The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Ghorban Mohammadzadeh - One of the best experts on this subject based on the ideXlab platform.
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Specific targeting of HER2-positive human breast carcinoma SK-BR-3 cells by Amygdaline-Z_HER2 affibody conjugate
Molecular Biology Reports, 2020Co-Authors: Bahman Moradipoodeh, Mostafa Jamalan, Majid Zeinali, Masood Fereidoonnezhad, Ghorban MohammadzadehAbstract:Amygdalin induces apoptotic death in several carcinoma cells. Affibody is an engineered protein with a high affinity for human epidermal receptor 2 (HER2). We assessed the cytotoxic effects of the Amygdalin-Z_HER2 affibody conjugate on two breast carcinoma cell lines. The Z_HER2 affibody gene was synthesized and transferred into E. coli BL21 as an expression host. After purification, the Z_HER2 affibody was conjugated to Amygdalin. The cytotoxic effects of Amygdalin and its Z_HER2 affibody conjugate on the SK-BR-3, with overexpression of HER2, and MCF-7 cells were evaluated by MTT assay. The effects of Amygdalin and its conjugate on apoptotic death and expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were measured. Amygdalin individually showed a potent cytotoxic effect against both MCF-7 (IC_50 = 14.2 mg ml^−1) and SK-BR-3 cells (IC_50 = 13.7 mg ml^−1). However, the Amygdalin-Z_HER2 affibody conjugate had a more cytotoxic effect on SK-BR-3 (IC_50 = 8.27 mg ml^−1) than MCF-7 cells (IC_50 = 19.8 mg ml^−1). Amygdalin had a significant apoptotic effect on both cell lines and the effect of its conjugate on SK-BR-3 cells was significantly more potent than MCF-7 cells. Amygdalin increased Bax and decreased Bcl-2 expression in both cell lines. However, the effect of its conjugate on the Bax and Bcl-2 expression in SK-BR-3 was more potent than MCF-7 cells. In conclusion, the Amygdalin-Z_HER2 affibody conjugate may be considered as a valuable candidate for specific treatment of breast cancer patients with overexpression of HER2. However, further in vivo studies are required to explain the antitumoral effects of constructed Amygdalin-Z_HER2 affibody conjugate.
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Specific targeting of HER2-positive human breast carcinoma SK-BR-3 cells by Amygdaline-Z_HER2 affibody conjugate
Molecular Biology Reports, 2020Co-Authors: Bahman Moradipoodeh, Mostafa Jamalan, Majid Zeinali, Masood Fereidoonnezhad, Ghorban MohammadzadehAbstract:Amygdalin induces apoptotic death in several carcinoma cells. Affibody is an engineered protein with a high affinity for human epidermal receptor 2 (HER2). We assessed the cytotoxic effects of the Amygdalin-Z_HER2 affibody conjugate on two breast carcinoma cell lines. The Z_HER2 affibody gene was synthesized and transferred into E. coli BL21 as an expression host. After purification, the Z_HER2 affibody was conjugated to Amygdalin. The cytotoxic effects of Amygdalin and its Z_HER2 affibody conjugate on the SK-BR-3, with overexpression of HER2, and MCF-7 cells were evaluated by MTT assay. The effects of Amygdalin and its conjugate on apoptotic death and expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were measured. Amygdalin individually showed a potent cytotoxic effect against both MCF-7 (IC_50 = 14.2 mg ml^−1) and SK-BR-3 cells (IC_50 = 13.7 mg ml^−1). However, the Amygdalin-Z_HER2 affibody conjugate had a more cytotoxic effect on SK-BR-3 (IC_50 = 8.27 mg ml^−1) than MCF-7 cells (IC_50 = 19.8 mg ml^−1). Amygdalin had a significant apoptotic effect on both cell lines and the effect of its conjugate on SK-BR-3 cells was significantly more potent than MCF-7 cells. Amygdalin increased Bax and decreased Bcl-2 expression in both cell lines. However, the effect of its conjugate on the Bax and Bcl-2 expression in SK-BR-3 was more potent than MCF-7 cells. In conclusion, the Amygdalin-Z_HER2 affibody conjugate may be considered as a valuable candidate for specific treatment of breast cancer patients with overexpression of HER2. However, further in vivo studies are required to explain the antitumoral effects of constructed Amygdalin-Z_HER2 affibody conjugate.
Roman A. Blaheta - One of the best experts on this subject based on the ideXlab platform.
