AIM: To investigate the anti-neoplastic effects of MK615, an extract from the Japanese apricot (Prunus mume), against colon cancer cells. METHODS: Three colon cancer cell lines, SW480, COLO, and WiDr, were cultured wi...AIM: To investigate the anti-neoplastic effects of MK615, an extract from the Japanese apricot (Prunus mume), against colon cancer cells. METHODS: Three colon cancer cell lines, SW480, COLO, and WiDr, were cultured with MK615. Growth inhibition was evaluated by cell proliferation assay and killing activity was determined by lactate dehydrogenase assay. Induction of apoptosis was evaluated by annexin Ⅴ flow cytometry. Morphological changes were studied by light and electron microscopy, and immunofluorescence staining with Atg8. RESULTS: MK615 inhibited growth and lysed SW480, COLO and WiDr cells in a dose-dependent manner. Annexin Ⅴ flow cytometry showed that MK615 induced apoptosis after 6 h incubation, at which point the occurrence of apoptotic cells was 68.0%, 65.7% and 64.7% for SW480, COLO, and WiDr cells, respectively. Light and electron microscopy, and immunofluorescence staining with Atg8 revealed that MK615 induced massive cytoplasmic vacuoles (autophagosomes) in all three cell lines. CONCLUSION: MK615 has an anti-neoplastic effect against colon cancer cells. The effect may be exerted by induction of apoptosis and autophagy.展开更多
MK615, a compound extracted from the Japanese apricot "Prunus mume " has been reported to have in vitro anti-tumor activities against several cancer cell lines,including hepatocellular carcinoma(HCC). Howeve...MK615, a compound extracted from the Japanese apricot "Prunus mume " has been reported to have in vitro anti-tumor activities against several cancer cell lines,including hepatocellular carcinoma(HCC). However, the clinical effects and feasibility of administering MK615for patients with HCC were unknown. We experienced a case with advanced HCC for which MK615 was effective against both lymph node and pulmonary metastases. A 60-year-old female underwent surgical resection of a 9 cm HCC in the right lobe. The pathological diagnosis was moderately differentiated HCC with vascular invasion. The HCC recurred in the liver 8 mo after the surgery. Radiofrequency ablation and transarterial infusion chemotherapy were performed, but the recurrence was not controlled. One year after the intrahepatic recurrence, pulmonary and lymph metastasis appeared.Sorafenib was administered, but was not effective.Then, MK615 was administered as a final alternative therapy after informed consent was obtained from the patient. Three months later, her alpha-fetoprotein level decrease and both the lymph node and pulmonary metastases decreased in size. The patient has survived for more than 17 mo after the MK615 administration, and was in good condition. Although further investigations are necessary to clarify its safety and efficacy in humans, MK615 may be useful for the treatment of HCC,without serious adverse effects.展开更多
AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract ...AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract from Japanese apricot,against AGEs were also evaluated.METHODS:Two HCC cell lines,HuH7 and HepG2,were used.Expression of RAGE was investigated by poly-merase chain reaction,Western blotting,and flow cytemetry(FACS).The effect of MK615 on RAGE expression was also evaluated by FACS.The proliferative effects of a control(unglycated bovine serum albumin),glucosederived AGEs(Glc-AGE),and glyceraldehyde-derived AGEs(Glycer-AGE),and the anti-proliferative effect of MK615 against AGEs,were evaluated using MTT assays.RESULTS:Expression of RAGE was confirmed at both the mRNA and protein levels in both HuH7 and HepG2.FACS revealed that the level of RAGE expression was higher in HuH7 than in HepG2.Treatment with 0.1 μg/mL MK615 decreased the expression level of RAGE from 24.3% to 3.7% in HuH7 and from 6.2% to 4.8% in HepG2.The growth indices for the control,Glc-AGE,and Glycer-AGE were 1.06 ± 0.08,0.99 ± 0.04,and 1.38 ± 0.05,respectively,in HuH7(P = 0.037),and were 1.03 ± 0.04,1.04 ± 0.03,and 1.07 ± 0.05,respectively,in HepG2(P > 0.05).When the cells were cultured simultaneously with Glycer-AGE and MK615,MK615 abrogated the proliferative effect of Glycer-AGE in HuH7.CONCLUSION:Only Glycer-AGE has a proliferative effect on HuH7,which expresses a higher level of RAGE.MK615 suppresses the proliferative effect of GlycerAGE on HuH7 by decreasing the expression of RAGE.展开更多
