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Satoshi Inoue - One of the best experts on this subject based on the ideXlab platform.
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Vitamin K2 suppresses proliferation and motility of hepatocellular carcinoma cells by activating steroid and xenobiotic receptor.
Endocrine journal, 2009Co-Authors: Kotaro Azuma, Yasuyoshi Ouchi, Tomohiko Urano, Satoshi InoueAbstract:Vitamin K2, known as a cofactor for gamma-carboxylase, also serves as a ligand of a nuclear receptor, Steroid and Xenobiotic Receptor (SXR). Several clinical trials revealed that Vitamin K2 reduced de novo formation and recurrence of hepatocellular carcinoma (HCC). To examine the role of SXR in HCC as a receptor activated by Vitamin K2, the cells stably overexpressing SXR were established using a HCC cell line, HuH7. Overexpression of SXR resulted in reduced proliferation and motility of the cells. Further suppression of proliferation and motility was observed when SXR overexpressing clones were treated with Vitamin K2. These results suggest that the activation of SXR could contribute to tumor suppressive effects of Vitamin K2 on HCC cells.
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Steroid and xenobiotic receptor mediates a novel Vitamin K2 signaling pathway in osteoblastic cells.
Journal of bone and mineral metabolism, 2008Co-Authors: Kuniko Horie-inoue, Satoshi InoueAbstract:The nuclear receptor steroid and xenobiotic receptor (SXR) is a transcriptional regulator activated by various biological and xenobiotic substances. We have recently shown that SXR is expressed in bone and that this receptor is critical for bone metabolism, particularly in osteoblastic cells. Vitamin K2, one of the critical nutrients in bone metabolism, has been demonstrated that it is a potent SXR agonist and modulates the expression of various bone-related genes in osteoblastic cells. Using microarray analysis, we identified novel SXR target genes that were activated by Vitamin K2 in osteoblastic cells. Among them, a small leucine-rich repeat proteoglycan, tsukushi, has been shown to contribute to collagen accumulation, and the protein may interact with another Vitamin K2-inducible SXR target, matrilin-2, a member of the matrilin family that functions as collagen adaptors. Besides functioning as a xenobiotic biosensor, our findings show that SXR is also a Vitamin K2 target and an important transcriptional factor that regulates bone homeostasis in bone cells.
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steroid and xenobiotic receptor sxr mediates Vitamin K2 activated transcription of extracellular matrix related genes and collagen accumulation in osteoblastic cells
Journal of Biological Chemistry, 2006Co-Authors: Tomoe Ichikawa, Satoshi Inoue, Kuniko Horieinoue, Kazuhiro Ikeda, Bruce BlumbergAbstract:Vitamin K2 is a critical nutrient required for blood coagulation. It also plays a key role in bone homeostasis and is a clinically effective therapeutic agent for osteoporosis. We previously demonstrated that Vitamin K2 is a transcriptional regulator of bone marker genes in osteoblastic cells and that it may potentiate bone formation by activating the steroid and xenobiotic receptor, SXR. To explore the SXR-mediated Vitamin K2 signaling network in bone homeostasis, we identified genes up-regulated by both Vitamin K2 and the prototypical SXR ligand, rifampicin, in osteoblastic cells using oligonucleotide microarray analysis and quantitative reverse transcription-PCR. Fourteen genes were up-regulated by both ligands. Among these, tsukushi, matrilin-2, and CD14 antigen were shown to be primary SXR target genes. Moreover, collagen accumulation in osteoblastic MG63 cells was enhanced by Vitamin K2 treatment. Gain- and loss-of-function analyses showed that the small leucine-rich proteoglycan, tsukushi, contributes to Vitamin K2-mediated enhancement of collagen accumulation. Our results suggest a new function for Vitamin K2 in bone formation as a transcriptional regulator of extracellular matrix-related genes, that are involved in the collagen assembly.