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Amygdalin Modulates Prostate Cancer Cell Adhesion and Migration In Vitro.
Nutrition and cancer, 2019Co-Authors: Jens Mani, Jochen Rutz, Sebastian Maxeiner, Eva Juengel, Frederik Roos, Felix K.-h. Chun, Jens Neuschäfer, Christian Resch, Roman A. BlahetaAbstract:The natural compound, Amygdalin, is notably popular with prostate cancer patients as an alternative or complementary treatment option. However, knowledge about its mode of action is sparse. We investigated Amygdalin's impact on prostate cancer adhesion and motile behavior. DU-145 and PC3 cancer cells were exposed to Amygdalin. Adhesion to human vascular endothelium or immobilized collagen was then explored. The influence of Amygdalin on chemotaxis and migration was also investigated, as well as Amygdalin induced alteration to surface and total cellular α and β integrin expression. Integrin knockdown was performed to evaluate the integrin influence on chemotaxis and adhesion. Amygdalin significantly reduced chemotactic activity, migration, and adhesion of DU-145 but not of PC3 cells. Amygdalin elevated integrin α2 in both cell lines. Integrin α6 was reduced by Amygdalin only in DU-145 cells, whereas β1 increased only in PC3 cells. Functional blocking revealed a negative association of α2 with PC3 and DU-145 chemotaxis. The β1 increase correlated with enhanced chemotaxis, the diminished α6 expression with reduced chemotaxis. Amygdalin acted on prostate cancer cells in vitro. It induced downregulation of α6 integrin in DU-145 but not in PC3 cells, suggesting that exposing certain prostate cancer cells to Amygdalin might inhibit metastatic spread promoted by this particular integrin.
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Cyanide and lactate levels in patients during chronic oral Amygdalin intake followed by intravenous Amygdalin administration
Complementary therapies in medicine, 2019Co-Authors: Jens Mani, Jochen Rutz, Sebastian Maxeiner, Eva Juengel, Dimitra Bon, Frederik Roos, Felix K.-h. Chun, Roman A. BlahetaAbstract:Abstract The natural compound Amygdalin has gained high popularity among tumor patients as a complementary or alternative treatment option. However, due to metabolization of Amygdalin to cyanide (HCN) following oral consumption, there could be a high risk of lactic acidosis caused by cyanide intoxication. The present retrospective study was undertaken to evaluate cyanide blood and lactate plasma levels of tumor patients (n = 55) before and after intravenous (i.v.) Amygdalin infusion. All patients had also continuously ingested Amygdalin tablets (3 x 500 mg/day), excepting on the days of i.v. administration. Each patient received one to five intravenous Amygdalin treatments. The time period between each i.v. application ranged between 4–6 days. The initial i.v. dose was 6 mg (n = 28), 9 mg (n = 1), 15 mg (n = 1) or 18 mg (n = 25). The mean cyanide blood level before i.v. Amygdalin administration was 34.74 μg/L, which increased significantly to a mean value of 66.20 μg/L after i. v. Amygdalin application. In contrast, lactate decreased significantly from 1266 μmol/L pre-infusion to 868 μmol/L post-infusion. Increasing i.v. Amygdalin by 1 mg was also associated with a significant increase in the cyanide level, while the lactate blood level significantly decreased. This is the first study evaluating cyanide levels under conditions employed by Amygdalin administrators, i.e. after chronic oral Amygdalin intake and then again after a closely subsequent intravenous Amygdalin administration. Since lactate decreased, whilst cyanide increased, it is concluded that elevation of cyanide does not induce metabolic acidosis in terms of an increased lactate level.
