The Experts below are selected from a list of 3471 Experts worldwide ranked by ideXlab platform
Yung Hyun Choi - One of the best experts on this subject based on the ideXlab platform.
-
Sanguinarine induces apoptosis of human oral squamous cell carcinoma kb cells via inactivation of the pi3k akt signaling pathway
Drug Development Research, 2016Co-Authors: Tae Kyung Lee, Gi Young Kim, Cheol Park, Wunjae Kim, Soonjeong Jeong, Moonjin Jeong, Yung Hyun ChoiAbstract:Preclinical Research Sanguinarine, an alkaloid isolated from the root of Sanguinaria canadensis and other plants of the Papaveraceae family, selectively induces apoptotic cell death in a variety of human cancer cells, but its mechanism of action requires further elaboration. The present study investigated the pro-apoptotic effects of Sanguinarine in human oral squamous cell carcinoma KB cells. Sanguinarine treatment increased DR5/TRAILR2 (death receptor 5/TRAIL receptor 2) expression and enhanced the activation of caspase-8 and cleavage of its substrate, Bid. Sanguinarine also induced the mitochondrial translocation of pro-apoptotic Bax, mitochondrial dysfunction, cytochrome c release to the cytosol, and activation of caspase-9 and -3. However, a pan-caspase inhibitor, z-VAD-fmk, reversed the growth inhibition and apoptosis induced by Sanguinarine. Sanguinarine also suppressed the phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt in KB cells, while co-treatment of cells with Sanguinarine and a PI3K inhibitor revealed synergistic apoptotic effects. However, pharmacological inhibition of AMP-activated protein kinase and mitogen-activated protein kinases did not reduce or enhance Sanguinarine-induced growth inhibition and apoptosis. Collectively, these findings indicate that the pro-apoptotic effects of Sanguinarine in KB cells may be regulated by a caspase-dependent cascade via activation of both intrinsic and extrinsic signaling pathways and inactivation of PI3K/Akt signaling. Drug Dev Res 77 : 227–240, 2016. © 2016 Wiley Periodicals, Inc.
-
Sanguinarine induces apoptosis in human colorectal cancer hct 116 cells through ros mediated egr 1 activation and mitochondrial dysfunction
Toxicology Letters, 2013Co-Authors: Min Ho Han, Gi Young Kim, Young Hyun Yoo, Yung Hyun ChoiAbstract:We examined the effects of Sanguinarine, a benzophenanthridine alkaloid, on reactive oxygen species (ROS) production and the association of these effects with apoptotic cell death in a human colorectal cancer HCT-116 cell line. Sanguinarine generated ROS, which was followed by a decrease in the mitochondrial membrane potential (MMP), the activation of caspase-9 and -3, and the down-regulation of anti-apoptotic proteins, such as Bcl2, XIAP and cIAP-1. Sanguinarine also promoted the activation of caspase-8 and truncation of Bid (tBid). However, the quenching of ROS generation by N-acetyl-l-cysteine, a scavenger of ROS, reversed the Sanguinarine-induced apoptosis effects via inhibition of the MMP collapse, tBid expression, and activation of caspases. Sanguinarine also markedly induced the expression of the early growth response gene-1 (Egr-1) during the early period, after which expression level was decreased. In addition, HCT-116 cells transfected with Egr-1 siRNA displayed significant blockage of Sanguinarine-induced apoptotic activity in a ROS-dependent manner. These observations clearly indicate that ROS, which are key mediators of Egr-1 activation and MMP collapse, are involved in the early molecular events in the Sanguinarine-induced apoptotic pathway acting in HCT-116 cells.
