Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines

Enomoto, Masanobu; Tsuchida, Akihiko; Miyazawa, Kenji; Yokoyama, Tomohisa; Kawakita, Hideaki; Tokita, Hiromi; Naito, Makoto; Itoh, Masahiro; Ohyashiki, Kazuma; Aoki, Tatsuya

doi:10.3892/ijmm.20.6.801

Cited by 25 publications

(30 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cholangiocellular carcinoma cells treated with vitamin K2 doses of 10 to 50 Amol/L evidenced profound accumulation of autophagic vacuoles and cell growth inhibition with limited evidence of apoptosis (199). In contrast, vitamin K2 -treated HL-60 leukemia cells evidenced a stronger apoptotic response associated with blockage of cell growth.…”

Section: Nutrientsmentioning

confidence: 90%

Diet, Autophagy, and Cancer: A Review

Singletary

Milner

2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

146

102

View full text Add to dashboard Cite

A host of dietary factors can influence various cellular processes and thereby potentially influence overall cancer risk and tumor behavior. In many cases, these factors suppress cancer by stimulating programmed cell death. However, death not only can follow the well-characterized type I apoptotic pathway but also can proceed by nonapoptotic modes such as type II (macroautophagy-related) and type III (necrosis) or combinations thereof. In contrast to apoptosis, the induction of macroautophagy may contribute to either the survival or death of cells in response to a stressor. This review highlights current knowledge and gaps in our understanding of the interactions among bioactive food constituents, autophagy, and cancer. Whereas a variety of food components including vitamin D, selenium, curcumin, resveratrol, and genistein have been shown to stimulate autophagy vacuolization, it is often difficult to determine if this is a protumorigenic or antitumorigenic response. Additional studies are needed to examine dose and duration of exposures and tissue specificity in response to bioactive food components in transgenic and knockout models to resolve the physiologic implications of early changes in the autophagy process. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1596 -610)

show abstract

Section: Nutrientsmentioning

confidence: 90%

Diet, Autophagy, and Cancer: A Review

Singletary

Milner

2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

146

102

View full text Add to dashboard Cite

show abstract

“…In addition, when vitamin K was administered to mice with colon 26 implanted subcutaneously, a significant growth inhibition and many apoptotic cells were observed compared with the control group (18). In our previous studies, we observed morphologically typical apoptosis in various types of leukemia cell lines including the HL-60 leukemia cell line, a primary culture system of leukemia cells derived from patients with acute leukemia (6), a small cell lung cancer line A547 (8), and a gastric cancer cell line FU97 (9), but we did not note typical findings of apoptosis in any cell lines of the other solid cancer (9,11). Moreover, the percentage of APO2.7 positive cells, an indicator of apoptosis, also showed a significant increase in gastric cancer cell lines other than FU97; however, the percentage tended to increase in three types of cholangiocellular carcinoma cell lines, which was not a statistically significant difference (9).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, in apoptosis-resistant leukemia cell lines and cholangiocarcinoma cell lines, it was shown that autophagy-mediated cell death, i.e., type II programmed cell death, is one of the mechanisms of MK4 inhibiting cell growth (10,11). Autophagy was originally recognized as a biological phenomenon that is enhanced when cells are in starvation and occurs as an adaptation reaction in order for cells to survive (12,13).…”

Section: Introductionmentioning

confidence: 99%

Growth inhibitory effects of vitamin K2 on colon cancer cell lines via different types of cell death including autophagy and apoptosis

Kawakita

Tsuchida²,

Miyazawa³

et al. 2009

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Vitamin K2 (menaquinone-4: MK4) has been reported to inhibit cell growth and induce apoptosis in various tumor cells. We examined the effects of MK4 using three types of colon cancer cell lines: PMCO1, COLO201, and DLD-1. Exposure to MK4 was at concentrations from 5 to 50 μM, growth inhibitory effects were observed dose-dependently in COLO201 and PMCO1, whereas the growth inhibition observed in DLD-1 was minimal. Comparison of COLO201 and PMCO1 cells exhibiting distinct growth inhibitory effects showed that cell death via apoptosis accompanied by activation of caspase-3 was induced in PMCO1, while apoptosis was not induced in COLO201. On the contrary, immunoblot assay using an anti-LC3B antibody showed autophagy induction by addition of MK4 and incubation in all three types of colon cancer cell lines. Addition of 3-methyladenine (3-MA) attenuated the growth inhibitory effect of MK4 in COLO201, whereas no influence of 3-MA was noted in PCMO1. Electron microscopy images of COLO201 showed that addition of MK4 induced an increased number of cytoplasmic autophagosomes and autolysosomes as well as morphological changes including scantiness of cytoplasm accompanied by loss of cell organelles, nuclear shrinkage, and fragmentation of cytoplasmic membrane in some cells, indicating the induction of cell death via autophagy not accompanied by the formation of apoptotic bodies in COLO201 cells. These results suggested that the response to MK4 and the way of induction of cell death vary in different colon cancer cell lines.

show abstract

“…other studies have indicated that VK 3 induces the caspasedependent apoptosis of tumor cells (5)(6)(7). recently, vitamin K2-induced cell growth inhibition was attributed to the induction of autophagy formation in cholangiocellular carcinoma cells (8). However, the mechanisms underlying VK 3 -mediated tumor cell growth inhibition are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of Beclin 1 inhibits vitamin K3‑induced autophagy, but promotes apoptosis of human hepatoma SMMC-7721 cells

Yang

Han

2010

Mol Med Rep

View full text Add to dashboard Cite

Abstract. The aim of the present study was to investigate the effects of Beclin 1 knockdown on spontaneous and vitamin K 3 (VK 3 )-regulated autophagy, survival and apoptosis in human hepatocarcinoma SMMc-7721 cells, and to explore the potential mechanisms underlying the action of Beclin 1 knockdown in the processes of autophagy and apoptosis. a recombinant plasmid-expressing small interfering rna (sirna) targeting Beclin 1 mrna was constructed and introduced into SMMc-7721 cells. The expression of Beclin 1 was determined by reverse transcription-polymerase chain reaction and Western blotting. Subsequently, the impact of Beclin 1 knockdown on spontaneous and VK 3 -induced autophagy, survival and apoptosis was determined. The expression of cyclin d1, cyclindependent kinase 4 (cdK4), Bcl-2, Bcl-xl and the activation of caspase-3 were examined by Western blotting. Transfection with the plasmid for Beclin 1 sirna expression dramatically down-regulated Beclin 1 expression in SMMc-7721 cells. The knockdown of Beclin 1 expression significantly inhibited spontaneous and VK 3 -induced autophagy, but did not affect spontaneous proliferation and apoptosis in SMMc-7721 cells in vitro. By contrast, the silencing of Beclin 1 expression significantly enhanced the inhibition of survival and proliferation by VK 3 , and promoted VK 3 -induced apoptosis by significantly down-regulating cyclin D1, CDK4, Bcl-2 and Bcl-xl expression and enhancing caspase-3 activation in SMMc-7721 cells in vitro. our data indicate that Beclin 1 is a positive regulator of autophagy, but a negative regulator of VK 3 -induced apoptosis in human hepatoma cells.

show abstract

Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines

Cited by 25 publications

References 27 publications

Diet, Autophagy, and Cancer: A Review

Diet, Autophagy, and Cancer: A Review

Growth inhibitory effects of vitamin K2 on colon cancer cell lines via different types of cell death including autophagy and apoptosis

Knockdown of Beclin 1 inhibits vitamin K3‑induced autophagy, but promotes apoptosis of human hepatoma SMMC-7721 cells

Contact Info

Product

Resources

About