CROSS REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of U.S. Provisional Patent Application No. 60/736,620, filed Nov. 14, 2005; and U.S. Nonprovisional patent application Ser. No. 11/559,324, filed Nov. 13, 2006, the contents of each are herein incorporated by reference in their entirety.
BACKGROUND OF THE INVENTION
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While advances in early detection and adjuvant therapy for breast cancer have had a favorable impact on patient survival in general, patients who develop advanced metastatic breast cancer are generally likely to face a less favorable prognosis. Commonly used hormonal and chemotherapeutic agents can lead to transient regression of tumors and can also palliate symptoms related to cancer. However, these treatments are often accompanied by toxicities and intolerable side effects and eventually become ineffective in controlling advanced stage breast cancer and its symptoms. Improvements in survival are modest, even with newer targeted biological agents. Moreover, in most metastatic cancers resistance to available conventional treatment ultimately develops or excessive side effects are seen with conventional therapies.
It is interesting to note that greater than 60% of all chemotherapeutic agents used in the treatment of breast cancer are derived from natural substances (Newman 2003). A fairly recent example is the development of taxanes from the Pacific yew tree, Taxus brevifolia. Throughout the world, it is estimated that approximately 80% of the world population still relies on botanical medicine as the primary source of therapy. In the West, botanical medicine is considered a popular form of complementary and alternative medicine among patients diagnosed with cancer. However, few clinical trials have been conducted to firmly assess the safety and efficacy of botanical agents for the treatment of breast cancer, despite anecdotal case reports of cures and clinical efficacy in women who have relied solely on botanical medicine for treatment. It has previously been shown that the aqueous extract of Scutellaria Barbata can lead to growth inhibition of breast cancer cell lines in vitro (“Antiproliferative activity of Chinese medicinal herbs on breast cancer cells in vitro,” Anticancer Res., 22(6C):3843-52 (2002)). BZL101, a concentrated aqueous extract of Scutellaria Barbata, was evaluated for antiproliferative activity on five breast cancer cell lines (SK-BR-3, MCF7, MDA-MB-231, BT-474, and MCNeuA). These cell lines represent important prognostic phenotypes of breast cancer expressing a range of estrogen and HER2 receptors. BZL101, tested at a 1:10 dilution (15 μg/ml), demonstrated >50% growth inhibition on four of the five cell lines (Campbell, 2002). BZL101 showed >50% growth inhibition on a panel of lung, prostate and pancreatic cancer cell lines. BZL101 at the same dose did not cause >25% of growth inhibition on normal human mammary cells (HuMEC), demonstrating selectivity to cancer cells (Table 1). More so, BZL101 had a mild mitogenic effect on normal human lymphocytes. In cell cycle analysis, BZL101 caused an S phase burst and G1 arrest. BZL101 also attenuated mitochondrial membrane potential causing caspase-independent high molecular grade (HMG) apoptosis.
There is a need for therapies for treatment of patients having metastatic cancers. There is also a need for therapies with reduced, and more specifically minimal, toxicity for patients having metastatic cancers. In particular, there is a need for novel therapies with relatively low toxicity for the treatment of metastatic solid tumors, such as epithelial tumors, and more particularly breast and ovarian cancers.
These and other needs are met by embodiments of the invention.
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OF THE INVENTION
The foregoing and further needs are met by embodiments of the invention, which provide a pharmaceutical composition for the treatment of cancer. The pharmaceutical composition according to the invention comprises a therapeutically effective amount of an extract of the herb Scutellaria Barbata D. Don. The pharmaceutical composition can also contain one or more optional excipients.
These and other needs are further met by embodiments of the invention, which provide a method of treating a patient suffering from cancer. The method comprises administering to a patient suffering from cancer a therapeutically effective amount of an extract of the herb Scutellaria Barbata D. Don.
Other uses and advantages of the present invention will be apparent to the person skilled in the art after having considered the description, including the drawings and claims, herein.
INCORPORATION BY REFERENCE
All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
BRIEF DESCRIPTION OF THE DRAWINGS
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The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
FIG. 1 shows dose-response curves showing the response of several solid cancer tumor cells to aqueous extract of the herb of this invention.
FIG. 2 shows dose-response curves showing the response of several breast solid cancer tumor cells to aqueous extract of the herb of the invention.
