Researchers at the Malaghan Institute of Medical Research in Wellington, New Zealand have found that abnormally proliferating human T-cells, rapidly dividing cancer cells such as primary myeloid and lymphoid leukemic blast cells undergo programmed cell death when exposed briefly to the investigational anti-tumor drug phenoxodiol.

These results make phenoxodiol a promising candidate for the treatment of pathologically activated lymphocytes such as those in acute lymphoid leukemia, or diseases driven by T-cell proliferation such as autoimmune diseases and graft-versus-host disease, according to an article published in the Haematologica Journal on June 16, 2009, haematologica/cgi/reprint/94/7/928.

The researchers demonstrated that phenoxodiol inhibited plasma membrane electron transport and cell proliferation and promoted apoptosis of rapidly proliferating human T-cells, induced to undergo rapid proliferation by exposure to cells from an incompatible donor, but at the same time it did not affect normal resting T-cells.

"These findings indicate that phenoxodiol may have utility against autoimmune diseases, such as rheumatoid arthritis and psoriasis, as well as having potential in management of graft rejection in transplantation patients," said Prof. Alan Husband, Group Director of Research, Marshall Edwards, Inc. "We're appreciative of Dr. Patries Herst and colleagues for undertaking this important research."

About phenoxodiol

Phenoxodiol is being developed by the U.S. oncology company Marshall Edwards, Inc. (NASDAQ: MSHL) as a chemosensitizing agent in combination with platinum drugs for late stage, chemoresistant ovarian cancer and as a monotherapy for prostate and cervical cancers. It has a unique mechanism of action, binding to cancer cells via a surface oxidase, disrupting membrane electron transport and causing major downstream disturbances in expression of proteins necessary for cancer cell survival and responsible for the development of drug resistance.

In cancer cells, phenoxodiol appears to inhibit selectively the pro-survival regulator known as S-1-P (sphingosine-1-phosphate) that is overexpressed in cancer cells. In response to phenoxodiol, the S-1-P content in cancer cells is decreased, rendering those cells more sensitive to chemotherapy. Indeed, in laboratory studies, it has been demonstrated that cancer cells pre-treated with phenoxodiol were killed with lower doses of chemotherapy drugs.

Importantly, phenoxodiol has been shown not to affect adversely normal cells in animal and laboratory testing. Phenoxodiol is being investigated as a therapy for late-stage, chemoresistant ovarian, prostate and cervical cancers. Phenoxodiol has received Fast Track status from the FDA to facilitate its development as a therapy for recurrent ovarian and prostate cancers. Phenoxodiol is an investigational drug and, as such, is not commercially available. Under U.S. law, a new drug cannot be marketed until it has been investigated in clinical trials and approved by FDA as being safe and effective for the intended use.

Phenoxodiol is the first of a family of compounds in the Marshall Edwards, Inc. drug pipeline of flavonoid derivatives.

Source
Marshall Edwards, Inc.