Method of Treating Cancer Using Dithiocarbamate Derivatives

Abstract

Dithiocarbamate, particularly tetraethylthiuram disulfide, and thiocarbamate anions thereof, strongly inhibit the growth of cancer cells of a variety of cell types. Such inhibitory effect is enhanced by heavy metal ions such as copper ions, cytokines and ceruloplasmin. A method is presented for using tetraethylthiuram disulfide to reduce tumor growth, and to potentiate the effect of other anticancer agents.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] The present application is a continuation of U.S. application Ser. No. 10 / 378,206, filed Mar. 3, 2003, which is a divisional of U.S. application Ser. No. 09 / 735,205, filed Dec. 12, 2000, now U.S. Pat. No. 6,548,540, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 679,932, filed Oct. 5, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 392,122, filed Sep. 8, 1999, which claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Appl. Ser. No. 60 / 099,390, filed Sep. 9, 1998, all of which are hereby incorporated by reference herein in their entirety.FIELD OF INVENTION [0002] This invention generally relates to methods of treating cancer, and particularly to methods of treating cancer using dithiocarbamate derivatives. BACKGROUND OF THE INVENTION [0003] Cancer, the uncontrolled growth of malignant cells, is a major health problem of the modern medical era and ranks second only to heart dis...

AI Technical Summary

Benefits of technology

[0017] It has been discovered that dithiocarbamate disulfides and their corresponding thiolate anions alone exhibit potent inhibitory effects on growth of established tumor cells in the absence of antioxidant sulfhydryl groups within their structure. Thiocarbamate disulfides and their corresponding thiolate anions are effective in inhibiting the growth of established melanomas and non-small cell lung cancer cells, which are known to be poorly responsive to currently available neoplastic agents. In addition, it has further been surprisingly discovered that the antiproliferative and antineoplastic effect of dithiocarbamate disulfides and their corresponding thiolate anions on established tumor cells is greatly potentiated by co-treatment of cancer cells with a transitional metal salt in a concentration which by itself does not impair cancer cell growth. The potentiating function of the transition metal is to facilitate formation of the thiolate anion from the dithiocarbamate disulfide. Further the tumor cell growth inhibition effect can be significantly enhanced by the addition of heavy metal ions such as copper, zinc, gold and silver ion, as examples, or by administering the thiocarbamate as a heavy metal ion complex.

[0024] In yet another embodiment of the present invention, a method of reducing hypoxic or ischemic damage to the cardiovascular system of a human is provided using a dithiocarbamate disulfide or corresponding thiolate anion.

[0027] The present invention is effective for treating various types of cancer, including but not limited to melanoma, non-small cell lung cancer, small cell lung cancer, renal cancer, colorectal cancer, breast cancer, pancreatic cancer, gastric cancer, bladder cancer, ovarian cancer, uterine cancer, lymphoma, and prostate cancer. In particular the present invention will be especially effective in treating melanoma, lung cancer, breast cancer and prostate cancer. Thus the use of dithiocarbamate disulfides and thiolate anions in this invention offers a readily available and easily used treatment for cancers in man and other animals.

Problems solved by technology

Cancer, the uncontrolled growth of malignant cells, is a major health problem of the modern medical era and ranks second only to heart disease as a cause of death in the United States.

While some malignancies, such as adenocarcinoma of the breast and lymphomas such as Hodgkin's Disease, respond relatively well to current chemotherapeutic antineoplastic drug regimens, other cancers are poorly responsive to chemotherapy, especially non-small cell lung cancer and pancreatic, prostate and colon cancers.

Even small cell cancer of the lung, initially chemotherapy sensitive, tends to return after remission, with widespread metastatic spread leading to death of the patient.

Also, because almost all currently available antineoplastic agents have significant toxicities, such as bone marrow suppression, renal dysfunction, stomatitis, enteritis and hair loss.

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