Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential.
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.
Caltagirone
S
S
Department of Oncology and Neurosciences, G. D'Annunzio University, Chieti, Italy. caltagir@cmns.mnegri.it
Rossi
C
C
Poggi
A
A
Ranelletti
F O
FO
Natali
P G
PG
Brunetti
M
M
Aiello
F B
FB
Piantelli
M
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047310:Apigenin; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology* / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D005419:Flavonoids; D006131:Growth Inhibitors; D013267:Stilbenes; D013629:Tamoxifen; D047310:Apigenin; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; D003474:Curcumin; D000077185:Resveratrol