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Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor sxr
Journal of Biological Chemistry, 2003Co-Authors: Michelle M Tabb, Satoshi Inoue, Aixu Sun, Changcheng Zhou, Felix Grun, Jody L Errandi, Kimberly M Romero, Hang Pham, Shyamali Mallick, Min LinAbstract:Vitamin K2 is a critical nutrient required for blood clotting that also plays an important role in bone formation. Vitamin K2 supplementation up-regulates the expression of bone markers, increases bone density in vivo, and is used clinically in the management of osteoporosis. The mechanism of Vitamin K2 action in bone formation was thought to involve its normal role as an essential cofactor for γ-carboxylation of bone matrix proteins. However, there is evidence that suggests Vitamin K2 also has a transcriptional regulatory function. Vitamin K2 bound to and activated the orphan nuclear receptor SXR and induced expression of the SXR target gene, CYP3A4, identifying it as a bona fide SXR ligand. Vitamin K2 treatment of osteosarcoma cells increased mRNA levels for the osteoblast markers bone alkaline phosphatase, osteoprotegerin, osteopontin, and matrix Gla protein. The known SXR activators rifampicin and hyperforin induced this panel of bone markers to an extent similar to Vitamin K2. Vitamin K2 was able to induce bone markers in primary osteocytes isolated from wild-type murine calvaria but not in cells isolated from mice deficient in the SXR ortholog PXR. We infer that Vitamin K2 is a transcriptional regulator of bone-specific genes that acts through SXR to favor the expression of osteoblastic markers. Thus, SXR has a novel role as a mediator of bone homeostasis in addition to its role as a xenobiotic sensor. An important implication of this work is that a subset of SXR activators may function as effective therapeutic agents for the management of osteoporosis.
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Vitamin K2 modulates proliferation and function of osteoblastic cells in vitro.
Biochemical and biophysical research communications, 1992Co-Authors: Yoko Akedo, Masao Kaneki, Takayuki Hosoi, Satoshi Inoue, Akira Ikegami, Yuzo Mizuno, Tetsuro Nakamura, Yasuyoshi Ouchi, Hajime OrimoAbstract:Abstract A human osteosarcoma cell line, HOS TE85 cells, and a mouse osteoblastic cell line, MC3T3-E1 cells, were cultured for 3 days in a medium containing various concentrations of menaquinoe-4 (Vitamin K2). As a result, the proliferation of HOS cells was suppressed by Vitamin K2 in a dose dependent manner up to 56 % of control by 10−7M of Vitamin K2 and that of MC3T3-E1 cells was suppressed to 84 % of control by 10−6M of Vitamin K2. Vitamin K2 increased alkaline phosphatase activity in both kinds of cells. Warfarin counteracted the effect of Vitamin K2 on osteoblastic cell proliferation. Our results show that Vitamin K2 modulates proliferation and function of osteoblastic cells by some mechanisms including γ-carboxylation system.
Anthony Mansour - One of the best experts on this subject based on the ideXlab platform.
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Vitamin K2 status and arterial stiffness among untreated migraine patients a case control study
Headache, 2020Co-Authors: Anthony Mansour, Rechdi Ahdab, Yazan Daaboul, Serge Korjian, Daniel Alexander Morrison, Essa Hariri, Maher Salem, Christelle El Khoury, Naji RiachiAbstract:OBJECTIVE We aimed to examine arterial stiffness and Vitamin K2 status in migraine subjects by comparison to controls. BACKGROUND Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but Vitamin K2 status has never been explored in migraine subjects. DESIGN AND METHODS This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for Vitamin K2 status. A propensity-matched scoring method was used. RESULTS A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9 ± 8.4 years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P < .001), as well as higher dp-ucMGP (454.3 ± 116.7 pmol/L vs 379.8 ± 126.6 pmol/L, 95% CI of mean difference [34.63, 114.31], P < .001). Higher cfPWV was associated with higher dp-ucMGP concentrations only in the migraine with aura (MWA) group. Moreover, migraine subjects had a higher frequency of Vitamin K2 deficiency (dp-ucMGP ≥ 500 pmol/L) compared to controls, but this association was not statistically significant (23/73 [31.5%] vs 16/73 [21.9%], P = .193). CONCLUSIONS Individuals with migraine have worse indices of arterial stiffness as compared with their age- and sex-matched control subjects. This increase in arterial stiffness is associated with an increase in markers of Vitamin K2 deficiency in the MWA group.
