Malignant gliomas are one of the more lethal forms of cancer. An estimated 18,000 new cases of brain and central nervous system tumors are diagnosed each year and approximately 13,000 people die of their disease in the United States alone . Those diagnosed with the most malignant form of astrocytoma (glioblastoma multiforme, GBM) have a dismal prognosis. The median survival rate of one year has remained essentially unchanged for a number of years despite aggressive treatment regimens that include surgery, radiation and chemotherapy. Complete surgical removal of the tumor is typically not achieved due to the infiltrative nature of these tumors and while radiation and chemotherapy kill the majority of the remaining tumor cells, the rapid recurrence of these tumors suggest the presence within the primary tumor of a subpopulation of cells intrinsically resistant to therapy and capable of survival and growth within the tumor bed following therapy [2, 3]. When these tumors recur, they are typically refractory to additional courses of the same therapies. Improvement in the survival and quality of life of glioma patients requires the design of new therapies or therapeutic combinations that are effective and preferably have fewer side effects than those presently available.
One promising new source of therapeutic agents has been discovered in plant secondary metabolites, irregularly occurring compounds that characterize certain plants or plant groups . Recent interest in these secondary metabolites has been focused upon their medicinal properties . For example, flavonoids are a large group of aromatic plant secondary metabolites that are produced in the plant for the purpose of protection from photosynthetic stress, reactive oxygen species (ROS), wounds and herbivores. Studies of flavonoids have produced the most compelling data for the antitumor activities of plant secondary metabolites in various types of cancers , and several flavonoids have been shown to inhibit cancer development while exhibiting antioxidant activities in various animal models [7–11]. Furthermore, some studies suggest that the most promising use of these compounds may be as an adjuvant to currently used therapies [12, 13].
Numerous cancer research studies have been conducted using traditional medicinal plants in an effort to discover new therapeutic agents that lack the toxic side effects associated with current chemotherapeutic agents. One of the more versatile plants used as a source of flavonoids is the root of the traditional Chinese medicinal herb Baikal skullcap (Scutellaria baicalensis), a member of the mint family . Traditionally, the dried roots of S. baicalensis were extracted and used in a Chinese herbal medicine "Huang Qin" to treat a variety of ailments , and Scutellaria baicalensis has remained an important herb in both Chinese and Japanese traditional prescriptions, such as "Xiao-Chai-Hu-Tang" which is used in the treatment of viral hepatitis and a variety of tumors [16–18]. Various flavonoids isolated from this traditional Chinese medicinal plant were shown to have antiandrogenic and growth inhibitory activity against prostate cancer cells in vitro and in vivo [19–26]. In addition, extracts and isolated flavonoids from this herb have been shown to relieve oxidative stress and immune dysfunction associated with the onset and progress of cancer . Studies have also demonstrated that flavonoids from S. baicalensis have the ability to arrest the cell cycle of tumor cell lines that are resistant to multiple chemotherapeutic drugs  and act as inhibitors of key steps necessary for the progression of tumor angiogenesis .
More recently, Scutellaria baicalensis was used as a component of PCSPES, an herbal mixture that showed efficacy in laboratory trials for prostate cancer, small-cell lung cancer and acute myeloid leukemia [29–34]. Despite these promising results in human trials, this herbal mixture was removed from the market due to concerns about contamination . Subsequent work has shown that flavonoids from S. baicalensis were likely to have been at least one of the active ingredients in this herbal mixture , and S. baicalensis extract and its constituents have been shown to cause reduced expression of the androgen receptor and androgen regulated genes in prostate carcinoma . Recent studies have also shown that the flavonoid-rich extract from the roots of S. baicalensis exhibit antiproliferative effects upon prostate, squamous, colon, breast, lung, and liver carcinomas, as well as various leukemia cell lines [16, 21, 36, 37]; however, there have been no studies conducted in brain tumors despite suggestions that components of this extract can have effects on microglia in the brain . We, therefore, tested an extract from the root of S. baicalensis to determine if it had antiproliferative effects on cells from human malignant brain tumors alone or in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine), an alkylating agent commonly used in the treatment of human brain tumors.