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Kazem Nejatikoshki - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of htert gene expression by silibinin loaded plga peg fe3o4 in t47d breast cancer cell line
    BioImpacts : BI, 2013
    Co-Authors: Zohreh Ebrahimnezhad, Nosratollah Zarghami, Manoutchehr Keyhani, Soumaye Amirsaadat, Abolfazl Akbarzadeh, Mohammad Rahmati, Zohreh Mohammad Taheri, Kazem Nejatikoshki
    Abstract:

    Introduction: Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from the milk Thistle Plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effect of this nanodrug on Telomerase gene expression. Methods: The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then, the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl Thiazol Tetrazolium (MTT) assay. After that, inhibition of Telomerase gene expression was indicated through Real-time PCR. Results: Data analysis from MTT assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG-Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the level of telomerase gene expression more efficiently decreased with silibinin-loaded PLGA-PEG-Fe3O4 than with free silibinin alone. Conclusion: The present study indicates that this nanodrug causes down-regulation of Telomerase gene expression in cancer cells. Therefore, PLGA-PEG-Fe3O4 could be an appropriate carrier for hydrophobic agents such as silibinin to improve their action in cancer therapy.

Richard L. Whelan - One of the best experts on this subject based on the ideXlab platform.

  • Perioperative polyphenon E- and siliphos-inhibited colorectal tumor growth and metastases without impairment of gastric or abdominal wound healing in mouse models
    Surgical Endoscopy, 2012
    Co-Authors: Xiaohong Yan, Thomas R. Gardner, Michael Grieco, Sonali A. C. Herath, Joon Ho Jang, Daniel D. Kirchoff, Linda Njoh, Samer Naffouje, H. M. C. Shantha Kumara, Richard L. Whelan
    Abstract:

    Introduction Perioperative anticancer therapy that does not impair wound healing is needed to counter the persistent proangiogenic plasma compositional changes that occur after colorectal resection. Polyphenon E (PolyE), a green tea derivative (main component EGCG), and Siliphos (main component silibinin), from the milk Thistle Plant, both have antitumor effects. This study assessed the impact of PolyE/Siliphos (PES) on wound healing and the growth of CT-26 colon cancer in several murine models. Methods One wound healing and three tumor studies were performed. Tumor Study (TS)1 assessed the impact of PES on subcutaneous tumor growth, whereas TS2 assessed PES’s impact on subcutaneous growth when given pre- and post-CO_2 pneumoperitoneum (pneumo), sham laparotomy, or anesthesia alone. TS3 determined the ability of PES to limit hepatic metastases (mets) after portal venous injection of tumor cells. In the final study, laparotomy and gastrotomy wound healing were assessed several ways. BALB/c mice were used for all studies. The drugs were given via drinking water (PolyE) and gavage (Siliphos), daily, for 7–9 days preprocedure and for 7–21 days postoperatively. Tumor mass, number/size of hepatic mets, and proliferation and apoptosis rates were assessed. The abdominal breaking strength and energy to failure were measured postmortem as was gastric bursting pressures. Results PES significantly inhibited subcutaneous growth in the nonoperative setting. PES also significantly decreased the number/size of liver mets when given perioperatively. Abdominal wound breaking strength, energy to wound failure, and collagen content were not altered by PES; gastrotomy bursting strength also was not affected by PES. Neither drug alone had a significant impact on tumor growth. Conclusions The PES combination inhibited subcutaneous and hepatic tumor growth yet did not impair wound healing. PES holds promise as a perioperative anticancer therapy.

  • Perioperative polyphenon E- and siliphos-inhibited colorectal tumor growth and metastases without impairment of gastric or abdominal wound healing in mouse models.
    Surgical Endoscopy, 2012
    Co-Authors: Xiaohong Yan, Thomas R. Gardner, Michael Grieco, Sonali A. C. Herath, Joon Ho Jang, Daniel D. Kirchoff, Linda Njoh, H. M. C. Shantha Kumara, Samer Naffouje, Richard L. Whelan
    Abstract:

    Introduction Perioperative anticancer therapy that does not impair wound healing is needed to counter the persistent proangiogenic plasma compositional changes that occur after colorectal resection. Polyphenon E (PolyE), a green tea derivative (main component EGCG), and Siliphos (main component silibinin), from the milk Thistle Plant, both have antitumor effects. This study assessed the impact of PolyE/Siliphos (PES) on wound healing and the growth of CT-26 colon cancer in several murine models.

