Boldine Inhibits Mouse Mammary Carcinoma In Vivo and Human MCF-7 Breast Cancer Cells In Vitro.
Boldine is an aporphine alkaloid widely consumed in the folk medicine of some regions. Its anticancer potential has been shown but not yet elucidated. We compared the antitumor effect of orally and parenterally applied boldine in mice bearing solid Ehrlich tumor. We also explored the effects of boldine on breast adenocarcinoma MCF-7 cellsin vitro. Repeated i. p. injections of 30, 60, or 90 mg boldine/kg, either alone or combined with doxorubicin, slowed tumor growthin vivo. The latter two doses also prolonged the post-therapeutic survival of the mice. When fed food supplemented with boldine at a dose of 90 mg/kg, the tumor-bearing mice survived significantly longer, but there was no effect on tumor size. Interestingly, continuous p. o. administration did not produce detectable levels of boldine in plasma or tissue samples, in contrast to high but short-lived concentrations after i. p. injections. There was neither antagonism nor synergism between boldine and doxorubicin, except a possible synergism of i. p. boldine 90 mg/kg combined with doxorubicin when compared with doxorubicin alone.Boldine was cytotoxic to MCF-7 cells and reduced their viability and proliferationin vitro. Exposure to boldine decreased bromodeoxyuridine incorporation and histone H3 phosphorylation but did not induce apoptosis. Boldine treatment resulted in p38, ERK, and JNK activation in the mitogen-activated protein kinase pathway in a dose-dependent manner. Since bioavailability in mice seems to be different from that reported in rats, pharmacokinetic studies in humans are needed to evaluate the role of boldine in the beneficial effects ofBoldoinfusions.
Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Pavel
P
Tomšík
Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Stanislav
S
Mičuda
Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Darina
D
Muthná
Computer Technology Center, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Eva
E
Čermáková
Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Radim
R
Havelek
Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Emil
E
Rudolf
Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Miloš
M
Hroch
Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Zuzana
Z
Kadová
Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Martina
M
Řezáčová
Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Jana
J
Ćmielová
Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Pavel
P
Živný
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001060:Aporphines / Q000494:pharmacology / Q000627:therapeutic use*; D004317:Doxorubicin; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008517:Phytotherapy
D000975:Antioxidants; D001060:Aporphines; D004317:Doxorubicin; C011686:boldine