AIM： To investigate the hepatoprotective effect of MK615, a Japanese apricot extract, in an animal model, and its clinical therapeutic effect. METHODS： Wistar rats were administered physiologi- cal saline （4 mL/kg...AIM： To investigate the hepatoprotective effect of MK615, a Japanese apricot extract, in an animal model, and its clinical therapeutic effect. METHODS： Wistar rats were administered physiologi- cal saline （4 mL/kg） or MK615 solution （4 mL/kg） for 7 d. On the sixth d, acute hepatic injury was induced by administering a single intraperitoneal injection （ip） of D-galactosamine hydrochloride （D-GaIN） （600 mg/kg）. Plasma levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined, and liver tissues were used for histopathological analy- sis. Fifty-eight patients with liver disorders [hepatitis C （n = 40）, non-alcoholic fatty liver disease （n = 15）, and autoimmune liver disease （n = 3）] were orally admin- istered commercially available Misatol ME-containing MK615 （13 g/d） daily for 12 wk. Blood and urine were sampled immediately before and 6 wk, 12 wk, and 16 wk after the start of intake to measure various bio- chemical parameters. The percentage change in ALT and AST levels after 12 wk from the pre-intake baseline served as a primary endpoint. RESULTS： D-GaIN effectively induced acute hepatic injury in the rats. At 48 h after the ip injection of D-GaIN, the plasma levels of ALT （475.6 ：t： 191.5 IU/L vs 225.3 ＋ 194.2 IU/L, P 〈 0.05） and AST （1253.9：1：223.4 IU/L vs 621.9 ＋ 478.2 IU/L, P 〈 0.05） in the MK615 group were significantly lower than the control group. Scattered single cell necrosis, loss of hepatocytes, and extensive inflammatory cell infiltration were observed in hepatic tissue samples collected from the control group. However, these findings were less pronounced in the group receiving MK615. At the end of the clinical study, serum ALT and AST levels were significantly de- creased compared with pre-intake baseline levels from 103.5 ：l： 58.8 IU/L to 71.8 ＋ 39.3 IU/L （P 〈 0.05） and from 93.5 ：E 55.6 IU/L to 65.5 ＋ 34.8 IU/L （P 〈 0.05）, respectively. A reduction of 〉~ 30% from the pre-study baseline ALT level was observed in 26 （45%） of the 58 patients, while 25 （43%） patients exhibited similar AST level reductions. The chronic hepatitis C group exhibit- ed significant ALT and AST level reductions from 93.4：1： 51.1 IU/L to 64.6 ＋ 35.1 IU/L （P 〈 0.05） and from 94.2 ＋ 55.5 IU/L to 67.2：1：35.6 IU/L （P 〈 0.05）, respective- ly. A reduction of 〉~ 30% from the pre-study baseline ALT level was observed in 20 （50%） of the 40 patients.ALT levels in both the combined ursodeoxycholic acid （UDCA） treatment and the UDCA uncombined groups were significantly lower after Misatol ME administration. MK615 protected hepatocytes from D-GaiN-induced cytotoxicity in rats. Misatol ME decreased elevated ALT and AST levels in patients with liver disorders. CONCLUSION： These results suggest that MK615 and Misatol ME are promising hepatoprotective agents for patients with liver disorders.展开更多
文摘AIM: To investigate the anti-neoplastic effects of MK615, an extract from the Japanese apricot (Prunus mume), against colon cancer cells. METHODS: Three colon cancer cell lines, SW480, COLO, and WiDr, were cultured with MK615. Growth inhibition was evaluated by cell proliferation assay and killing activity was determined by lactate dehydrogenase assay. Induction of apoptosis was evaluated by annexin Ⅴ flow cytometry. Morphological changes were studied by light and electron microscopy, and immunofluorescence staining with Atg8. RESULTS: MK615 inhibited growth and lysed SW480, COLO and WiDr cells in a dose-dependent manner. Annexin Ⅴ flow cytometry showed that MK615 induced apoptosis after 6 h incubation, at which point the occurrence of apoptotic cells was 68.0%, 65.7% and 64.7% for SW480, COLO, and WiDr cells, respectively. Light and electron microscopy, and immunofluorescence staining with Atg8 revealed that MK615 induced massive cytoplasmic vacuoles (autophagosomes) in all three cell lines. CONCLUSION: MK615 has an anti-neoplastic effect against colon cancer cells. The effect may be exerted by induction of apoptosis and autophagy.
文摘MK615, a compound extracted from the Japanese apricot "Prunus mume " has been reported to have in vitro anti-tumor activities against several cancer cell lines,including hepatocellular carcinoma(HCC). However, the clinical effects and feasibility of administering MK615for patients with HCC were unknown. We experienced a case with advanced HCC for which MK615 was effective against both lymph node and pulmonary metastases. A 60-year-old female underwent surgical resection of a 9 cm HCC in the right lobe. The pathological diagnosis was moderately differentiated HCC with vascular invasion. The HCC recurred in the liver 8 mo after the surgery. Radiofrequency ablation and transarterial infusion chemotherapy were performed, but the recurrence was not controlled. One year after the intrahepatic recurrence, pulmonary and lymph metastasis appeared.Sorafenib was administered, but was not effective.Then, MK615 was administered as a final alternative therapy after informed consent was obtained from the patient. Three months later, her alpha-fetoprotein level decrease and both the lymph node and pulmonary metastases decreased in size. The patient has survived for more than 17 mo after the MK615 administration, and was in good condition. Although further investigations are necessary to clarify its safety and efficacy in humans, MK615 may be useful for the treatment of HCC,without serious adverse effects.