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Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case‐Control Study
Headache, 2019Co-Authors: Anthony Mansour, Rechdi Ahdab, Yazan Daaboul, Serge Korjian, Daniel Alexander Morrison, Essa Hariri, Maher Salem, Christelle El Khoury, Naji Riachi, Sola Aoun BahousAbstract:OBJECTIVE We aimed to examine arterial stiffness and Vitamin K2 status in migraine subjects by comparison to controls. BACKGROUND Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but Vitamin K2 status has never been explored in migraine subjects. DESIGN AND METHODS This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for Vitamin K2 status. A propensity-matched scoring method was used. RESULTS A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9 ± 8.4 years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P
Jun Iwamoto - One of the best experts on this subject based on the ideXlab platform.
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Vitamin K2 improves femoral bone strength without altering bone mineral density in gastrectomized rats.
Journal of nutritional science and vitaminology, 2014Co-Authors: Jun Iwamoto, Yoshihiro Sato, Hideo MatsumotoAbstract:Gastrectomy (GX) induces osteopenia in rats. The present study examined the skeletal effects of Vitamin K2 in GX rats. Thirty male Sprague-Dawley rats (12 wk old) were randomized by the stratified weight method into the following three groups of 10 animals each: sham operation (control) group; GX group; and GX+oral Vitamin K2 (menatetrenone, 30 mg/kg, 5 d/wk) group. Treatment was initiated at 1 wk after surgery. After 6 wk of treatment, the bone mineral content (BMC), bone mineral density (BMD), and mechanical strength of the femoral diaphysis and distal metaphysis were determined by peripheral quantitative computed tomography and mechanical strength tests, respectively. GX induced decreases in the BMC, BMD, and ultimate force of the femoral diaphysis and distal metaphysis. Vitamin K2 did not significantly influence the BMC or BMD of the femoral diaphysis or distal metaphysis in GX rats, but attenuated the decrease in the ultimate force and increased the stiffness of the femoral diaphysis. The present study showed that administration of Vitamin K2 to GX rats improved the bone strength of the femoral diaphysis without altering the BMC or BMD, suggesting effects of Vitamin K2 on the cortical bone quality.
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Vitamin K2 prevents hyperglycemia and cancellous osteopenia in rats with streptozotocin-induced type 1 diabetes
Calcified tissue international, 2010Co-Authors: Jun Iwamoto, Tsuyoshi Takeda, Yoshihiro Sato, Hideo Matsumoto, Azusa Seki, James K. YehAbstract:The purpose of the present study was to examine the effect of Vitamin K2 on cancellous and cortical bone mass in rats with streptozotocin (STZ)-induced type 1 diabetes. Twenty-seven male Sprague-Dawley rats aged 12 weeks were randomized by the weight-stratified method into the following three groups: age-matched control group, STZ + vehicle group, and STZ + Vitamin K2 group. STZ (40 + 50 mg/kg) was administered intravenously twice during the initial 1-week period. Vitamin K2 (menatetrenone, 30 mg/kg) was administered orally 5 days a week. After 12 weeks of treatment, the serum glucose concentration and femoral length and weight were measured and histomorphometric analysis was performed on the cancellous and cortical bone of the distal femoral metaphysis and femoral diaphysis, respectively. STZ administration induced hyperglycemia and a decrease in femoral weight. The STZ + vehicle group also showed cancellous osteopenia due to a decrease in the number of osteoblasts/bone surface (N.Ob/BS) and the osteoblast surface (ObS)/BS without any significant changes in bone-resorption parameters, but it did not have a significant decrease in cortical bone mass. Administration of Vitamin K2 to STZ-treated rats prevented the development of hyperglycemia and a decrease in femoral weight. Vitamin K2 also prevented cancellous osteopenia by inhibiting the decrease in N.Ob/BS and ObS/BS without significantly affecting bone-resorption parameters, but it did not significantly increase cortical bone mass. These results suggest that Vitamin K2 has beneficial effects on glucose concentration and cancellous bone mass in rats with STZ-induced type 1 diabetes.