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Amygdalin blocks the in vitro adhesion and invasion of renal cell carcinoma cells by an integrin dependent mechanism
International Journal of Molecular Medicine, 2016Co-Authors: Eva Juengel, Jens Mani, Jochen Rutz, Igor Tsaur, Karen Nelson, Axel Haferkamp, Masud Afschar, Jasmina Makarevic, Roman A. BlahetaAbstract:Information about the natural compound Amygdalin, which is employed as an antitumor agent, is sparse and thus its efficacy remains controversial. In this study, to determine whether Amygdalin exerts antitumor effects on renal cell carcinoma (RCC) cells, its impact on RCC metastatic activity was investigated. The RCC cell lines, Caki-1, KTC-26 and A498, were exposed to Amygdalin from apricot kernels, and adhesion to human vascular endothelium, immobilized collagen or fibronectin was investigated. The influence of Amygdalin on chemotactic and invasive activity was also determined, as was the influence of Amygdalin on surface and total cellular α and β integrin expression, which are involved in metastasis. We noted that Amygdalin caused significant reductions in chemotactic activity, invasion and adhesion to endothelium, collagen and fibronectin. Using FACScan analysis, we noted that Amygdalin also induced reductions, particularly in integrins α5 and α6, in all three cell lines. Functional blocking of α5 resulted in significantly diminished adhesion of KTC-26 and A498 to collagen and also in decreased chemotactic behavior in all three cell lines. Blocking α6 integrin significantly reduced chemotactic activity in all three cell lines. Thus, we suggest that exposing RCC cells to Amygdalin inhibits metastatic spread and is associated with downregulation of α5 and α6 integrins. Therefore, we posit that Amygdalin exerts antitumor activity in vitro, and this may be linked to integrin regulation.
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Amygdalin, quackery or cure?
Phytomedicine : international journal of phytotherapy and phytopharmacology, 2016Co-Authors: Roman A. Blaheta, Karen Nelson, Axel Haferkamp, Eva JuengelAbstract:Abstract Background The cyanogenic diglucoside, Amygdalin, has gained high popularity among cancer patients together with, or in place of, conventional therapy. Still, evidence based research on Amygdalin is sparse and its benefit controversial. Purpose Since so many cancer patients consume Amygdalin, and many clinicians administer it without clear knowledge of its mode of action, current knowledge has been summarized and the pros and cons of its use weighed. Methods A retrospective analysis was conducted for Amygdalin relevant reports using the PubMed database with the main search term “Amygdalin” or “laetrile”, at times combined with “cancer”, “patient”, “cyanide” or “toxic”. We did not exclude any “unwanted” articles. Additionally, internet sources authorized by governmental or national institutions have also been included. Sections Individual chapters summarize pharmacokinetics, preclinical and clinical studies and toxicity. Conclusion No convincing evidence showing that Amygdalin induces rapid, distinct tumor regression in cancer patients, particularly in those with late-stage disease, is apparent. However, there is also no evidence that purified Amygdalin, administered in "therapeutic" dosage, causes toxicity. Multiple aspects of Amygdalin administration have not yet been adequately explored, making further investigation necessary to evaluate its actual therapeutic potential.
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Amygdalin inhibits the growth of renal cell carcinoma cells in vitro
International Journal of Molecular Medicine, 2016Co-Authors: Eva Juengel, Jochen Rutz, Igor Tsaur, Karen Nelson, Axel Haferkamp, Jasmina Makarevic, Anita Thomas, Roman A. BlahetaAbstract:Although Amygdalin is used by many cancer patients as an antitumor agent, there is a lack of information on the efficacy and toxicity of this natural compound. In the present study, the inhibitory effect of Amygdalin on the growth of renal cell carcinoma (RCC) cells was examined. Amygdalin (10 mg/ml) was applied to the RCC cell lines, Caki-1, KTC-26 and A498, for 24 h or 2 weeks. Untreated cells served as controls. Tumor cell growth and proliferation were determined using MTT and BrdU tests, and cell cycle phases were evaluated. Expression of the cell cycle activating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1 and D3 as well as of the cell cycle inhibiting proteins p19 and p27 was examined by western blot analysis. Surface expression of the differentiation markers E- and N-cadherin was also investigated. Functional blockade by siRNA was used to determine the impact of several proteins on tumor cell growth. Amygdalin treatment caused a significant reduction in RCC cell growth and proliferation. This effect was correlated with a reduced percentage of G2/M-phase RCC cells and an increased percentage of cells in the G0/1-phase (Caki-1 and A498) or cell cycle arrest in the S-phase (KTC-26). Furthermore, Amygdalin induced a marked decrease in cell cycle activating proteins, in particular cdk1 and cyclin B. Functional blocking of cdk1 and cyclin B resulted in significantly diminished tumor cell growth in all three RCC cell lines. Aside from its inhibitory effects on growth, Amygdalin also modulated the differentiation markers, E- and N-cadherin. Hence, exposing RCC cells to Amygdalin inhibited cell cycle progression and tumor cell growth by impairing cdk1 and cyclin B expression. Moreover, we noted that Amygdalin affected differentiation markers. Thus, we suggest that Amygdalin exerted RCC antitumor effects in vitro.