Francis Raul - One of the best experts on this subject based on the ideXlab platform.

  • The flavonolignan silibinin potentiates TRAIL-induced apoptosis in human colon adenocarcinoma and in derived TRAIL-resistant metastatic cells
    Apoptosis, 2012
    Co-Authors: Henriette Kauntz, Souad Bousserouel, Francine Gossé, Francis Raul
    Abstract:

    Silibinin, a flavonolignan, is the major active component of the milk Thistle Plant ( Silybum marianum ) and has been shown to possess anti-neoplastic properties. TNF-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent which selectively induces apoptosis in cancer cells. However, resistance to TRAIL-induced apoptosis is an important and frequent problem in cancer treatment. In this study, we investigated the effect of silibinin and TRAIL in an in vitro model of human colon cancer progression, consisting of primary colon tumor cells (SW480) and their derived TRAIL-resistant metastatic cells (SW620). We showed by flow cytometry that silibinin and TRAIL synergistically induced cell death in the two cell lines. Up-regulation of death receptor 4 (DR4) and DR5 by silibinin was shown by RT-PCR and by flow cytometry. Human recombinant DR5/Fc chimera protein that has a dominant-negative effect by competing with the endogenous receptors abrogated cell death induced by silibinin and TRAIL, demonstrating the activation of the death receptor pathway. Synergistic activation of caspase-3, -8, and -9 by silibinin and TRAIL was shown by colorimetric assays. When caspase inhibitors were used, cell death was blocked. Furthermore, silibinin and TRAIL potentiated activation of the mitochondrial apoptotic pathway and down-regulated the anti-apoptotic proteins Mcl-1 and XIAP. The involvement of XIAP in sensitization of the two cell lines to TRAIL was demonstrated using the XIAP inhibitor embelin. These findings demonstrate the synergistic action of silibinin and TRAIL, suggesting chemopreventive and therapeutic potential which should be further explored.

  • Silibinin triggers apoptotic signaling pathways and autophagic survival response in human colon adenocarcinoma cells and their derived metastatic cells
    Apoptosis, 2011
    Co-Authors: Henriette Kauntz, Souad Bousserouel, Francine Gossé, Francis Raul
    Abstract:

    Silibinin, a flavonolignan isolated from the milk Thistle Plant ( Silybum marianum ), possesses anti-neoplastic properties. In vitro and in vivo studies have recently shown that silibinin inhibits the growth of colorectal cancer (CRC). The present study investigates the mechanisms of silibinin-induced cell death using an in vitro model of human colon cancer progression, consisting of primary tumor cells (SW480) and their derived metastatic cells (SW620) isolated from a metastasis of the same patient. Silibinin induced apoptotic cell death evidenced by DNA fragmentation and activation of caspase-3 in both cell lines. Silibinin enhanced the expression (protein and mRNA) of TNF-related apoptosis-inducing ligand (TRAIL) death receptors (DR4/DR5) at the cell surface in SW480 cells, and induced their expression in TRAIL-resistant SW620 cells normally not expressing DR4/DR5. Caspase-8 and -10 were activated demonstrating the involvement of the extrinsic apoptotic pathway in silibinin-treated SW480 and SW620 cells. The protein Bid was cleaved in SW480 cells indicating a cross-talk between extrinsic and intrinsic apoptotic pathway. We demonstrated that silibinin activated also the intrinsic apoptotic pathway in both cell lines, including the perturbation of the mitochondrial membrane potential, the release of cytochrome c into the cytosol and the activation of caspase-9. Simultaneously to apoptosis, silibinin triggered an autophagic response. The inhibition of autophagy with a specific inhibitor enhanced cell death, suggesting a cytoprotective function for autophagy in silibinin-treated cells. Taken together, our data show that silibinin initiated in SW480 and SW620 cells an autophagic-mediated survival response overwhelmed by the activation of both the extrinsic and intrinsic apoptotic pathways.

