Combination of thiol antioxidant Silibinin with Brostallicin is associated with increase in the anti-apoptotic protein Bcl-2 and decrease in caspase 3 activity

Pook, Sim-Hwee; Toh, Chee-Keong; Mahendran, Ratha

doi:10.1016/j.canlet.2005.07.002

Cited by 12 publications

(10 citation statements)

References 14 publications

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“…The literature data show that at higher concentrations of silybin (> 100 μM) and exposure longer than 24 h, an apparent inhibition of cell growth with no cytotoxic effect occurred. (Varghese et al 2005, Pook et al 2006, Lah et al 2007, Chen et al 2009, Angeli et al 2010. Comparing the silybin EC 50 results, value over 34 times (LDH assay), 18 times (CBB assy) and 10 times (MTT) higher than the EC 50 values for lasalocid were recorded.…”

Section: Discussionmentioning

confidence: 86%

“…All in vitro studies indicated a lack of cytotoxicity of silybin (Antonio et al 1991, Oh et al 2004, Varghese et al 2005, Dvorak et al 2006, Pook et al 2006, Angeli et al 2010, Radko et al 2011. Using cytotoxicity tests, we showed that silybin in concentrations above 25 μM led to decrease of viability and growth inhibition of HepG2 cell lines after 24 h incubation.…”

Section: Discussionmentioning

confidence: 99%

“…However, silybin enhances the therapeutic potential of anticancer drugs such as doxorubicin, cisplatin, carboplatin and baicalein by synergistic effects for cell growth inhibition (Tyagi et al 2004, Chen et al 2009). The determination of either synergism or antagonism is probably an intricate balance between the concentration and type of anti-oxidants used, the class of chemotherapeutic agents administered as well as the category of cell involved (Pook et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The literature on HepG2 cell line proved it to be a good model of cytotoxicity assessment impacted by xenobiotics, as well as to estimate an interaction nature. (Ponsoda et al 1995, Thabrew et al 1997, Pook et al 2006, Clothier et al 2008, Chen et al 2009). …”

mentioning

confidence: 99%

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Cytoprotective effect of silybin against lasalocid-induced toxicity in HepG2 cells

Radko¹,

Cybulski²,

Rzeski³

2013

Polish Journal of Veterinary Sciences

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Lasalocid is an ionophore coccidiostatic agent frequently used in poultry. Its extensive use causes the formation of residues in edible tissues and eggs which may pose a risk to consumers. Silybin is the main compound extracted from the herb milk thistle Silybum marianum and its hepatoprotective effect has been reported in literature.The aim of the study was to compare lasalocid and silybin cytotoxic effects followed by their combined use in HepG2 cell line. A cytoprotective effect resulting from the interaction of both pharmacologically active substances was measured.In this study, an MTT test, coomassie brillant blue binding test, and LDH release test determined the effective concentration (EC 50 ) of the compounds. The isobolograms and combination index were used to assess the nature of interaction.The lowest EC 50 -value for lasalocid was established via the MTT test. This study revealed a lack of silybin cytotoxic effect on the cells. Co-actions of the two drugs led to a significant decrease of lasalocid cytotoxicity. The isobolograms and combination index showed a remarkable antagonistic effect in the course of silybin and lasalocid interaction.The results indicate that silybin revealed a cytoprotective effect when incubated with lasalocid since its cytotoxic impact on HepG2 cells has been significantly diminished.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Cytoprotective effect of silybin against lasalocid-induced toxicity in HepG2 cells

Radko¹,

Cybulski²,

Rzeski³

2013

Polish Journal of Veterinary Sciences

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“…In vitro and in vivo experiments show that it is active against a variety of experimental murine and human tumors when used as a single agent. It also displays synergistic activity when combined with either mechanistically classical or novel molecular-targeted drugs (2,3). Brostallicin circumvents tumor resistance mechanisms known to inactivate alkylating agents, platinum derivatives, and camptothecins, maintains efficacy in mismatch repairdeficient cells, and is very active in inducing apoptosis (3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Role of Glutathione Transferases in the Mechanism of Brostallicin Activation

Pezzola

Antonini²,

Geroni

et al. 2009

Biochemistry

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Brostallicin is a novel and unique glutathione transferase-activated pro-drug with promising anticancer activity, currently in phase I and II clinical evaluation. In this work, we show that, in comparison with the parental cell line showing low GST levels, the cytotoxic activity of brostallicin is significantly enhanced in the human breast carcinoma MCF-7 cell line, transfected with either human GST-π or GST-μ. Moreover, we describe in detail the interaction of brostallicin with GSH in the presence of GSTP1-1 and GSTM2-2, the predominant GST isoenzymes found within tumor cells. The experiments reported here indicate that brostallicin binds reversibly to both isoenzymes with K d values in the micromolar range (the affinity being higher for GSTM2-2). Direct evidence that both GSTP1-1 and GSTM2-2 isoenzymes catalyze the Michael addition reaction of GSH to brostallicin has been obtained both by an HPLC-MS technique and by a new fluorometric assay. We also saw the rapid formation of an intermediate reactive species, which is slowly converted into the final products. This intermediate, identified as the R-chloroamido derivative of the GSH-brostallicin adduct, is able to alkylate DNA in a sequence-specific manner and appears to be the active form of the drug. The kinetic behavior of the reaction between brostallicin and GSH, catalyzed by GSTP1-1, has been studied in detail, and a minimum kinetic scheme that suitably describes the experimental data is provided. Overall, these data fully support and extend the findings that brostallicin could be indicated for the treatment of tumor overexpressing the pi or mu class GST.

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Silybum marianum (L.) Gaertn: the Source of Silymarin

Corchete

2008

Bioactive Molecules and Medicinal Plants

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Combination of thiol antioxidant Silibinin with Brostallicin is associated with increase in the anti-apoptotic protein Bcl-2 and decrease in caspase 3 activity

Cited by 12 publications

References 14 publications

Cytoprotective effect of silybin against lasalocid-induced toxicity in HepG2 cells

Cytoprotective effect of silybin against lasalocid-induced toxicity in HepG2 cells

Role of Glutathione Transferases in the Mechanism of Brostallicin Activation

Silybum marianum (L.) Gaertn: the Source of Silymarin

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