Bahman Moradipoodeh - One of the best experts on this subject based on the ideXlab platform.
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Specific targeting of HER2-positive human breast carcinoma SK-BR-3 cells by Amygdaline-Z_HER2 affibody conjugate
Molecular Biology Reports, 2020Co-Authors: Bahman Moradipoodeh, Mostafa Jamalan, Majid Zeinali, Masood Fereidoonnezhad, Ghorban MohammadzadehAbstract:Amygdalin induces apoptotic death in several carcinoma cells. Affibody is an engineered protein with a high affinity for human epidermal receptor 2 (HER2). We assessed the cytotoxic effects of the Amygdalin-Z_HER2 affibody conjugate on two breast carcinoma cell lines. The Z_HER2 affibody gene was synthesized and transferred into E. coli BL21 as an expression host. After purification, the Z_HER2 affibody was conjugated to Amygdalin. The cytotoxic effects of Amygdalin and its Z_HER2 affibody conjugate on the SK-BR-3, with overexpression of HER2, and MCF-7 cells were evaluated by MTT assay. The effects of Amygdalin and its conjugate on apoptotic death and expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were measured. Amygdalin individually showed a potent cytotoxic effect against both MCF-7 (IC_50 = 14.2 mg ml^−1) and SK-BR-3 cells (IC_50 = 13.7 mg ml^−1). However, the Amygdalin-Z_HER2 affibody conjugate had a more cytotoxic effect on SK-BR-3 (IC_50 = 8.27 mg ml^−1) than MCF-7 cells (IC_50 = 19.8 mg ml^−1). Amygdalin had a significant apoptotic effect on both cell lines and the effect of its conjugate on SK-BR-3 cells was significantly more potent than MCF-7 cells. Amygdalin increased Bax and decreased Bcl-2 expression in both cell lines. However, the effect of its conjugate on the Bax and Bcl-2 expression in SK-BR-3 was more potent than MCF-7 cells. In conclusion, the Amygdalin-Z_HER2 affibody conjugate may be considered as a valuable candidate for specific treatment of breast cancer patients with overexpression of HER2. However, further in vivo studies are required to explain the antitumoral effects of constructed Amygdalin-Z_HER2 affibody conjugate.
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Specific targeting of HER2-positive human breast carcinoma SK-BR-3 cells by Amygdaline-Z_HER2 affibody conjugate
Molecular Biology Reports, 2020Co-Authors: Bahman Moradipoodeh, Mostafa Jamalan, Majid Zeinali, Masood Fereidoonnezhad, Ghorban MohammadzadehAbstract:Amygdalin induces apoptotic death in several carcinoma cells. Affibody is an engineered protein with a high affinity for human epidermal receptor 2 (HER2). We assessed the cytotoxic effects of the Amygdalin-Z_HER2 affibody conjugate on two breast carcinoma cell lines. The Z_HER2 affibody gene was synthesized and transferred into E. coli BL21 as an expression host. After purification, the Z_HER2 affibody was conjugated to Amygdalin. The cytotoxic effects of Amygdalin and its Z_HER2 affibody conjugate on the SK-BR-3, with overexpression of HER2, and MCF-7 cells were evaluated by MTT assay. The effects of Amygdalin and its conjugate on apoptotic death and expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were measured. Amygdalin individually showed a potent cytotoxic effect against both MCF-7 (IC_50 = 14.2 mg ml^−1) and SK-BR-3 cells (IC_50 = 13.7 mg ml^−1). However, the Amygdalin-Z_HER2 affibody conjugate had a more cytotoxic effect on SK-BR-3 (IC_50 = 8.27 mg ml^−1) than MCF-7 cells (IC_50 = 19.8 mg ml^−1). Amygdalin had a significant apoptotic effect on both cell lines and the effect of its conjugate on SK-BR-3 cells was significantly more potent than MCF-7 cells. Amygdalin increased Bax and decreased Bcl-2 expression in both cell lines. However, the effect of its conjugate on the Bax and Bcl-2 expression in SK-BR-3 was more potent than MCF-7 cells. In conclusion, the Amygdalin-Z_HER2 affibody conjugate may be considered as a valuable candidate for specific treatment of breast cancer patients with overexpression of HER2. However, further in vivo studies are required to explain the antitumoral effects of constructed Amygdalin-Z_HER2 affibody conjugate.
