Fusaric acid inhibits proliferation and induces apoptosis through triggering endoplasmic reticulum stress in MCF-7 human breast cancer cells.

Breast cancer has replaced lung cancer to be the leading cancer in the world. Currently, chemotherapy is still the major method for breast cancer therapy, but its overall effect remains unsatisfactory. Fusaric acid (FSA), a mycotoxin derived from fusarium species, has shown potency against the proliferation of several types of cancer cells, but its effect on breast cancer cells has not been examined. Therefore, we explored the possible effect of FSA on the proliferation of MCF-7 human breast cancer cells and uncovered the underlying mechanism in the present study. Our results showed that FSA has a strong anti-proliferative effect on MCF-7 cells through inducing ROS production, apoptosis and arresting cell cycle at G2/M transition phase. Additionally, FSA triggers endoplasmic reticulum (ER) stress in the cells. Notably, the cell cycle arrest and apoptosis inducing effect of FSA can be attenuated by ER stress inhibitor, tauroursodeoxycholic acid. Our study provide evidence that FSA is a potent proliferation inhibition and apoptosis inducing agent against human breast cancer cells, and the possible mechanism involves the activation of ER stress signaling pathways. Our study may highlight that FSA is promising for the future in vivo study and development of potential agent for breast cancer therapy.

Fusaric acid: a novel agent and mechanism to treat HNSCC.

OBJECTIVE: A new class of carboxylic acids has tumoricidal activity for head and neck squamous cell cancer (HNSCC). Fusaric acid (FA) can chelate divalent cations, especially zinc, and inactivate zinc finger proteins involved in DNA repair and protein synthesis. METHODS: 2 squamous carcinoma lines were utilized for in vitro and in vivo portions of this study. Cell counting and flow cytometry were used to analyze cells in culture in treatment and control groups over 96 hours. HNSCC subcutaneous implants were created in treatment and control groups of BALB-c nude mice (N = 30). RESULTS: In vitro studies demonstrated significant changes in cell numbers and cell cycle. In vivo studies of daily intralesional therapy for 1 month also showed reduced onset of growth and overall growth compared to controls. CONCLUSION: FA appears to have a tumoristatic/tumoricidal effect on HNSCC. Further nude mice studies are needed to optimize dosing and administration regimens for FA in anticipation of clinical trials.

Effect of fusaric acid (a dopamine beta-hydroxylase inhibitor) on phaeochromocytoma.

Fusaric acid, an inhibitor of dopamine beta-hydroxylase, which converts dopamine to noradrenaline, lowered the blood pressure and induced a subjective improvement in patients with phaeochromocytoma. These effects may be due either to an impairment of catecholamine biosynthesis or to a direct action on the blood vessels. The use of this drug in the treatment of patients with inoperable malignant phaeochromocytoma or neuroblastoma may improve symptoms and prolong survival.

NIH conference. Dopamine- -hydroxylase. Basic and clinical studies.

Dopamine-beta-hydroxylase, the enzyme responsible for conversion of dopamine to norepinephrine, is released along with catecholamines from the adrenal medulla and from sympathetic nerve endings. The properties and mechanisms of the enzyme's action are discussed and its distribution described. Dopamine-beta-hydroxylase is a valuable indicator of exocytosis as a mechanism for neurotransmitter release. The enzyme is present in plasma, but its levels vary widely between individuals. This variation seems to be related more to genetic factors than to sympathetic nerve activity. Abnormally high or low plasma levels are associated with several diseases. However, the relation of these levels to disease pathogenesis rather than to genetic determinants is unclear. Levels of the enzyme are elevated in patients with pheochromocytoma and decline after removal of the tumor. Dopamine-beta-hydroxylase levels seem to be normal in hypertensive patients. Inhibition of dopamine-beta-hydroxylase provides a useful pharmacologic approach to evaluating the role of norepinephrine in psychiatric disorders.