Sunday, 23 March 2014

Ovarian Cancer in Vitamin K Points of View

 Kyle J. Norton
Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovaries,  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.
Vitamin K(K1, phylloquinone; K2, menaquinones), is a fat soluble vitamin, found abundantly in leafy green vegetables, broccoli, and Brussels sprouts, etc. It is best known for promotion of coagulation and bone health.

Researchers at the Showa University indicated that vitamin K may process the anti wide array of human cancer cell lines properties through differentiation and apoptosis(1). DR. Shibayama-Imazu, the leader of the research team said that these inductions may be through interruption of the morphological changes and DNA fragmentation via the loss of mitochondrial membrane potential (DeltaPsim caused by superoxide(1).  Vitamin K2 also induced apoptosis of human ovary cancer cells (TYK-nu cells), through the process of production of superoxide, induced oxidative stress in mitochondria might damage mitochondrial membranes(2). In PA-1 ovarian cancer cells, vitamin exhibited apoptosis through increased in the synthesis of TR3 and the accumulation of TR3 in mitochondria and in nuclei via a JNK signaling pathway(3). Against human ovarian carcinoma cell line (MDAH 2774), the composition of VC (ascorbic acid) and VK3 (menadione), inhibited cell proliferation through DNA degradation(4) and exposure to the composition also expressed the anti proliferation of cell death through autoschizis (43%), apoptosis (3%), and oncosis (1.9%)(5). In the comparison of the effect of vitamin K(2) (menaquinone 4) and  geranylgeraniol (GGO)inhuman cancer cell line, showed that GGO inhibited the growth of all eight cell lines derived from solid tumors, while vitamin K(2) selectively inhibited the proliferation and induced apoptosis in both ovarian cell lines(6). Study of the cytotoxic effect and mechanism of action of vitamins C (VC) and K3 (VK3) on ovarian carcinoma, indicated a positive effects of the composition in induced cell death  (displayed characteristics of both apoptosis and necrosis), through cycle arrest and degradation of chromosomal DNA(7).

Taking all together, vitamin VK2 and VK3 are found effectively in reduced risk and treatment of ovarian cancer through activation of cell death mechanism, via activation of RSO, cell cycle arrest,  and inhibition of cell proliferation via degradation of DNA. Large sample and multi centers studies to validate this effectiveness are necessary. Overdoses can induce symptoms of Skin rash,  Diarrhea, Nausea, Vomiting, Anemia, etc. Please make sure you follow the guideline of the Institute of Medicine of the National Academies

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(1) Vitamin K2-mediated apoptosis in cancer cells: role of mitochondrial transmembrane potential. by Shibayama-Imazu T1, Aiuchi T, Nakaya K. (PubMed)
(2) Production of superoxide and dissipation of mitochondrial transmembrane potential by vitamin K2 trigger apoptosis in human ovarian cancer TYK-nu cells by Shibayama-Imazu T1, Sonoda I, Sakairi S, Aiuchi T, Ann WW, Nakajo S, Itabe H, Nakaya K.(PubMed)
(3) Induction of apoptosis in PA-1 ovarian cancer cells by vitamin K2 is associated with an increase in the level of TR3/Nur77 and its accumulation in mitochondria and nuclei by Sibayama-Imazu T1, Fujisawa Y, Masuda Y, Aiuchi T, Nakajo S, Itabe H, Nakaya K.(PubMed)
(4) Autoschizis: a new form of cell death for human ovarian carcinoma cells following ascorbate:menadione treatment. Nuclear and DNA degradation by Gilloteaux J1, Jamison JM, Lorimer HE, Jarjoura D, Taper HS, Calderon PB, Neal DR, Summers JL.(PubMed)
(5) Microscopic aspects of autoschizic cell death in human ovarian carcinoma (2774) cells following vitamin C, vitamin K3 or vitamin C:K3 treatment by Gilloteaux J1, Jamison JM, Arnold D, Taper HS, Von Gruenigen VE, Summers JL.(PubMed)
(6) Vitamin K(2) selectively induced apoptosis in ovarian TYK-nu and pancreatic MIA PaCa-2 cells out of eight solid tumor cell lines through a mechanism different from geranylgeraniol by Shibayama-Imazu T1, Sakairi S, Watanabe A, Aiuchi T, Nakajo S, Nakaya K.(PubMed)
(7) The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma by von Gruenigen VE1, Jamison JM, Gilloteaux J, Lorimer HE, Summers M, Pollard RR, Gwin CA, Summers JL.(PubMed)

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