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Synergistic effect of Vitamin K2 and prostaglandin E2 on cancellous bone mass in hypophysectomized young rats.
Calcified tissue international, 2006Co-Authors: Jun Iwamoto, Tsuyoshi Takeda, Y. Sato, James K. YehAbstract:Hypophysectomy (HX) results in cessation of bone growth and cancellous osteopenia in rats. It has been reported that prostaglandin E2 (PGE2) improves cortical and cancellous bone mass in HX rats. The purpose of the present study was to examine whether combined administration of Vitamin K2 and PGE2 would have a more beneficial effect on bone than single administration of either alone in HX rats. Forty-three female Sprague-Dawley rats, 6 weeks of age, were randomized by the stratified weight method into five groups: intact controls, HX, HX + Vitamin K2 (30 mg/kg, p.o., daily), HX + PGE2 (0.83 mg/kg, i.m., 5 days a week), and HX + Vitamin K2 + PGE2. The duration of the experiment was 4 weeks. There was a reduction in cancellous bone volume/total tissue volume (BV/TV) of the proximal tibial metaphysis and a reduction in total tissue area and cortical area (Ct.Ar) of the tibial diaphysis. Vitamin K2 did not affect cancellous BV/TV or Ct.Ar. On the other hand, PGE2 attenuated the loss of cancellous BV/TV in association with higher bone formation rate/bone surface (BFR/BS) and eroded surface (ES)/BS compared with intact controls. PGE2 also increased percent Ct.Ar compared with nontreated HX rats as a result of attenuation of a decrease in periosteal BFR/BS. Vitamin K2 had a synergistic effect with PGE2 on cancellous BV/TV as a result of the suppression of an increase in ES/BS observed by PGE2 treatment. These results suggested that PGE2 had an anabolic action on cancellous and cortical bone and that despite no apparent effect of Vitamin K2 on bone, it had a synergistic effect with PGE2 on cancellous bone mass in young HX rats.
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Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis
Yonsei medical journal, 2006Co-Authors: Jun Iwamoto, Tsuyoshi Takeda, Yoshihiro SatoAbstract:Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of Vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and Vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and Vitamin K2 improved the bone strength of the femoral neck. The use of Vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, Vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, Vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of Vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that Vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, Vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of Vitamin K2 on bone mass and bone metabolism seem to be modest.
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Role of Vitamin K2 in the treatment of postmenopausal osteoporosis.
Current drug safety, 2006Co-Authors: Jun Iwamoto, Tsuyoshi Takeda, Yoshihiro SatoAbstract:Vitamin K2, raloxifene, and bisphosphonates, such as etidronate, alendronate, and risedronate, are widely used in the treatment of postmenopausal osteoporosis in Japan. A meta-analysis study has demonstrated the efficacy of anti-resorptive agents: raloxifene and etidronate have been shown to reduce the incidence of vertebral fractures, and alendronate and risedronate have been shown to reduce the incidence of both vertebral and hip fractures. Furthermore, a report of the World Health Organization (WHO) has provided evidence from a randomized controlled trial suggesting that Vitamin K2, which may stimulate bone formation via gamma-carboxylation of osteocalcin and/or steroid and xenobiotic receptors (SXRs), reduces the incidence of vertebral fractures, despite having only modest effects on the bone mineral density (BMD). Based on the weight of the currently available evidence, it is recommended that alendronate and risedronate, rather than Vitamin K2, should be chosen initially for the treatment of postmenopausal osteoporosis, because these agents have been shown to be the most efficacious for reducing the incidence of both vertebral and hip fractures among the current range of commercially available agents. However, the more potent anti-fracture efficacy of combined treatment with the anti-resorptive and commercially available anabolic agents may need to be established. Some studies have shown that combined treatment with a bisphosphonate and Vitamin K2 may be more effective than treatment with a bisphosphonate alone in preventing vertebral fractures. On the other hand, the results of a preclinical study do suggest the possible efficacy of combined treatment with Vitamin K2 and raloxifene in the prevention of vertebral and hip fractures in postmenopausal women, although no clinical studies have reported on the effects of combined treatment with Vitamin K2 and raloxifene in postmenopausal women with osteoporosis. Vitamin K deficiency, as indicated by high serum levels of undercarboxylated osteocalcin, has been shown to contribute to the occurrence of hip fractures in elderly women. Thus, we propose that the important role of Vitamin K2 used in combination with bisphosphonates or raloxifene should not be underestimated in the prevention of fractures in postmenopausal women with osteoporosis with Vitamin K deficiency.