Zohreh Ebrahimnezhad - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of htert gene expression by silibinin loaded plga peg fe3o4 in t47d breast cancer cell line
    BioImpacts : BI, 2013
    Co-Authors: Zohreh Ebrahimnezhad, Nosratollah Zarghami, Manoutchehr Keyhani, Soumaye Amirsaadat, Abolfazl Akbarzadeh, Mohammad Rahmati, Zohreh Mohammad Taheri, Kazem Nejatikoshki
    Abstract:

    Introduction: Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from the milk Thistle Plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effect of this nanodrug on Telomerase gene expression. Methods: The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then, the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl Thiazol Tetrazolium (MTT) assay. After that, inhibition of Telomerase gene expression was indicated through Real-time PCR. Results: Data analysis from MTT assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG-Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the level of telomerase gene expression more efficiently decreased with silibinin-loaded PLGA-PEG-Fe3O4 than with free silibinin alone. Conclusion: The present study indicates that this nanodrug causes down-regulation of Telomerase gene expression in cancer cells. Therefore, PLGA-PEG-Fe3O4 could be an appropriate carrier for hydrophobic agents such as silibinin to improve their action in cancer therapy.

Xiaohong Yan - One of the best experts on this subject based on the ideXlab platform.

  • Perioperative polyphenon E- and siliphos-inhibited colorectal tumor growth and metastases without impairment of gastric or abdominal wound healing in mouse models
    Surgical Endoscopy, 2012
    Co-Authors: Xiaohong Yan, Thomas R. Gardner, Michael Grieco, Sonali A. C. Herath, Joon Ho Jang, Daniel D. Kirchoff, Linda Njoh, Samer Naffouje, H. M. C. Shantha Kumara, Richard L. Whelan
    Abstract:

    Introduction Perioperative anticancer therapy that does not impair wound healing is needed to counter the persistent proangiogenic plasma compositional changes that occur after colorectal resection. Polyphenon E (PolyE), a green tea derivative (main component EGCG), and Siliphos (main component silibinin), from the milk Thistle Plant, both have antitumor effects. This study assessed the impact of PolyE/Siliphos (PES) on wound healing and the growth of CT-26 colon cancer in several murine models. Methods One wound healing and three tumor studies were performed. Tumor Study (TS)1 assessed the impact of PES on subcutaneous tumor growth, whereas TS2 assessed PES’s impact on subcutaneous growth when given pre- and post-CO_2 pneumoperitoneum (pneumo), sham laparotomy, or anesthesia alone. TS3 determined the ability of PES to limit hepatic metastases (mets) after portal venous injection of tumor cells. In the final study, laparotomy and gastrotomy wound healing were assessed several ways. BALB/c mice were used for all studies. The drugs were given via drinking water (PolyE) and gavage (Siliphos), daily, for 7–9 days preprocedure and for 7–21 days postoperatively. Tumor mass, number/size of hepatic mets, and proliferation and apoptosis rates were assessed. The abdominal breaking strength and energy to failure were measured postmortem as was gastric bursting pressures. Results PES significantly inhibited subcutaneous growth in the nonoperative setting. PES also significantly decreased the number/size of liver mets when given perioperatively. Abdominal wound breaking strength, energy to wound failure, and collagen content were not altered by PES; gastrotomy bursting strength also was not affected by PES. Neither drug alone had a significant impact on tumor growth. Conclusions The PES combination inhibited subcutaneous and hepatic tumor growth yet did not impair wound healing. PES holds promise as a perioperative anticancer therapy.

  • Perioperative polyphenon E- and siliphos-inhibited colorectal tumor growth and metastases without impairment of gastric or abdominal wound healing in mouse models.
    Surgical Endoscopy, 2012
    Co-Authors: Xiaohong Yan, Thomas R. Gardner, Michael Grieco, Sonali A. C. Herath, Joon Ho Jang, Daniel D. Kirchoff, Linda Njoh, H. M. C. Shantha Kumara, Samer Naffouje, Richard L. Whelan
    Abstract:

    Introduction Perioperative anticancer therapy that does not impair wound healing is needed to counter the persistent proangiogenic plasma compositional changes that occur after colorectal resection. Polyphenon E (PolyE), a green tea derivative (main component EGCG), and Siliphos (main component silibinin), from the milk Thistle Plant, both have antitumor effects. This study assessed the impact of PolyE/Siliphos (PES) on wound healing and the growth of CT-26 colon cancer in several murine models.