Sunday, April 11, 2010

June 2010: Cannabinoids inhibit a group of cancer-causing enzymes. (Hokuriku University; Kanazawa, Japan)

Note: June refers to the publication date

First some background: The human body contains an expansive number of enzymes, proteins which increase the rate of chemical reactions in our bodies. These enzymes typically facilitate the various molecular metabolic processes that are occurring at any given second within our cells, but some of their products and/or byproducts can be harmful, even carcinogenic (cause cancer). Perhaps the largest group of enzymes in our bodies is the cytochrome P450 (CYP) family, which catalyze the monooxidation (addition of one oxygen) of various organic molecules. One of the main functions of this enzyme family is the metabolism of drugs in the liver. However, some subfamilies, such as the CYP1 subfamily (enzymes CYP1A1, CYP1A2, CYP1B1), also induce the formation of carcinogenic compounds from polycyclic aromatic hydrocarbons. Polycyclic aromatic hydrocarbons are common constituents of smoke, especially cigarette smoke, and are known as procarcinogens. The label procarcinogen indicates that the molecule in and of itself will not cause cancer, but can be induced to cause cancer when altered by a metabolic process.

The new information: This experiment tested the effects of three cannabinoids found in marijuana on the catalytic effects of CYP1 enzymes. The three cannabinoids used were delta(9)-tetrahydrocannabinol (THC), cannabidiol, and cannabinol; it was found that all three cannabinoids inhibited all three CYP1 enzymes to some degree, with THC being the least potent inhibitor, cannabidiol inhibiting CYP1A1 most effectively, and cannabinol inhibiting CYP1A2 and CYP1B1 most effectively. Additionally, it was shown that all three cannabinoids were competitive inhibitors, meaning that at higher concentrations/potencies of other substrates for the CYP1 enzymes, the cannabinoids were displaced.

What this means: By illustrating that three of the major cannabinoids found in marijuana can cause potent inhibition of all three enzymes in the CYP1 subfamily, marijuana may prevent certain forms of cancer. Polycyclic aromatic hydrocarbons are common components in environmental pollution, and are usually inhaled, resulting in lung cancer. By inhibiting the enzyme that converts the procarcinogen into the cancer-causing compound, cannabis may be prophylactically used to prevent one of the main causes of lung cancer. Additionally, because CYP1 enzymes are also involved in drug metabolism, cannabis could be use to augment various pharmaceuticals for maximal effectiveness. In order for a drug to be excreted from the body, it generally first passes through at least two phases of metabolism, with cytochrome P450 enzymes representing one of the major components of the first phase. Thus if a drug is known to be metabolized by one of the CYP1 enzymes and cannabis is co-administered, it would take longer for the drug to be broken down in and removed from our bodies. Therefore, cannabis could extend the half-life of various medications, possibly reducing the cost to patients.

Yamaori, S., et al. “Characterization of Major Phytocannabinoids, Cannabidiol and Cannabinol, as Isoform-selective and Potent Inhibitors of Human CYP1 Enzymes.” Biochemical Pharmacology. 79.11(2010): 1691-8.

1 comment:

  1. Thanks for this info, I have been in K2 summit and I found out useful stuff also and some useful guidelines.