Vitamin K2, a Naturally Occurring Menaquinone, Exerts Therapeutic Effects on Both Hormone-Dependent and Hormone-Independent Prostate Cancer Cells

Abstract

In recent years, several studies have shown that vitamin k2 (VK2) has anticancer activity in a variety of cancer cells. The antitumor effects of VK2 in prostate cancer are currently not known. In the present study, we sought to characterize the anticancer potential of VK2 in both androgen-dependent and -independent prostate cancer cells. Our investigations show that VK2 is able to suppress viability of androgen-dependent and androgen-independent prostate cancer cells via caspase-3 and -8 dependent apoptosis. We also show that VK2 treatment reduces androgen receptor expression and PSA secretion in androgen-dependent prostate cancer cells. Our results also implicate VK2 as a potential anti-inflammatory agent, as several inflammatory genes are downregulated in prostate cancer cells following treatment with VK2. Additionally, AKT and NF-kB levels in prostate cancer cells are reduced significantly when treated with VK2. These findings correlated with the results of the Boyden chamber and angiogenesis assay, as VK2 treatment reduced cell migration and angiogenesis potential of prostate cancer cells. Finally, in a nude mice model, VK2 administration resulted in significant inhibition of both androgen-dependent and androgen-independent tumor growth. Overall, our results suggest that VK2 may be a potential therapeutic agent in the treatment of prostate cancer.

Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways

“…Although some studies have revealed vitamin K2 exerted anticancer effect mainly by blocking the cell cycle at the G1 phase and inducing the caspase-3-mediated apoptosis, the detailed mechanism of anticancer effect of vitamin K2 remains unclear[17–19]. In this study, we demonstrated vitamin K2 induced apoptosis in human bladder cancer cells via generation of reactive oxygen species (ROS) which subsequently mediated MAPK and Mitochondrial pathways.…”

Real-time cell analysis of the inhibitory effect of vitamin K2 on adhesion and proliferation of breast cancer cells

“…The anticancer activity of VK 2 has also been demonstrated in in vivo studies of colon and prostate cancer [14,16]. A number of mechanisms underlying the anticancer properties of VK 2 have been suggested including apoptosis and cell cycle arrest [17][18][19].…”

“…In addition to its established function as an antihemorrhagic agent, VK 2 has showed promise as an anticarcinogenic agent in studies involving many cancer cell types including leukemia and cancers of the liver, stomach, lung, ovary, glioblastoma, and prostate [9][10][11][12][13][14][15]. The anticancer activity of VK 2 has also been demonstrated in in vivo studies of colon and prostate cancer [14,16].…”

Elucidation of the glycosylation steps during biosynthesis of antitumor macrolides PM100117 and PM100118 and engineering for novel derivatives

“…Based on our current knowledge on PM100117/18 biosynthesis, no suitable explanation to this observation can be exposed. Moreover, the naphthoquinone chromophore and its derivative compound 7 do not show in vitro cytotoxic activity (Table 1), in spite of the structural and biosynthetic connection of these products to menaquinone, whose antitumor properties have been repeatedly noted [44, 45]. Furthermore, as it was predictable from a previous report [32], removal of large portions from PM100117/18 structure, as displayed in different degrees by compounds 5, 10, 11, 12 and 13, resulted in a remarkable decrease of in vitro cytotoxicity.…”