Ascorbic acid and 6-deoxy-6-chloro-ascorbic acid: potential anticancer drugs.
The role of ascorbic acid (AA) in prevention and suppression of carcinogenesis has been known for a long time. It was also found that AA may inhibit the growth of some tumor cells in vitro and in vivo. We examined the influence of ascorbic acid and 6-chloro-6-deoxy ascorbic acid (6-Cl-AA) on the growth of various human cell lines: lung fibroblasts (Hef), ovarian adenocarcinoma (OVCAR), colon adenocarcinoma (HT-29), laryngeal carcinoma (HEp2) cells, HEp2 cells resistant to vincristine (HEp2VA3), cervical carcinoma (HeLa) cells, HeLa cells resistant to cisplatin (Helacis), breast adenocarcinoma (SK-BR-3) cells, and SK-BR-3 resistant to doxorubicin (SK-BR-3-Dox), as well as mouse fibroblasts L929, mouse melanoma B16 (Mel B16) cells and Chinese hamster fibroblasts (V79). Both drugs arrested the growth of: HeLa, SK-BR-3, SK-BR-3-Dox, L929, and Mel B16 cells, but did not influence the growth of others: Hef, OVCAR, HEp2, HEp2VA3 and V79. 6-Cl-AA suppressed more the proliferation of HeLacis, SK-BR-3-Dox and Mel B16 cells than AA, while AA was active only against HT-29 cells. Inhibitory effect of 6-Cl-AA was confirmed by the in vivo experiments on solid melanoma B16 tumors. Our results indicate that AA and 6-Cl-AA could serve as potential antitumor agents, especially against some tumor cells resistant to chemotherapy.
Osmak
M
M
Department of Molecular Medicine, Ruder Bosković Institute, Zagreb, Croatia.
Kovacek
I
I
Ljubenkov
I
I
Spaventi
R
R
Eckert-Maksić
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; C089412:6-chloro-6-deoxyascorbic acid; D001205:Ascorbic Acid