-
apoptosis induction of human bladder cancer cells by Sanguinarine through reactive oxygen species mediated up regulation of early growth response gene 1
PLOS ONE, 2013Co-Authors: Min Ho Han, Gi Young Kim, Cheol Park, Chengyun Jin, Youngchae Chang, Sungkwon Moon, Wunjae Kim, Yung Hyun ChoiAbstract:Although the effects of Sanguinarine, a benzophenanthridine alkaloid, on the inhibition of some kinds of cancer cell growth have been established, the underlying mechanisms are not completely understood. This study investigated possible mechanisms by which Sanguinarine exerts its anticancer action in cultured human bladder cancer cell lines (T24, EJ, and 5637). Sanguinarine treatment resulted in concentration-response growth inhibition of the bladder cancer cells by inducing apoptosis. Sanguinarine-induced apoptosis was correlated with the up-regulation of Bax, the down-regulation of Bid and XIAP, the activation of caspases (-3, -8, and -9), and the generation of increased reactive oxygen species (ROS). The ROS scavenger N-acetyl cysteine (NAC) completely reversed the Sanguinarine-triggered apoptotic events. In addition, Sanguinarine effectively increased the activation of the c-Jun N-terminal kinase (JNK) and the expression of the early growth response gene-1 (Egr-1), which was recovered by pretreatment with NAC. Furthermore, knockdown of Egr-1 expression by small interfering RNA attenuated Sanguinarine-induced apoptosis, but not the JNK inhibitor, indicating that the interception of ROS generation blocked the Sanguinarine-induced apoptotic effects via deregulation of the expression of Egr-1 proteins. Taken together, the data provide evidence that Sanguinarine is a potent anticancer agent, which inhibits the growth of bladder cancer cells and induces their apoptosis through the generation of free radicals.
-
Induction of apoptosis by Sanguinarine in C6 rat glioblastoma cells is associated with the modulation of the Bcl-2 family and activation of caspases through downregulation of extracellular signal-regulated kinase and Akt.
Anti-Cancer Drugs, 2007Co-Authors: Min Ho Han, Wonho Lee, Taeg Kyu Kwon, Sung Ok Kim, Gi Young Kim, Byung Tae Choi, Yung Hyun ChoiAbstract:Sanguinarine is a benzophenanthridine alkaloid that is derived from the root of Sanguinaria canadensis and other poppy fumaria species, and is known to have antimicrobial, antiinflammatory and antioxidant properties. This study investigated the possible mechanisms through which Sanguinarine exerts its antiproliferative action in cultured C6 rat glioblastoma cells. The exposure of C6 cells to Sanguinarine resulted in growth inhibition and the induction of apoptosis in a dose-dependent manner, as measured by the MTT assay, fluorescence microscopy, agarose gel electrophoresis and annexin-V-based assay. The Sanguinarine treatment induced the proteolytic activation of caspases and ICAD/DFF45, which was associated with the modulation of the Bcl-2 family, concomitant degradation of poly(ADP ribose) polymerase and phospholipase C-gamma1 protein, and DNA fragmentation. z-DEVD-fmk, a caspase-3-specific inhibitor, blocked poly(ADP ribose) polymerase degradation, DNA fragmentation and increased the survival rate of Sanguinarine-treated C6 cells. Moreover, the activity of extracellular signal-regulated kinase and Akt was downregulated in Sanguinarine-treated cells, and PD98059, a specific extracellular signal-regulated kinase inhibitor, and phosphatidylinositol 3'-kinase/Akt inhibitors, LY294002 and wortmanin, sensitized the cells to Sanguinarine-induced apoptosis, indicating that the downregulation of the extracellular signal-regulated kinase and Akt signaling pathway may play a key role in Sanguinarine-induced apoptosis in C6 cells.
Gi Young Kim - One of the best experts on this subject based on the ideXlab platform.
