Natural Cancer Therapy and Prevention Targeted on Cancer Cells and Cancer Stem Cells Based on the Cytochrome P45O Enzyme CYP1B1: A Commentary

摘要

The importance of the P450 enzyme CYP1B1 in both cancer therapy and prevention are reviewed and evidence is discussed, which provides strong biological plausibility for the therapeutic merits of this approach. The significant resistance to chemotherapy among common cancers, and the realization that in many cases chemotherapy leaves behind drug-resistant cancer cells that eventually cause recurrence and metastatic disease, has recently prompted the search for natural compounds that would circumvent this problem. There is also the important question of therapies that will kill cancer stem cells (CSCs) because they appear, in many cases, to be resistant to conventional therapy. The repeated observation that resveratrol has the ability kill CSCs in a variety of cancers suggests that this natural product may act through a mechanism that is cancer-type independent. There are a few other natural products that have this property and all act through a well-understood mechanism involving CYP1B1, which is known to be overexpressed at the protein level in ordinary cancer cells but not in noncancer cells. These natural products toxic to ordinary cancer cells serve as substrates for this enzyme and the metabolites cause apoptosis or cell cycle arrest. This small group includes resveratrol. The observation that resveratrol also has this same action on CSCs independent of cancer type suggests the hypothesis that these cells also overexpress CYP1B1 and offer the same target as ordinary cancer cells. A number of case histories are reviewed that involve a variety of cancers from different sites and grades or stages treated with a proprietary mixture of CYP1B1 substrates extracted from fruit. They illustrate therapeutic effectiveness with even late-stage cancers put into durable remission. This implies combined ordinary cancer cell and CSC toxicity. In addition, a recent proposed mechanism for CYP1B1 overexpression only in cancer cells are described. Recently developed blood tests for CYP1B1, its cancer active substrates, and the resultant metabolites are reviewed as they add significantly to the biological plausibility of the CYP1B1 mechanism. Thus, a targeted therapy many researchers are actively seeking already exists with evidence of human efficacy and compelling biological plausibility.