基金Supported by A Research Grant from the Biomarker Society
文摘AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract from Japanese apricot,against AGEs were also evaluated.METHODS:Two HCC cell lines,HuH7 and HepG2,were used.Expression of RAGE was investigated by poly-merase chain reaction,Western blotting,and flow cytemetry(FACS).The effect of MK615 on RAGE expression was also evaluated by FACS.The proliferative effects of a control(unglycated bovine serum albumin),glucosederived AGEs(Glc-AGE),and glyceraldehyde-derived AGEs(Glycer-AGE),and the anti-proliferative effect of MK615 against AGEs,were evaluated using MTT assays.RESULTS:Expression of RAGE was confirmed at both the mRNA and protein levels in both HuH7 and HepG2.FACS revealed that the level of RAGE expression was higher in HuH7 than in HepG2.Treatment with 0.1 μg/mL MK615 decreased the expression level of RAGE from 24.3% to 3.7% in HuH7 and from 6.2% to 4.8% in HepG2.The growth indices for the control,Glc-AGE,and Glycer-AGE were 1.06 ± 0.08,0.99 ± 0.04,and 1.38 ± 0.05,respectively,in HuH7(P = 0.037),and were 1.03 ± 0.04,1.04 ± 0.03,and 1.07 ± 0.05,respectively,in HepG2(P > 0.05).When the cells were cultured simultaneously with Glycer-AGE and MK615,MK615 abrogated the proliferative effect of Glycer-AGE in HuH7.CONCLUSION:Only Glycer-AGE has a proliferative effect on HuH7,which expresses a higher level of RAGE.MK615 suppresses the proliferative effect of GlycerAGE on HuH7 by decreasing the expression of RAGE.
文摘AIM： To investigate the hepatoprotective effect of MK615, a Japanese apricot extract, in an animal model, and its clinical therapeutic effect. METHODS： Wistar rats were administered physiologi- cal saline （4 mL/kg） or MK615 solution （4 mL/kg） for 7 d. On the sixth d, acute hepatic injury was induced by administering a single intraperitoneal injection （ip） of D-galactosamine hydrochloride （D-GaIN） （600 mg/kg）. Plasma levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined, and liver tissues were used for histopathological analy- sis. Fifty-eight patients with liver disorders [hepatitis C （n = 40）, non-alcoholic fatty liver disease （n = 15）, and autoimmune liver disease （n = 3）] were orally admin- istered commercially available Misatol ME-containing MK615 （13 g/d） daily for 12 wk. Blood and urine were sampled immediately before and 6 wk, 12 wk, and 16 wk after the start of intake to measure various bio- chemical parameters. The percentage change in ALT and AST levels after 12 wk from the pre-intake baseline served as a primary endpoint. RESULTS： D-GaIN effectively induced acute hepatic injury in the rats. At 48 h after the ip injection of D-GaIN, the plasma levels of ALT （475.6 ：t： 191.5 IU/L vs 225.3 ＋ 194.2 IU/L, P 〈 0.05） and AST （1253.9：1：223.4 IU/L vs 621.9 ＋ 478.2 IU/L, P 〈 0.05） in the MK615 group were significantly lower than the control group. Scattered single cell necrosis, loss of hepatocytes, and extensive inflammatory cell infiltration were observed in hepatic tissue samples collected from the control group. However, these findings were less pronounced in the group receiving MK615. At the end of the clinical study, serum ALT and AST levels were significantly de- creased compared with pre-intake baseline levels from 103.5 ：l： 58.8 IU/L to 71.8 ＋ 39.3 IU/L （P 〈 0.05） and from 93.5 ：E 55.6 IU/L to 65.5 ＋ 34.8 IU/L （P 〈 0.05）, respectively. A reduction of 〉~ 30% from the pre-study baseline ALT level was observed in 26 （45%） of the 58 patients, while 25 （43%） patients exhibited similar AST level reductions. The chronic hepatitis C group exhibit- ed significant ALT and AST level reductions from 93.4：1： 51.1 IU/L to 64.6 ＋ 35.1 IU/L （P 〈 0.05） and from 94.2 ＋ 55.5 IU/L to 67.2：1：35.6 IU/L （P 〈 0.05）, respective- ly. A reduction of 〉~ 30% from the pre-study baseline ALT level was observed in 20 （50%） of the 40 patients.ALT levels in both the combined ursodeoxycholic acid （UDCA） treatment and the UDCA uncombined groups were significantly lower after Misatol ME administration. MK615 protected hepatocytes from D-GaiN-induced cytotoxicity in rats. Misatol ME decreased elevated ALT and AST levels in patients with liver disorders. CONCLUSION： These results suggest that MK615 and Misatol ME are promising hepatoprotective agents for patients with liver disorders.