-
Sanguinarine induces apoptosis of human oral squamous cell carcinoma kb cells via inactivation of the pi3k akt signaling pathway
Drug Development Research, 2016Co-Authors: Tae Kyung Lee, Gi Young Kim, Cheol Park, Wunjae Kim, Soonjeong Jeong, Moonjin Jeong, Yung Hyun ChoiAbstract:Preclinical Research Sanguinarine, an alkaloid isolated from the root of Sanguinaria canadensis and other plants of the Papaveraceae family, selectively induces apoptotic cell death in a variety of human cancer cells, but its mechanism of action requires further elaboration. The present study investigated the pro-apoptotic effects of Sanguinarine in human oral squamous cell carcinoma KB cells. Sanguinarine treatment increased DR5/TRAILR2 (death receptor 5/TRAIL receptor 2) expression and enhanced the activation of caspase-8 and cleavage of its substrate, Bid. Sanguinarine also induced the mitochondrial translocation of pro-apoptotic Bax, mitochondrial dysfunction, cytochrome c release to the cytosol, and activation of caspase-9 and -3. However, a pan-caspase inhibitor, z-VAD-fmk, reversed the growth inhibition and apoptosis induced by Sanguinarine. Sanguinarine also suppressed the phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt in KB cells, while co-treatment of cells with Sanguinarine and a PI3K inhibitor revealed synergistic apoptotic effects. However, pharmacological inhibition of AMP-activated protein kinase and mitogen-activated protein kinases did not reduce or enhance Sanguinarine-induced growth inhibition and apoptosis. Collectively, these findings indicate that the pro-apoptotic effects of Sanguinarine in KB cells may be regulated by a caspase-dependent cascade via activation of both intrinsic and extrinsic signaling pathways and inactivation of PI3K/Akt signaling. Drug Dev Res 77 : 227–240, 2016. © 2016 Wiley Periodicals, Inc.
-
Sanguinarine induces apoptosis in human colorectal cancer hct 116 cells through ros mediated egr 1 activation and mitochondrial dysfunction
Toxicology Letters, 2013Co-Authors: Min Ho Han, Gi Young Kim, Young Hyun Yoo, Yung Hyun ChoiAbstract:We examined the effects of Sanguinarine, a benzophenanthridine alkaloid, on reactive oxygen species (ROS) production and the association of these effects with apoptotic cell death in a human colorectal cancer HCT-116 cell line. Sanguinarine generated ROS, which was followed by a decrease in the mitochondrial membrane potential (MMP), the activation of caspase-9 and -3, and the down-regulation of anti-apoptotic proteins, such as Bcl2, XIAP and cIAP-1. Sanguinarine also promoted the activation of caspase-8 and truncation of Bid (tBid). However, the quenching of ROS generation by N-acetyl-l-cysteine, a scavenger of ROS, reversed the Sanguinarine-induced apoptosis effects via inhibition of the MMP collapse, tBid expression, and activation of caspases. Sanguinarine also markedly induced the expression of the early growth response gene-1 (Egr-1) during the early period, after which expression level was decreased. In addition, HCT-116 cells transfected with Egr-1 siRNA displayed significant blockage of Sanguinarine-induced apoptotic activity in a ROS-dependent manner. These observations clearly indicate that ROS, which are key mediators of Egr-1 activation and MMP collapse, are involved in the early molecular events in the Sanguinarine-induced apoptotic pathway acting in HCT-116 cells.
-
apoptosis induction of human bladder cancer cells by Sanguinarine through reactive oxygen species mediated up regulation of early growth response gene 1
PLOS ONE, 2013Co-Authors: Min Ho Han, Gi Young Kim, Cheol Park, Chengyun Jin, Youngchae Chang, Sungkwon Moon, Wunjae Kim, Yung Hyun ChoiAbstract:Although the effects of Sanguinarine, a benzophenanthridine alkaloid, on the inhibition of some kinds of cancer cell growth have been established, the underlying mechanisms are not completely understood. This study investigated possible mechanisms by which Sanguinarine exerts its anticancer action in cultured human bladder cancer cell lines (T24, EJ, and 5637). Sanguinarine treatment resulted in concentration-response growth inhibition of the bladder cancer cells by inducing apoptosis. Sanguinarine-induced apoptosis was correlated with the up-regulation of Bax, the down-regulation of Bid and XIAP, the activation of caspases (-3, -8, and -9), and the generation of increased reactive oxygen species (ROS). The ROS scavenger N-acetyl cysteine (NAC) completely reversed the Sanguinarine-triggered apoptotic events. In addition, Sanguinarine effectively increased the activation of the c-Jun N-terminal kinase (JNK) and the expression of the early growth response gene-1 (Egr-1), which was recovered by pretreatment with NAC. Furthermore, knockdown of Egr-1 expression by small interfering RNA attenuated Sanguinarine-induced apoptosis, but not the JNK inhibitor, indicating that the interception of ROS generation blocked the Sanguinarine-induced apoptotic effects via deregulation of the expression of Egr-1 proteins. Taken together, the data provide evidence that Sanguinarine is a potent anticancer agent, which inhibits the growth of bladder cancer cells and induces their apoptosis through the generation of free radicals.
