Affiliation: Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan.
Patients with malignant gliomas have poor prognoses, and the majority of the patients have local tumor recurrence after various treatments including surgery, radiotherapy, and chemotherapy. Thus it is mandatory to develop better therapies for treatment of these malignant brain tumors. Tetrandrine, a bisbenzylisoquinoline alkaloid, has antitumor effects against some cancers. Tetrandrine affects the cell cycle, production of reactive oxygen species, mitogen-activated protein kinase activity, and reverses multidrug resistance in various cancer cells. Since tetrandrine is a highly lipid-soluble and hydrophobic molecule with a low molecular weight, it may cross the blood brain barrier; thus, it could be used for the treatment of gliomas. Tetrandrine inhibits the large-conductance, calcium-activated potassium (BK) channels and the expression of BK channel has a positive correlation with tumor malignancy grade in human gliomas. Furthermore, tetrandrine also exerts cytotoxic effects, and induces apoptosis and radiosensitization in glioma cells by elimination of radiation-induced cell cycle perturbation. It also has anti-angiogenesis effects in gliomas, and exerts an antitumor effect on subcutaneous and intracerebral gliomas. Tetrandrine is a radiosensitizer and also a multidrug resistance reversing agent. Tetrandrine can probably be combined with radiotherapy or other chemotherapeutic agents to treat gliomas. Nonetheless, it is important to determine the balance between the safety and efficacy of tetrandrine in patients with malignant gliomas before any clinical application.