Abnormal Methylation Enzymes: A Selective Molecular Target for Differentiation Therapy of Cancer

Abstract

A crucial difference between cancer cells and normal cells is the inability of cancer cells to undergo terminal differentiation. Alteration of methylation enzymes plays a pivotal role in the blockade of terminal differentiation of cancer cells. Elimination of abnormal methylation enzymes is, therefore, a logical approach of cancer therapy. Methylation enzymes play a central role in the regulation of cell replication, differentiation, and apoptosis. When these enzymes are activated, cells enter cell cycle replicating; and when these enzymes become inactive, replicating cells are then diverted into terminal differentiation or apoptosis. The activity of these enzymes in normal stem cells is strictly under the regulation of an exogenous growth factor. Cancer cells, on the other hand, produce a cancer specific endogenous protein factor to lock these enzymes in the active state. Thus, cancer cells keep on dividing. This cancer specific protein factor is an attractive molecular target for cancer therapy, which can be selectively antagonized by CDA-Ⅱ*. CDA-Ⅱ is a preparation derived from fresh human urine. Once abnormal methylation enzymes are corrected by CDA-Ⅱ to become normal enzymes, cancer cells are then induced to undergo terminal differentiation or apoptosis. The action of CDA-Ⅱ is selective on cancer cells, thus the therapy is free of adverse side effects. Better yet, many abnormal behaviors characteristic of cancer cells disappear naturally as a consequence of differentiation induced by CDA-Ⅱ, which include abnormal expression of oncogenes, silencing of suppressor genes, drug resistance, metastasis, telomerase, and tumor markers. CDA-Ⅱ has been approved by the State Drug Administration of China to undergo clinical trial, which is now in the final stage of phase Ⅲ. So far the clinical studies are encouraging. The best clinical result in the application of CDA-Ⅱ was, however, demonstrated by Sano of Japan, who has initiated a very effective protocol by combination therapy with vitamin C, restriction of protein intake, and other nontoxic remedies.