-
Induction of apoptosis by Sanguinarine in C6 rat glioblastoma cells is associated with the modulation of the Bcl-2 family and activation of caspases through downregulation of extracellular signal-regulated kinase and Akt.
Anti-Cancer Drugs, 2007Co-Authors: Min Ho Han, Wonho Lee, Taeg Kyu Kwon, Sung Ok Kim, Gi Young Kim, Byung Tae Choi, Yung Hyun ChoiAbstract:Sanguinarine is a benzophenanthridine alkaloid that is derived from the root of Sanguinaria canadensis and other poppy fumaria species, and is known to have antimicrobial, antiinflammatory and antioxidant properties. This study investigated the possible mechanisms through which Sanguinarine exerts its antiproliferative action in cultured C6 rat glioblastoma cells. The exposure of C6 cells to Sanguinarine resulted in growth inhibition and the induction of apoptosis in a dose-dependent manner, as measured by the MTT assay, fluorescence microscopy, agarose gel electrophoresis and annexin-V-based assay. The Sanguinarine treatment induced the proteolytic activation of caspases and ICAD/DFF45, which was associated with the modulation of the Bcl-2 family, concomitant degradation of poly(ADP ribose) polymerase and phospholipase C-gamma1 protein, and DNA fragmentation. z-DEVD-fmk, a caspase-3-specific inhibitor, blocked poly(ADP ribose) polymerase degradation, DNA fragmentation and increased the survival rate of Sanguinarine-treated C6 cells. Moreover, the activity of extracellular signal-regulated kinase and Akt was downregulated in Sanguinarine-treated cells, and PD98059, a specific extracellular signal-regulated kinase inhibitor, and phosphatidylinositol 3'-kinase/Akt inhibitors, LY294002 and wortmanin, sensitized the cells to Sanguinarine-induced apoptosis, indicating that the downregulation of the extracellular signal-regulated kinase and Akt signaling pathway may play a key role in Sanguinarine-induced apoptosis in C6 cells.
Min Ho Han - One of the best experts on this subject based on the ideXlab platform.
-
Sanguinarine induces apoptosis in human colorectal cancer hct 116 cells through ros mediated egr 1 activation and mitochondrial dysfunction
Toxicology Letters, 2013Co-Authors: Min Ho Han, Gi Young Kim, Young Hyun Yoo, Yung Hyun ChoiAbstract:We examined the effects of Sanguinarine, a benzophenanthridine alkaloid, on reactive oxygen species (ROS) production and the association of these effects with apoptotic cell death in a human colorectal cancer HCT-116 cell line. Sanguinarine generated ROS, which was followed by a decrease in the mitochondrial membrane potential (MMP), the activation of caspase-9 and -3, and the down-regulation of anti-apoptotic proteins, such as Bcl2, XIAP and cIAP-1. Sanguinarine also promoted the activation of caspase-8 and truncation of Bid (tBid). However, the quenching of ROS generation by N-acetyl-l-cysteine, a scavenger of ROS, reversed the Sanguinarine-induced apoptosis effects via inhibition of the MMP collapse, tBid expression, and activation of caspases. Sanguinarine also markedly induced the expression of the early growth response gene-1 (Egr-1) during the early period, after which expression level was decreased. In addition, HCT-116 cells transfected with Egr-1 siRNA displayed significant blockage of Sanguinarine-induced apoptotic activity in a ROS-dependent manner. These observations clearly indicate that ROS, which are key mediators of Egr-1 activation and MMP collapse, are involved in the early molecular events in the Sanguinarine-induced apoptotic pathway acting in HCT-116 cells.