Naji Riachi - One of the best experts on this subject based on the ideXlab platform.
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Vitamin K2 status and arterial stiffness among untreated migraine patients a case control study
Headache, 2020Co-Authors: Anthony Mansour, Rechdi Ahdab, Yazan Daaboul, Serge Korjian, Daniel Alexander Morrison, Essa Hariri, Maher Salem, Christelle El Khoury, Naji RiachiAbstract:OBJECTIVE We aimed to examine arterial stiffness and Vitamin K2 status in migraine subjects by comparison to controls. BACKGROUND Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but Vitamin K2 status has never been explored in migraine subjects. DESIGN AND METHODS This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for Vitamin K2 status. A propensity-matched scoring method was used. RESULTS A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9 ± 8.4 years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P < .001), as well as higher dp-ucMGP (454.3 ± 116.7 pmol/L vs 379.8 ± 126.6 pmol/L, 95% CI of mean difference [34.63, 114.31], P < .001). Higher cfPWV was associated with higher dp-ucMGP concentrations only in the migraine with aura (MWA) group. Moreover, migraine subjects had a higher frequency of Vitamin K2 deficiency (dp-ucMGP ≥ 500 pmol/L) compared to controls, but this association was not statistically significant (23/73 [31.5%] vs 16/73 [21.9%], P = .193). CONCLUSIONS Individuals with migraine have worse indices of arterial stiffness as compared with their age- and sex-matched control subjects. This increase in arterial stiffness is associated with an increase in markers of Vitamin K2 deficiency in the MWA group.
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Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case‐Control Study
Headache, 2019Co-Authors: Anthony Mansour, Rechdi Ahdab, Yazan Daaboul, Serge Korjian, Daniel Alexander Morrison, Essa Hariri, Maher Salem, Christelle El Khoury, Naji Riachi, Sola Aoun BahousAbstract:OBJECTIVE We aimed to examine arterial stiffness and Vitamin K2 status in migraine subjects by comparison to controls. BACKGROUND Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but Vitamin K2 status has never been explored in migraine subjects. DESIGN AND METHODS This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for Vitamin K2 status. A propensity-matched scoring method was used. RESULTS A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9 ± 8.4 years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P
Ling Hong - One of the best experts on this subject based on the ideXlab platform.