Eva Juengel - One of the best experts on this subject based on the ideXlab platform.
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Amygdalin Modulates Prostate Cancer Cell Adhesion and Migration In Vitro.
Nutrition and cancer, 2019Co-Authors: Jens Mani, Jochen Rutz, Sebastian Maxeiner, Eva Juengel, Frederik Roos, Felix K.-h. Chun, Jens Neuschäfer, Christian Resch, Roman A. BlahetaAbstract:The natural compound, Amygdalin, is notably popular with prostate cancer patients as an alternative or complementary treatment option. However, knowledge about its mode of action is sparse. We investigated Amygdalin's impact on prostate cancer adhesion and motile behavior. DU-145 and PC3 cancer cells were exposed to Amygdalin. Adhesion to human vascular endothelium or immobilized collagen was then explored. The influence of Amygdalin on chemotaxis and migration was also investigated, as well as Amygdalin induced alteration to surface and total cellular α and β integrin expression. Integrin knockdown was performed to evaluate the integrin influence on chemotaxis and adhesion. Amygdalin significantly reduced chemotactic activity, migration, and adhesion of DU-145 but not of PC3 cells. Amygdalin elevated integrin α2 in both cell lines. Integrin α6 was reduced by Amygdalin only in DU-145 cells, whereas β1 increased only in PC3 cells. Functional blocking revealed a negative association of α2 with PC3 and DU-145 chemotaxis. The β1 increase correlated with enhanced chemotaxis, the diminished α6 expression with reduced chemotaxis. Amygdalin acted on prostate cancer cells in vitro. It induced downregulation of α6 integrin in DU-145 but not in PC3 cells, suggesting that exposing certain prostate cancer cells to Amygdalin might inhibit metastatic spread promoted by this particular integrin.
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Cyanide and lactate levels in patients during chronic oral Amygdalin intake followed by intravenous Amygdalin administration
Complementary therapies in medicine, 2019Co-Authors: Jens Mani, Jochen Rutz, Sebastian Maxeiner, Eva Juengel, Dimitra Bon, Frederik Roos, Felix K.-h. Chun, Roman A. BlahetaAbstract:Abstract The natural compound Amygdalin has gained high popularity among tumor patients as a complementary or alternative treatment option. However, due to metabolization of Amygdalin to cyanide (HCN) following oral consumption, there could be a high risk of lactic acidosis caused by cyanide intoxication. The present retrospective study was undertaken to evaluate cyanide blood and lactate plasma levels of tumor patients (n = 55) before and after intravenous (i.v.) Amygdalin infusion. All patients had also continuously ingested Amygdalin tablets (3 x 500 mg/day), excepting on the days of i.v. administration. Each patient received one to five intravenous Amygdalin treatments. The time period between each i.v. application ranged between 4–6 days. The initial i.v. dose was 6 mg (n = 28), 9 mg (n = 1), 15 mg (n = 1) or 18 mg (n = 25). The mean cyanide blood level before i.v. Amygdalin administration was 34.74 μg/L, which increased significantly to a mean value of 66.20 μg/L after i. v. Amygdalin application. In contrast, lactate decreased significantly from 1266 μmol/L pre-infusion to 868 μmol/L post-infusion. Increasing i.v. Amygdalin by 1 mg was also associated with a significant increase in the cyanide level, while the lactate blood level significantly decreased. This is the first study evaluating cyanide levels under conditions employed by Amygdalin administrators, i.e. after chronic oral Amygdalin intake and then again after a closely subsequent intravenous Amygdalin administration. Since lactate decreased, whilst cyanide increased, it is concluded that elevation of cyanide does not induce metabolic acidosis in terms of an increased lactate level.