-
apoptosis induction of human bladder cancer cells by Sanguinarine through reactive oxygen species mediated up regulation of early growth response gene 1
PLOS ONE, 2013Co-Authors: Min Ho Han, Gi Young Kim, Cheol Park, Chengyun Jin, Youngchae Chang, Sungkwon Moon, Wunjae Kim, Yung Hyun ChoiAbstract:Although the effects of Sanguinarine, a benzophenanthridine alkaloid, on the inhibition of some kinds of cancer cell growth have been established, the underlying mechanisms are not completely understood. This study investigated possible mechanisms by which Sanguinarine exerts its anticancer action in cultured human bladder cancer cell lines (T24, EJ, and 5637). Sanguinarine treatment resulted in concentration-response growth inhibition of the bladder cancer cells by inducing apoptosis. Sanguinarine-induced apoptosis was correlated with the up-regulation of Bax, the down-regulation of Bid and XIAP, the activation of caspases (-3, -8, and -9), and the generation of increased reactive oxygen species (ROS). The ROS scavenger N-acetyl cysteine (NAC) completely reversed the Sanguinarine-triggered apoptotic events. In addition, Sanguinarine effectively increased the activation of the c-Jun N-terminal kinase (JNK) and the expression of the early growth response gene-1 (Egr-1), which was recovered by pretreatment with NAC. Furthermore, knockdown of Egr-1 expression by small interfering RNA attenuated Sanguinarine-induced apoptosis, but not the JNK inhibitor, indicating that the interception of ROS generation blocked the Sanguinarine-induced apoptotic effects via deregulation of the expression of Egr-1 proteins. Taken together, the data provide evidence that Sanguinarine is a potent anticancer agent, which inhibits the growth of bladder cancer cells and induces their apoptosis through the generation of free radicals.
-
Induction of apoptosis by Sanguinarine in C6 rat glioblastoma cells is associated with the modulation of the Bcl-2 family and activation of caspases through downregulation of extracellular signal-regulated kinase and Akt.
Anti-Cancer Drugs, 2007Co-Authors: Min Ho Han, Wonho Lee, Taeg Kyu Kwon, Sung Ok Kim, Gi Young Kim, Byung Tae Choi, Yung Hyun ChoiAbstract:Sanguinarine is a benzophenanthridine alkaloid that is derived from the root of Sanguinaria canadensis and other poppy fumaria species, and is known to have antimicrobial, antiinflammatory and antioxidant properties. This study investigated the possible mechanisms through which Sanguinarine exerts its antiproliferative action in cultured C6 rat glioblastoma cells. The exposure of C6 cells to Sanguinarine resulted in growth inhibition and the induction of apoptosis in a dose-dependent manner, as measured by the MTT assay, fluorescence microscopy, agarose gel electrophoresis and annexin-V-based assay. The Sanguinarine treatment induced the proteolytic activation of caspases and ICAD/DFF45, which was associated with the modulation of the Bcl-2 family, concomitant degradation of poly(ADP ribose) polymerase and phospholipase C-gamma1 protein, and DNA fragmentation. z-DEVD-fmk, a caspase-3-specific inhibitor, blocked poly(ADP ribose) polymerase degradation, DNA fragmentation and increased the survival rate of Sanguinarine-treated C6 cells. Moreover, the activity of extracellular signal-regulated kinase and Akt was downregulated in Sanguinarine-treated cells, and PD98059, a specific extracellular signal-regulated kinase inhibitor, and phosphatidylinositol 3'-kinase/Akt inhibitors, LY294002 and wortmanin, sensitized the cells to Sanguinarine-induced apoptosis, indicating that the downregulation of the extracellular signal-regulated kinase and Akt signaling pathway may play a key role in Sanguinarine-induced apoptosis in C6 cells.
Edward Perkins - One of the best experts on this subject based on the ideXlab platform.