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Vitamin K2 promotes pi3k akt hif 1α mediated glycolysis that leads to ampk dependent autophagic cell death in bladder cancer cells
Scientific Reports, 2020Co-Authors: Fengsen Duan, Huageng Liang, Chunlei Mei, Luhao Yang, Junyan Zheng, Yanzhi Xia, Stacy Hsu, Ling HongAbstract:Vitamin K2 has been shown to exert remarkable anticancer activity. However, the detailed mechanism remains unclear. Here, our study was the first to show that Vitamin K2 significantly promoted the glycolysis in bladder cancer cells by upregulating glucose consumption and lactate production, whereas inhibited TCA cycle by reducing the amounts of Acetyl-CoA. Moreover, suppression of PI3K/AKT and HIF-1α attenuated Vitamin K2-increased glucose consumption and lactate generation, indicating that Vitamin K2 promotes PI3K/AKT and HIF-1α-mediated glycolysis in bladder cancer cells. Importantly, upon glucose limitation, Vitamin K2-upregulated glycolysis markedly induced metabolic stress, along with AMPK activation and mTORC1 pathway suppression, which subsequently triggered AMPK-dependent autophagic cell death. Intriguingly, glucose supplementation profoundly abrogated AMPK activation and rescued bladder cancer cells from Vitamin K2-triggered autophagic cell death. Furthermore, both inhibition of PI3K/AKT/HIF-1α and attenuation of glycolysis significantly blocked Vitamin K2-induced AMPK activation and subsequently prevented autophagic cell death. Collectively, these findings reveal that Vitamin K2 could induce metabolic stress and trigger AMPK-dependent autophagic cell death in bladder cancer cells by PI3K/AKT/HIF-1α-mediated glycolysis promotion.
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Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways.
PloS one, 2016Co-Authors: Fengsen Duan, Rijian Guan, Huageng Liang, Ling HongAbstract:The effects of Vitamin K2 on apoptosis in a variety of cancer cells have been well established in previous studies. However, the apoptotic effect of Vitamin K2 on bladder cancer cells has not been evaluated. The aim of this study is to examine the apoptotic activity of Vitamin K2 in bladder cancer cells and investigate the underlying mechanism. In this study, Vitamin K2 induced apoptosis in bladder cancer cells through mitochondria pathway including loss of mitochondria membrane potential, cytochrome C release and caspase-3 cascade. Furthermore, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK was detected in Vitamin K2-treated cells and both SP600125 (an inhibitor of JNK) and SB203580 (an inhibitor of p38 MAPK) completely abolished the Vitamin K2-induced apoptosis and loss of mitochondria membrane potential. Moreover, the generation of reactive oxygen species (ROS) was detected in bladder cancer cells, upon treatment of Vitamin K2 and the anti-oxidant N-acetyl cysteine (NAC) almost blocked the Vitamin K2-triggered apoptosis, loss of mitochondria membrane potential and activation of JNK and p38 MAPK. Taken together, these findings revealed that Vitamin K2 induces apoptosis in bladder cancer cells via ROS-mediated JNK/p38 MAPK and Mitochondrial pathways.
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Vitamin K2 induces mitochondria related apoptosis in human bladder cancer cells via ros and jnk p38 mapk signal pathways
PLOS ONE, 2016Co-Authors: Fengsen Duan, Rijian Guan, Huageng Liang, Ling HongAbstract:The effects of Vitamin K2 on apoptosis in a variety of cancer cells have been well established in previous studies. However, the apoptotic effect of Vitamin K2 on bladder cancer cells has not been evaluated. The aim of this study is to examine the apoptotic activity of Vitamin K2 in bladder cancer cells and investigate the underlying mechanism. In this study, Vitamin K2 induced apoptosis in bladder cancer cells through mitochondria pathway including loss of mitochondria membrane potential, cytochrome C release and caspase-3 cascade. Furthermore, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK was detected in Vitamin K2-treated cells and both SP600125 (an inhibitor of JNK) and SB203580 (an inhibitor of p38 MAPK) completely abolished the Vitamin K2-induced apoptosis and loss of mitochondria membrane potential. Moreover, the generation of reactive oxygen species (ROS) was detected in bladder cancer cells, upon treatment of Vitamin K2 and the anti-oxidant N-acetyl cysteine (NAC) almost blocked the Vitamin K2-triggered apoptosis, loss of mitochondria membrane potential and activation of JNK and p38 MAPK. Taken together, these findings revealed that Vitamin K2 induces apoptosis in bladder cancer cells via ROS-mediated JNK/p38 MAPK and Mitochondrial pathways.
