Boldine Inhibits Mouse Mammary Carcinoma In Vivo and Human MCF-7 Breast Cancer Cells In Vitro

Abstract

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 cells . Repeated i. p. injections of 30, 60, or 90 mg boldine/kg, either alone or combined with doxorubicin, slowed tumor growth. 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 proliferation . 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 of infusions.

Possible Therapeutics for Pseudomyxoma Peritonei: A Rare, Lethal, and the Least Investigated Disease

“…In a dosedependent manner, boldine treatment activated p38, extracellular signal-regulated kinase protein (ERK) and JNK in the mitogen-activated protein kinase pathway. 23 Boldine induced apoptosis in breast cancer cells, as indicated by an increased lactate dehydrogenase, increased membrane permeability, and DNA fragmentation. In addition, boldine induces cell-cycle arrest at G2/M phase.…”

“…21 Boldine interacts with the peroxisome proliferator-acitvated receptor (PPAR) response element and could modulate PPAR-responsive genes. 22 An in-vitro study 23 showed that boldine reduced the viability and proliferation of Michigan Cancer Foundation (MCF)-7 cells and was cytotoxic to them. It decreased bromodeoxyuridine incorporation and histone H3 phosphorylation, but did not induce apoptosis in this case.…”

Boldine Alkaloid: Holistic Overview on Potential Health Benefits and Medicinal Merits a comprehensive review

“…While another in vivo study against mouse mammary carcinoma showed that intra peritoneal injections of boldine repeatedly slowed tumor growth. In addition, in vitro study against human MCF-7 breast cancer cells revealed that boldine was cytotoxic to MCF-7 cells and reduced cell viability and proliferation [39].…”

Boldine protects against carbon tetrachloride‐induced chronic liver injury by regulating NF‐κB signaling pathway

“…[ 10 ] but its use has been expanded to treat rheumatoid arthritis, hypertension, diabetes mellitus and cancer for its numerous pharmacological properties. [ 11 ] Studies have reported that boldine exerts anti‐inflammatory, [ 12 ] antioxidant, [ 13 ] anticancer, [ 14 ] antidiabetic, [ 15 ] antipyretic, antiatherogenic, anticonvulsive, [ 16 ] neuroprotective, [ 17 ] nephroprotective, hepatoprotective and cytoprotective effects. [ 8 ] From the liver perspective, boldine has been shown to protect the liver against oxidative stress, cholestasis and drug‐induced liver injury in experimental studies.…”