen (but not EGCG or resveratrol) significantly decreased the invasion of B16‐BL6 cells in vitro, with quercetin and apigenin being more effective than tamoxifen. This suggests that anti‐invasive activity is one of the mechanisms underlying inhibition of lung colonization by quercetin and apigenin. In conclusion, quercetin and apigenin inhibit melanoma growth and invasive and metastatic potential; therefore, they may constitute a valuable tool in the combination therapy of metastatic melanoma. Int. J. Cancer 87:595–600, 2000. © 2000 Wiley‐Liss, Inc.