Antitumor efficacy of reticulol from Streptoverticillium against the lung metastasis model B16F10 melanoma. Lung metastasis inhibition by growth inhibition of melanoma.
Reticulol was isolated from the culture broth of the strain Streptoverticillium sp. NA-4803. Recticulol (M.W. 222.2) exhibited a potent in vitro cytotoxicity against A427, a human lung tumor cell line, and B16F10, a mouse melanoma cell line. In the trypan blue staining assay for B16F10 cells, the cell viability by reticulol treatment was significantly decreased in a dose-dependent manner. The in vivo assay for the lung metastasis-blocking effect showed that reticulol injected intravenously suppressed the increase in colonies on the lung in a dose-dependent manner. In addition, the survival rate of tumor-implanted mice treated with reticulol was closely associated with its antitumoral efficacy. Reticulol administered via the peritoneum of mice showed less metastasis inhibition than that injected intravenously. To demonstrate the mechanism for inhibition of metastasis, the inhibitory effect of reticulol for matrix metalloproteinase-2 or -9 involved in melanoma metastasis was investigated; however, they were not observed on zymogram gel. In addition, the antitumor efficacy of reticulol was not associated with cell cycle arrest or apoptosis. Therefore, it was inferred that reticulol known as a phosphodiesterase inhibitor directly inhibited the growth of B16F10 melanoma, showing necrotic response. These results suggest that reticulol protects its lung metastasis via the bloodstream by inhibiting the growth of B16F10 melanoma at the cellular level.
Lim
Dae-Seog
DS
Animal Resources Research Center, Konkuk University, Seoul, Korea. dslim99@hotmail.com
Kwak
Yi-Sub
YS
Kim
Jeong-Hwan
JH
Ko
Si-Hwan
SH
Yoon
Won-Ho
WH
Kim
Chang-Han
CH
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D049934:Isocoumarins; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000662:veterinary; D008545:Melanoma / Q000473:pathology* / Q000662:veterinary; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D009374:Neoplasms, Experimental
D003374:Coumarins; D049934:Isocoumarins; C010780:reticulol; D015105:3',5'-Cyclic-AMP Phosphodiesterases