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Amygdalin blocks the in vitro adhesion and invasion of renal cell carcinoma cells by an integrin dependent mechanism
International Journal of Molecular Medicine, 2016Co-Authors: Eva Juengel, Jens Mani, Jochen Rutz, Igor Tsaur, Karen Nelson, Axel Haferkamp, Masud Afschar, Jasmina Makarevic, Roman A. BlahetaAbstract:Information about the natural compound Amygdalin, which is employed as an antitumor agent, is sparse and thus its efficacy remains controversial. In this study, to determine whether Amygdalin exerts antitumor effects on renal cell carcinoma (RCC) cells, its impact on RCC metastatic activity was investigated. The RCC cell lines, Caki-1, KTC-26 and A498, were exposed to Amygdalin from apricot kernels, and adhesion to human vascular endothelium, immobilized collagen or fibronectin was investigated. The influence of Amygdalin on chemotactic and invasive activity was also determined, as was the influence of Amygdalin on surface and total cellular α and β integrin expression, which are involved in metastasis. We noted that Amygdalin caused significant reductions in chemotactic activity, invasion and adhesion to endothelium, collagen and fibronectin. Using FACScan analysis, we noted that Amygdalin also induced reductions, particularly in integrins α5 and α6, in all three cell lines. Functional blocking of α5 resulted in significantly diminished adhesion of KTC-26 and A498 to collagen and also in decreased chemotactic behavior in all three cell lines. Blocking α6 integrin significantly reduced chemotactic activity in all three cell lines. Thus, we suggest that exposing RCC cells to Amygdalin inhibits metastatic spread and is associated with downregulation of α5 and α6 integrins. Therefore, we posit that Amygdalin exerts antitumor activity in vitro, and this may be linked to integrin regulation.
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Amygdalin, quackery or cure?
Phytomedicine : international journal of phytotherapy and phytopharmacology, 2016Co-Authors: Roman A. Blaheta, Karen Nelson, Axel Haferkamp, Eva JuengelAbstract:Abstract Background The cyanogenic diglucoside, Amygdalin, has gained high popularity among cancer patients together with, or in place of, conventional therapy. Still, evidence based research on Amygdalin is sparse and its benefit controversial. Purpose Since so many cancer patients consume Amygdalin, and many clinicians administer it without clear knowledge of its mode of action, current knowledge has been summarized and the pros and cons of its use weighed. Methods A retrospective analysis was conducted for Amygdalin relevant reports using the PubMed database with the main search term “Amygdalin” or “laetrile”, at times combined with “cancer”, “patient”, “cyanide” or “toxic”. We did not exclude any “unwanted” articles. Additionally, internet sources authorized by governmental or national institutions have also been included. Sections Individual chapters summarize pharmacokinetics, preclinical and clinical studies and toxicity. Conclusion No convincing evidence showing that Amygdalin induces rapid, distinct tumor regression in cancer patients, particularly in those with late-stage disease, is apparent. However, there is also no evidence that purified Amygdalin, administered in "therapeutic" dosage, causes toxicity. Multiple aspects of Amygdalin administration have not yet been adequately explored, making further investigation necessary to evaluate its actual therapeutic potential.
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Amygdalin inhibits the growth of renal cell carcinoma cells in vitro
International Journal of Molecular Medicine, 2016Co-Authors: Eva Juengel, Jochen Rutz, Igor Tsaur, Karen Nelson, Axel Haferkamp, Jasmina Makarevic, Anita Thomas, Roman A. BlahetaAbstract:Although Amygdalin is used by many cancer patients as an antitumor agent, there is a lack of information on the efficacy and toxicity of this natural compound. In the present study, the inhibitory effect of Amygdalin on the growth of renal cell carcinoma (RCC) cells was examined. Amygdalin (10 mg/ml) was applied to the RCC cell lines, Caki-1, KTC-26 and A498, for 24 h or 2 weeks. Untreated cells served as controls. Tumor cell growth and proliferation were determined using MTT and BrdU tests, and cell cycle phases were evaluated. Expression of the cell cycle activating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1 and D3 as well as of the cell cycle inhibiting proteins p19 and p27 was examined by western blot analysis. Surface expression of the differentiation markers E- and N-cadherin was also investigated. Functional blockade by siRNA was used to determine the impact of several proteins on tumor cell growth. Amygdalin treatment caused a significant reduction in RCC cell growth and proliferation. This effect was correlated with a reduced percentage of G2/M-phase RCC cells and an increased percentage of cells in the G0/1-phase (Caki-1 and A498) or cell cycle arrest in the S-phase (KTC-26). Furthermore, Amygdalin induced a marked decrease in cell cycle activating proteins, in particular cdk1 and cyclin B. Functional blocking of cdk1 and cyclin B resulted in significantly diminished tumor cell growth in all three RCC cell lines. Aside from its inhibitory effects on growth, Amygdalin also modulated the differentiation markers, E- and N-cadherin. Hence, exposing RCC cells to Amygdalin inhibited cell cycle progression and tumor cell growth by impairing cdk1 and cyclin B expression. Moreover, we noted that Amygdalin affected differentiation markers. Thus, we suggest that Amygdalin exerted RCC antitumor effects in vitro.