-
Disruption of nucleocytoplasmic trafficking of cyclin D1 and topoisomerase II by Sanguinarine
BMC cell biology, 2006Co-Authors: Jon M Holy, Genelle Lamont, Edward PerkinsAbstract:The quaternary isoquinoline alkaloid Sanguinarine is receiving increasing attention as a potential chemotherapeutic agent in the treatment of cancer. Previous studies have shown that this DNA-binding phytochemical can arrest a number of different types of transformed cells in G0/G1, and upregulate the CKIs p21 and p27 while downregulating multiple cyclins and CDKs. To more closely examine the responses of some of these cell cycle regulatory molecules to Sanguinarine, we used immunocytochemical methods to visualize cyclin D1 and topoisomerase II behavior in MCF-7 breast cancer cells. 5 – 10 μM Sanguinarine effectively inhibits MCF-7 proliferation after a single application of drug. This growth inhibition is accompanied by a striking relocalization of cyclin D1 and topoisomerase II from the nucleus to the cytoplasm, and this effect persists for at least three days after drug addition. DNA synthesis is transiently inhibited by Sanguinarine, but cells recover their ability to synthesize DNA within 24 hours. Taking advantage of the fluorescence characteristics of Sanguinarine to follow its uptake and distribution suggests that these effects arise from a window of activity of a few hours immediately after drug addition, when Sanguinarine is concentrated in the nucleus. These effects occur in morphologically healthy-looking cells, and thus do not simply represent part of an apoptotic response. It appears that sub-apoptotic concentrations of Sanguinarine can suppress breast cancer cell proliferation for extended lengths of time, and that this effect results from a relatively brief period of activity when the drug is concentrated in the nucleus. Sanguinarine transiently inhibits DNA synthesis, but a novel mechanism of action appears to involve disrupting the trafficking of a number of molecules involved in cell cycle regulation and progression. The ability of sub-apoptotic concentrations of Sanguinarine to inhibit cell growth may be a useful feature for potential chemotherapeutic applications; however, a narrow effective range for these effects may exist.
-
Disruption of nucleocytoplasmic trafficking of cyclin D1 and topoisomerase II by Sanguinarine
BMC Cell Biology, 2006Co-Authors: Jon Holy, Genelle Lamont, Edward PerkinsAbstract:Background The quaternary isoquinoline alkaloid Sanguinarine is receiving increasing attention as a potential chemotherapeutic agent in the treatment of cancer. Previous studies have shown that this DNA-binding phytochemical can arrest a number of different types of transformed cells in G0/G1, and upregulate the CKIs p21 and p27 while downregulating multiple cyclins and CDKs. To more closely examine the responses of some of these cell cycle regulatory molecules to Sanguinarine, we used immunocytochemical methods to visualize cyclin D1 and topoisomerase II behavior in MCF-7 breast cancer cells. Results 5 – 10 μM Sanguinarine effectively inhibits MCF-7 proliferation after a single application of drug. This growth inhibition is accompanied by a striking relocalization of cyclin D1 and topoisomerase II from the nucleus to the cytoplasm, and this effect persists for at least three days after drug addition. DNA synthesis is transiently inhibited by Sanguinarine, but cells recover their ability to synthesize DNA within 24 hours. Taking advantage of the fluorescence characteristics of Sanguinarine to follow its uptake and distribution suggests that these effects arise from a window of activity of a few hours immediately after drug addition, when Sanguinarine is concentrated in the nucleus. These effects occur in morphologically healthy-looking cells, and thus do not simply represent part of an apoptotic response. Conclusion It appears that sub-apoptotic concentrations of Sanguinarine can suppress breast cancer cell proliferation for extended lengths of time, and that this effect results from a relatively brief period of activity when the drug is concentrated in the nucleus. Sanguinarine transiently inhibits DNA synthesis, but a novel mechanism of action appears to involve disrupting the trafficking of a number of molecules involved in cell cycle regulation and progression. The ability of sub-apoptotic concentrations of Sanguinarine to inhibit cell growth may be a useful feature for potential chemotherapeutic applications; however, a narrow effective range for these effects may exist.
Jiiang-huei Jeng - One of the best experts on this subject based on the ideXlab platform.
