Novel Role of Vitamin K2: A Potent Inducer of Differentiation of Various Human Myeloid Leukemia Cell Lines

Sakai, Itaru; Hashimoto, Sachiko; Yoda, Madoka; Hida, Toshie H; Ohsawa, Shigemitsu; Nakajo, Shigeo; Nakaya, K.

doi:10.1006/bbrc.1994.2807

Cited by 51 publications

(47 citation statements)

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“…Vitamin K 2 inhibits the growth of various neoplastic cells, including hepatoma cells, by causing cell-cycle arrest and apoptosis through different proposed mechanisms [116][117][118][119][120][121][122].…”

Section: Vitamin Kmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

et al. 2010

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Introduction The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. Methods The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. 123Hepatol Int (2010) 4: 439-474 DOI 10.1007/s12072-010-9165-7 Results Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.

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Section: Vitamin Kmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

et al. 2010

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“…Others have reported that VK2 also induces differentiation of acute myeloid leukemia cell lines such as HL-60 and U937. 9 Recently, we observed that VK2 treatment induced monocytic differentiation in HL-60-bcl-2 cells, which enforced overexpression of BCL-2 by gene transfection, whereas VK2 induced apoptosis in HL-60-neo cells. 10 It is noteworthy that although HL-60-bcl-2 became almost completely resistant to apoptosis induction by VK2, monocytic differentiation via G0/G1 arrest was still observed.…”

Section: Introductionmentioning

confidence: 99%

Combination of 22-oxa-1,25-dihydroxyvitamin D3, a vitamin D3 derivative, with vitamin K2 (VK2) synergistically enhances cell differentiation but suppresses VK2-inducing apoptosis in HL-60 cells

et al. 2002

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“…It has been shown that vitamins K1, K2 and K3 could inhibit the growth of various rodent-and human-derived neoplastic cell lines in vitro, such as oral epidermal cancer, nasopharyngeal cancer, breast cancer, leukemia and hepatocellular carcinoma (HCC) cell lines (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). In marked contrast to numerous reports demonstrating in vitro antitumor effects of vitamin K, there are few reports demonstrating in vivo antitumor effects of vitamin K. Furthermore, it has not been examined so far whether vitamin K induces antitumor effects on CRC.…”

Section: Introductionmentioning

confidence: 99%

Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells

Ogawa¹,

Nakai²,

Deguchi³

et al. 2007

Int J Oncol

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Abstract. Although a number of studies have shown that vitamin K possesses antitumor activities on various neoplastic cell lines, there are few reports demonstrating in vivo antitumor effects of vitamin K, and the antitumor effect on colorectal cancer (CRC) remains to be examined. Therefore, antitumor effects of vitamin K on CRC were examined both in vitro and in vivo. Vitamins K2, K3 and K5 suppressed the proliferation of colon 26 cells in a dose-dependent manner, while vitamin K1 did not. On flow cytometry, induction of apoptosis by vitamins K2, K3 and K5 was suggested by population in sub-G1 phase of the cell cycle. Hoechst 33342 staining and a twocolor flow cytometric assay using fluorescein isothiocyanateconjugated annexin V and propidium iodide confirmed that vitamins K2, K3 and K5 induced apoptotic death of colon 26 cells. Enzymatic activity of caspase-3 in colon 26 cells was significantly up-regulated by vitamins K2, K3 and K5. The pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Aspfluoromethyl ketone, substantially prevented vitamin Kmediated apoptosis. In vivo study using syngeneic mice with subcutaneously established colon 26 tumors demonstrated that intravenous administration of vitamins K2, K3 and K5 significantly suppressed the tumor growth. The number of apoptotic tumor cells was significantly larger in the vitamin K-treated groups than in the control group. These results suggest that vitamins K2, K3 and K5 exerted effective antitumor effects on CRC in vitro and in vivo by inducing caspasedependent apoptotic death of tumor cells, suggesting that these K vitamins may be promising agents for the treatment of patients with CRC. IntroductionWorldwide, colorectal cancer (CRC) ranks third in cancer incidence after lung and breast, and is a major cause of cancer mortality (1). In 2000, there were 943,000 new cases diagnosed and 510,000 deaths worldwide, corresponding figures for Europe were 363,000 cases and 199,000 deaths (2). Although surgery alone is the standard approach in localized malignancy, approximately 50% of early-stage patients present disease relapse (3). Furthermore, approximately 30% of CRC is diagnosed when it is already at an advanced stage. There are also a considerable number of patients who cannot undergo surgery even at an early stage of the disease due to severe complications, such as chronic heart failure, chronic renal failure and chronic obstructive pulmonary diseases. Fluoropyrimidine-based chemotherapy is now considered the standard treatment for patients with inoperable CRC, but approximately 90% of patients do not respond to chemotherapy based on 5-fluorouracil (5-FU)/folinic acid (4). Thus, the development of new treatment modalities is necessary to improve the overall survival rate of patients with CRC.Vitamin K is an essential vitamin that was discovered as a fat-soluble anti-hemorrhagic agent. Vitamin K is also known as an obligatory cofactor in the post-translational γ-carboxylation of glutamic acid residues (5-8). Vitamin K-dependent proteins include prothrombin (fact...

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Novel Role of Vitamin K2: A Potent Inducer of Differentiation of Various Human Myeloid Leukemia Cell Lines

Cited by 51 publications

References 0 publications

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

Combination of 22-oxa-1,25-dihydroxyvitamin D3, a vitamin D3 derivative, with vitamin K2 (VK2) synergistically enhances cell differentiation but suppresses VK2-inducing apoptosis in HL-60 cells

Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells

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