Abstract
Vitamin K1 has been demonstrated as having anticancer potentiality mainly in liver cancer cells. Beyond the reported mechanisms of cancer inhibition (cell cycle arrest and induction of apoptosis), a possible control by vitamin K1 on molecules affecting cell growth could be hypothesized. In the literature, few (if any) data are available on its antitumor effects on colon cancer cells. Therefore, the aims of the study were to investigate in three differently graded human colon cancer cell lines (Caco-2, HT-29, and SW480) the effects of increasing concentrations of vitamin K1 (from 10 μM to 200 μM) administered up to 72 h on (1) cell proliferation, (2) apoptosis with the possible involvement of the MAPK pathway, and (3) polyamine biosynthesis. Vitamin K1 treatment caused a significant antiproliferative effect and induced apoptosis in all the cell lines, with the involvement of the MAPK pathway. A concomitant and significant decrease in the polyamine biosynthesis occurred. This is the first study demonstrating a significant polyamine decrease in addition to the antiproliferative and proapoptotic effects following vitamin K1 administration to colon cancer cell lines. Therapeutically, combinations of vitamin K1 with polyamine inhibitors and/or analogues may represent a suitable option for chemoprevention and/or treatment in future strategies for colorectal cancer management.
Highlights
Colorectal cancer (CRC) is a major health problem in industrialized countries [1], but the treatment is still far from being satisfying since approximately 90% of patients do not respond to chemotherapy protocols [2].the development of new treatment modalities is necessary to improve the overall survival rate of patients with CRC.In the last years, an emerging role has been attributed to micronutrients, such as vitamin K (VK)
No data are available about the use of nutritional components such as VK1 for targeting the polyamine pathway in the treatment of CRC. Starting from these bases, the aims of the present study were to investigate in three human colon cancer cells the effects of increasing concentrations of VK1 on (1) the cell proliferation, (2) the apoptotic processes with the possible involvement of the mitogen-activated protein kinase (MAPK) pathway, and (3) the polyamine biosynthesis
The significance of investigations performed in vitro related to the in vivo situations has to be taken with caution due to the presence of several differences; besides, cell sensitivity is only one factor and is not necessarily the most important in determining specificity of VK1 action
Summary
The development of new treatment modalities is necessary to improve the overall survival rate of patients with CRC. An emerging role has been attributed to micronutrients, such as vitamin K (VK). VK is an essential vitamin that was discovered as a fat-soluble antihemorrhagic agent. VK is a family of structurally similar 2-methyl1,4-naphthoquinones, including phylloquinone (VK1), menaquinone (VK2), and menadione (VK3). All members of the VK family possess an identical naphthoquinone skeleton with various side chains that distinguish them. VK2 occurs naturally but is not made by plants being produced by a wide array of bacteria in the intestine. VK3 is not considered a natural VK, but rather a synthetic analogue acting as a provitamin with a much simpler structure and no aliphatic chain prosthetic group at position 3 [3]
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