Masood Fereidoonnezhad - One of the best experts on this subject based on the ideXlab platform.
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Specific targeting of HER2-positive human breast carcinoma SK-BR-3 cells by Amygdaline-Z_HER2 affibody conjugate
Molecular Biology Reports, 2020Co-Authors: Bahman Moradipoodeh, Mostafa Jamalan, Majid Zeinali, Masood Fereidoonnezhad, Ghorban MohammadzadehAbstract:Amygdalin induces apoptotic death in several carcinoma cells. Affibody is an engineered protein with a high affinity for human epidermal receptor 2 (HER2). We assessed the cytotoxic effects of the Amygdalin-Z_HER2 affibody conjugate on two breast carcinoma cell lines. The Z_HER2 affibody gene was synthesized and transferred into E. coli BL21 as an expression host. After purification, the Z_HER2 affibody was conjugated to Amygdalin. The cytotoxic effects of Amygdalin and its Z_HER2 affibody conjugate on the SK-BR-3, with overexpression of HER2, and MCF-7 cells were evaluated by MTT assay. The effects of Amygdalin and its conjugate on apoptotic death and expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were measured. Amygdalin individually showed a potent cytotoxic effect against both MCF-7 (IC_50 = 14.2 mg ml^−1) and SK-BR-3 cells (IC_50 = 13.7 mg ml^−1). However, the Amygdalin-Z_HER2 affibody conjugate had a more cytotoxic effect on SK-BR-3 (IC_50 = 8.27 mg ml^−1) than MCF-7 cells (IC_50 = 19.8 mg ml^−1). Amygdalin had a significant apoptotic effect on both cell lines and the effect of its conjugate on SK-BR-3 cells was significantly more potent than MCF-7 cells. Amygdalin increased Bax and decreased Bcl-2 expression in both cell lines. However, the effect of its conjugate on the Bax and Bcl-2 expression in SK-BR-3 was more potent than MCF-7 cells. In conclusion, the Amygdalin-Z_HER2 affibody conjugate may be considered as a valuable candidate for specific treatment of breast cancer patients with overexpression of HER2. However, further in vivo studies are required to explain the antitumoral effects of constructed Amygdalin-Z_HER2 affibody conjugate.
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Specific targeting of HER2-positive human breast carcinoma SK-BR-3 cells by Amygdaline-Z_HER2 affibody conjugate
Molecular Biology Reports, 2020Co-Authors: Bahman Moradipoodeh, Mostafa Jamalan, Majid Zeinali, Masood Fereidoonnezhad, Ghorban MohammadzadehAbstract:Amygdalin induces apoptotic death in several carcinoma cells. Affibody is an engineered protein with a high affinity for human epidermal receptor 2 (HER2). We assessed the cytotoxic effects of the Amygdalin-Z_HER2 affibody conjugate on two breast carcinoma cell lines. The Z_HER2 affibody gene was synthesized and transferred into E. coli BL21 as an expression host. After purification, the Z_HER2 affibody was conjugated to Amygdalin. The cytotoxic effects of Amygdalin and its Z_HER2 affibody conjugate on the SK-BR-3, with overexpression of HER2, and MCF-7 cells were evaluated by MTT assay. The effects of Amygdalin and its conjugate on apoptotic death and expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were measured. Amygdalin individually showed a potent cytotoxic effect against both MCF-7 (IC_50 = 14.2 mg ml^−1) and SK-BR-3 cells (IC_50 = 13.7 mg ml^−1). However, the Amygdalin-Z_HER2 affibody conjugate had a more cytotoxic effect on SK-BR-3 (IC_50 = 8.27 mg ml^−1) than MCF-7 cells (IC_50 = 19.8 mg ml^−1). Amygdalin had a significant apoptotic effect on both cell lines and the effect of its conjugate on SK-BR-3 cells was significantly more potent than MCF-7 cells. Amygdalin increased Bax and decreased Bcl-2 expression in both cell lines. However, the effect of its conjugate on the Bax and Bcl-2 expression in SK-BR-3 was more potent than MCF-7 cells. In conclusion, the Amygdalin-Z_HER2 affibody conjugate may be considered as a valuable candidate for specific treatment of breast cancer patients with overexpression of HER2. However, further in vivo studies are required to explain the antitumoral effects of constructed Amygdalin-Z_HER2 affibody conjugate.
