The anticancer effects of vitamin K

Alternative Medicine Review,  August, 2003  by Davis W. Lamson,  Steven M. Plaza

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[FIGURES 1-3 OMITTED]

Menaquinones (K2) also occur naturally, but are not produced by plants; rather, they are produced by a vast array of bacteria. Menaquinones were originally isolated from putrefied fishmeal as a product of microbial synthesis. (28) Recent studies have discovered menaquinones can actually be produced by animals and probably humans from the conversion of other forms of vitamin K. (29,30) The most common form of vitamin K in animals is menaquinone 4 (MK-4), produced by intestinal bacteria from exogenous naphthoquinones and transformed endogenously in our own cells. (1) Vitamins K1 and K2 differ only in the prosthetic group at position 3 (Figures 1 and 2). Vitamin K1 possesses a phytyl group (partially saturated poly-isoprenoid group) at position 3, while K2 possesses a repeating unsaturated trans-poly-isoprenyl group. The IUPAC-IUB Commission on Biochemical Nomenclature abbreviates phylloquinone (K1) as "K" while menaquinone (K2) is abbreviated as "MK-n." The "n" signifies the number of unsaturated isoprene units that compose the side chain at the 3-position. The side chain of MK-n can vary in length from [C.sub.5] (n=1) to [C.sub.65] (n=13). For example, menaquinone 7 (MK-7) could also be written as K[2.sub.35]. MK-7 has six isoprene units plus the first saturated group beginning at position 3, equaling seven (Figure 2). It is believed that bacteria produce a series of menaquinones with 85 95 percent having an n of 7.8, or 9. (31)

Menadione (K3) is not considered a natural vitamin K, but rather a synthetic analogue that acts as a provitamin. It possesses a much simpler structure, with no aliphatic chain prosthetic group at position 3 (Figure 3). Although menadione is considered a synthetic analogue, Billeter et al found that phylloquinone can be cleaved to form menadione by bacteria in the intestine. (29, 32) After absorption, menadione is thought to become alkylated into biologically active isoprenylated menaquinones. However, K3 cannot exert all the functions of natural vitamin K, which is ascribed to limited transformation into the fat-soluble vitamin forms. (31,33)

Cancer Research on Vitamin K Menadione (Vitamin K3)

The antitumor action of vitamin K has been under investigation since 1947. (34,35) Menadione (150-200 mg/day IV), as a radiosensitizing agent, was discovered to increase survival time (5.42 months with menadione and radiation versus 3.77 months with radiation alone) in inoperable bronchial carcinoma patients. (36) Pretreatment of mice with transplanted mouse liver tumors by oral or intraperitoneal injection of vitamins K3 and C greatly potentiated the action of radiation (20-40 Gy dosages) compared to controls. (37) In rats, menadione was active against adriamycin-resistant leukemia cells. (38) Hepatoma-bearing rats receiving intraperitoneal injections of menadione (10 mg/2mL weekly for four weeks) demonstrated an increased survival rate of 60 days compared to 17 days for controls (five of 16 lived longer than controls). (15) The anticancer activity of menadione has also been demonstrated in a number of in vitro studies using both rodent (10,39-42) and human cancer cell lines. (11,12,43-45) Menadione was effective against multidrug-resistant leukemia cell lines and parental leukemia cell lines. (43)