Vitamin K1 Exerts Antiproliferative Effects and Induces Apoptosis in Three Differently Graded Human Colon Cancer Cell Lines

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.

Antiproliferative effects on colon adenocarcinoma cells induced by co-administration of vitamin K1 and Lactobacillus rhamnosus GG

“…In the present study, before co-administering VK1 and L.GG, their effects on colon cancer cells were checked separately. As already reported (10), the highest VK1 concentrations (100 and 200 µM) administered up to 72 h had a significant antiproliferative and proapoptotic effect in all the tested cells. On the contrary, VK1 administration induced the cell cycle arrest only in two cancer cell lines (Caco-2 and SW480) and required a prolonged time of treatment (72 h).…”

“…VK, an essential nutrient associated with the clotting cascade, has also been demonstrated to have anticancer properties in a variety of cancer cell lines including colon cancer cells (7,(9)(10)(11)37). Many hypotheses have been formulated to explain its ability to inhibit the cell proliferation, including an active induction of the cell cycle arrest, the effects on differentiation and apoptosis with the involvement of the MAPK pathway (7,8) and the control on a class of molecules affecting cell growth such as polyamines (10,11).…”

“…In addition to the above proposed VK1 mechanisms of cancer inhibition, studies by our group demonstrated the ability of VK1 to affect the biosynthesis of cellular polyamines (spermidine, spermine and putrescine), polycations essential for growth and DNA synthesis (10,11) that have also been suggested as putative markers for neoplastic proliferation (12).…”

Suppression of colitis‐associated carcinogenesis through modulation of IL‐6/STAT3 pathway by balsalazide and VSL#3

“…34 ERK is usually known to prevent apoptosis, but several reports have proposed a different meaning of p-ERK. 41 The previous studies showed the pro-apoptotic role of ERK pathway. The sustained increase of ERK activity induced growth arrest and the suppression of p-ERK-inhibited apoptosis.…”

“…A key study regarding the IL‐6/STAT3 pathway showed that IL‐6 −/− mice developed fewer and smaller tumors and revealed downregulation of p‐STAT3 and BCL‐X L . ERK is usually known to prevent apoptosis, but several reports have proposed a different meaning of p‐ERK . The previous studies showed the pro‐apoptotic role of ERK pathway.…”