FIG. 3 shows dose-response curves comparing the response of breast solid cancer tumor cells and normal breast epithelium to aqueous extract of the herb of this invention.
FIG. 4 shows gel electrophoresis plate, which demonstrates that nuclear DNA disintegration occurs during apoptosis of solid tumor cancer cells in contact with aqueous extracts of the herb of this invention.
FIG. 5 shows the effect of the herb extract of the invention administered intraperitoneally (IP) on the tumors of mice in a xenograft model.
FIG. 6 shows the effect of the herb extract administered by oral gavages and in interaction with cyclophosphamide administered in low dose in the drinking water on the tumors of mice in a xenograft model.
FIG. 7 shows that the herb extract induces apoptosis without activating caspases.
FIG. 8 shows that the herb extract in cell cycle analysis arrests the cells at the G1 phase.
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OF THE INVENTION
This invention relates to extract of Scutellaria barbata where the extract, when placed in contact with solid tumor cancer cells, inhibits the activity, that is the growth and/or proliferation, of the cells. The herb is selected from the species Scutellaria barbata D. Don of the Labiatae Family. Herba Scutellaria Barbata D. Don (Lamiaceae) of the Labiatae family—Ban Zhi Lian (BZL) is grown mainly in areas southeastern of the Yellow River (Huang Po) in the provinces of Sichuan, Jiangsu, Jiangxi, Fujian, Guangdong, Guangxi and Shaanxi but not exclusively. The plant is harvested in late summer and early autumn after it blooms (May-June). The aerial part is cut from the root. Only the aerial part (leaves and stems) is used for BZL101. The herb is dried in the sun and packed as a whole plant. The herb is received with no separation between leaves and stems.
As is described in the Detailed Description section, below, the herb is substantially more active in inhibiting the activity of different types of cancer cells. It is therefore a presently preferred aspect of this invention that the herbal extract obtained from the species Scutellaria barbata. It is a particularly presently preferred aspect of this invention that the herbal extract is obtained from Scutellaria barbata D. Don.
It is an aspect of this invention that the solid tumor cancer cell, the activity of which is inhibited by the herbal extract of this invention is a SKBR3 cell, a MCF7 cell, a MDA-MB231 cell, a BT474 cell or a MCNeuA cell (breast cancer cells), A549 cell, LLC cell (Lung Cancer cells), Panc1 cells, Panc02 cells (Pancreatic cancer cells), PC-3 cells LNCaP cells (Prostate Cancer cells), OVCAR cells, SKOV3 cells (Ovarian Cancer cells). In some embodiments of the invention, the cell line is in vivo, i.e. a xenograft of the tumor line is present in a mammalian model animal, such as a mouse, rat, dog, cat, sheep, goat or other mammal. Thus, the extract of Scutellaria barbata can be used as a standard for the evaluation of potential anti-cancer drugs.
A further aspect of this invention is a method for treating a solid tumor cancer, comprising administering to a patient a therapeutically effective amount of a composition comprising an extract of Scutellaria barbata. It is a presently preferred aspect of this invention that the pharmaceutical composition used to treat a patient comprises an extract of Scutellaria barbata. It is further a particularly presently preferred aspect of this invention that the extract used to treat a patient is obtained from the herb species Scutellaria barbata D. Don.
The solid tumor cancer being treated is an epithelial cell cancer in another aspect of this invention.
The epithelial cell cancer is breast or ovarian cancer in a still aspect of this invention.
An aspect of this invention is a composition comprising a pharmaceutically acceptable carrier of excipient and an extract Scutellaria barbata.
The pharmaceutical composition comprises aqueous extracts of the above herb species in an aspect of this invention.
The pharmaceutical composition comprises alcohol extracts of the above species in a further aspect of this invention. In a presently preferred embodiment of this invention, the alcohol used to extract the herbs is ethyl alcohol.
The pharmaceutical composition comprises a combination of aqueous and alcohol extracts of the above species of herb in still another aspect of this invention.
Table 1 depicts the herb, from which extracts of this invention are obtained, listed by family, genus, species and tradition Chinese name, of this invention
Barbata D. Don
Ban Zhi Lian
Table 2A shows the degree of inhibition of the activity of several in vitro solid breast cancer tumor cell lines by the extract of this invention.