-
induction of necrosis and apoptosis to kb cancer cells by Sanguinarine is associated with reactive oxygen species production and mitochondrial membrane depolarization
Toxicology and Applied Pharmacology, 2007Co-Authors: Meichi Chang, Bor-ru Lin, Po Hsuen Lee, Ying Jan Wang, Chiupo Chan, Lini Chen, Yiling Tsai, Yinlin Wang, Jiiang-huei JengAbstract:Abstract Sanguinarine is a benzopheanthridine alkaloid present in the root of Sanguinaria canadensis L. and Chellidonium majus L. In this study, Sanguinarine (2 and 3 μM) exhibited cytotoxicity to KB cancer cells by decreasing MTT reduction to 83% and 52% of control after 24-h of exposure. Sanguinarine also inhibited the colony forming capacity (> 52–58%) and growth of KB cancer cells at concentrations higher than 0.5–1 μM. Short-term exposure to Sanguinarine (> 0.5 μM) effectively suppressed the adhesion of KB cells to collagen and fibronectin (FN). Sanguinarine (2 and 3 μM) induced evident apoptosis as indicated by an increase in sub-G0/G1 populations, which was detected after 6-h of exposure. Only a slight increase in cells arresting in S-phase and G2/M was noted. Induction of KB cell apoptosis and necrosis by Sanguinarine (2 and 3 μM) was further confirmed by Annexin V-PI dual staining flow cytometry and the presence of DNA fragmentation. The cytotoxicity by Sanguinarine was accompanied by an increase in production of reactive oxygen species (ROS) and depolarization of mitochondrial membrane potential as indicated by single cell flow cytometric analysis of DCF and rhodamine fluorescence. NAC (1 and 3 mM) and catalase (2000 U/ml) prevented the Sanguinarine-induced ROS production and cytotoxicity, whereas dimethylthiourea (DMT) showed no marked preventive effect. These results suggest that Sanguinarine has anticarcinogenic properties with induction of ROS production and mitochondrial membrane depolarization, which mediate cancer cell death.
-
Antiplatelet effect of Sanguinarine is correlated to calcium mobilization, thromboxane and cAMP production.
Atherosclerosis, 2006Co-Authors: Jiiang-huei Jeng, Bor-ru Lin, Wan-hong Lan, Hsiao Hwa Chang, Po Hsuen Lee, Ying Jan Wang, Juo Song Wang, Yi-jane ChenAbstract:Sanguinarine is a plant alkaloid present in the root of Sanguinaria canadensis and Poppy fumaria species. Sanguinarine has been used as an antiseptic mouth rinse and a toothpaste additive to reduce dental plaque and gingival inflammation. In this study, we investigated the antiplatelet effects of Sanguinarine, aiming to extend its potential pharmacological applications. Sanguinarine inhibited platelet aggregation induced by arachidonic acid (AA), collagen, U46619 and sub-threshold concentration of thrombin (0.05 U/ml) with IC(50) concentrations of 8.3, 7.7, 8.6 and 4.4 microM, respectively. Sanguinarine (5-10 microM) inhibited 10-31% of platelet TXB(2) production, but not platelet aggregation induced by higher concentration of thrombin (0.1 U/ml). SQ29548, a thromboxane receptor antagonist, inhibited the AA-induced platelet aggregation but not TXB(2) production. Sanguinarine suppressed cyclooxygenase-1 (COX-1) activity (IC(50)=28 microM), whereas its effect on COX-2 activity was minimal. Sanguinarine (8, 10 microM) further inhibited the AA-induced Ca(2+) mobilization by 27-62%. In addition, SQ22536, an adenylate cyclase inhibitor, attenuated the inhibitory effect of Sanguinarine toward AA-induced platelet Ca(2+) mobilization and aggregation. These results suggest that Sanguinarine is a potent antiplatelet agent, which activates adenylate cyclase, inhibits platelet Ca(2+) mobilization, TXB(2) production as well as suppresses COX-1 enzyme activity. Sanguinarine may have therapeutic potential for treatment of cardiovascular diseases related to platelet aggregation.
