Effect of Silibinin on the Growth and Progression of Primary Lung Tumors in Mice

Singh, Rana P.; Deep, Gagan; Chittezhath, Manesh; Kaur, Manjinder; Dwyer‐Nield, Lori D.; Malkinson, Alvin M.; Agarwal, Rajesh

doi:10.1093/jnci/djj231

Cited by 151 publications

(156 citation statements)

References 31 publications

Supporting

Mentioning

146

Contrasting

Unclassified

Order By: Relevance

“…20 Silibinin possesses strong anticancer efficacy against both carcinogen-induced primary lung tumors and chemotherapy resistant lung tumor xenografts, where it decreased tumor incidence, inhibited tumor growth and progression by downregulating inducible nitric oxide synthase and Cox-2 mediated signaling, and overcame NFκB-mediated chemoresistance, respectively. 20,22,23 Additionally, growth inhibitory and pro-apoptotic effects of silibinin were recently observed in NSCLC A549 and H1299 cells. 19,25 Mechanistically, silibinin modulated cytokines mediated signaling and induced cell cycle two regions of p21 promoter: region a: -324 to -676 and region b: Sp1/Sp3 binding site +41 to -343.…”

Section: Discussionmentioning

confidence: 97%

“…13,20,22,23 Silibinin, a flavonolignan isolated from milk thistle (Silybum marianum) seeds, is well known for its hepatoprotective activity, and is used clinically and as dietary supplement against liver toxicity for decades. 20 Silibinin possesses strong anticancer efficacy against both carcinogen-induced primary lung tumors and chemotherapy resistant lung tumor xenografts, where it decreased tumor incidence, inhibited tumor growth and progression by downregulating inducible nitric oxide synthase and Cox-2 mediated signaling, and overcame NFκB-mediated chemoresistance, respectively.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic modifications and p21-cyclin B1 nexus in anticancer effect of histone deacetylase inhibitors in combination with silibinin on non-small cell lung cancer cells

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Epigenetic modifications and p21-cyclin B1 nexus in anticancer effect of histone deacetylase inhibitors in combination with silibinin on non-small cell lung cancer cells

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…1A). Accumulating evidence indicates that silibinin has anticancer activity in various tumor cells, including cancers of prostate (5)(6)(7)(8)(9), breast (10,11), skin (12), colon (13), lung (14), kidney (15,16), and bladder (17)(18)(19)(20). There is increasing interest in elucidating the mechanisms of action for silibinin as an effective agent for chemoprevention and chemotherapy against various types of cancers.…”

Section: Introductionmentioning

confidence: 99%

Chemopreventive and Chemotherapeutic Effects of Intravesical Silibinin against Bladder Cancer by Acting on Mitochondria

Zeng

Sun

et al. 2011

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Intravesical chemotherapy is often used to prevent the recurrence of superficial bladder cancer after transurethral resection. A search for more effective and less toxic intravesical agents is urgently needed. We previously found the in vitro apoptotic effects of silibinin, a natural flavonoid, on high-risk bladder carcinoma cells. Here, we further explored the underlying mechanisms and examined the intravesical efficacy in the prevention and treatment of bladder cancer. Human bladder carcinoma cell line 5637, which has the same molecular features of high-risk superficial bladder cancer, was used as the model system in vitro and in vivo. Autochthonous rat model of bladder cancer induced by intravesical N-methyl-N-nitrosourea (MNU) was used to investigate its intravesical efficacy. Exposure of 5637 cells to silibinin resulted in growth inhibition and induction of caspase-dependent and -independent apoptosis, which was associated with disruption of mitochondrial membrane potential and selective release of cytochrome c, Omi/HtrA2, and apoptosisinducing factor (AIF) from mitochondria. Silibinin also downregulated survivin and caused nuclear translocation of AIF. Oral silibinin suppressed the growth of 5637 xenografts, which was accompanied with the activation of caspase-3, downregulation of survivin, and increased translocation of AIF. Furthermore, intravesical silibinin effectively inhibited the carcinogenesis and progression of bladder cancer in rats initiated by MNU by reducing the incidence of superficial and invasive bladder lesions without any side effects, which was accompanied with proapoptotic effects. These findings identify the in vitro and in vivo antitumor efficacy of silibinin, and suggest silibinin as an effective and novel intravesical agent for bladder cancer.

show abstract

“…Silymarin possesses hepatoprotective properties and has been widely used for decades to treat patients with liver disease (8). Recent studies have shown that silibinin and silymarin inhibits growth of many cancers including breast, lung, colon, pancreas, and prostate cancer cells (9)(10)(11)(12). The anticancer efficacy of silibinin is associated with cell cycle arrest, apoptosis, and antiangiogenesis (13).…”

Section: Introductionmentioning

confidence: 99%

Combined Treatment with Silibinin and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Overcomes Drug Resistance Caused by T790M Mutation

Rho

Choi

Jeon

et al. 2010

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) produce an initially dramatic response in lung cancer patients harboring a mutation in the EGFR gene, development of acquired resistance is almost inevitable. A secondary mutation of threonine 790 (T790M) is associated with approximately half of the cases of acquired resistance. This study investigated whether the addition of silibinin to therapy with gefitinib or erlotinib could overcome T790M-mediated drug resistance considering that silibinin has various antitumor effects, including EGFR modulation. Silibinin selectively reduced the activity of the EGFR family (EGFR, ErbB2, and ErbB3) through the inhibition of receptor dimerization in lung cancer cells with EGFR mutations, but not in those harboring the wild type. In primary and acquired resistant cells with T790M, addition of silibinin enhanced the ability of EGFR-TKIs to downregulate EGFR signals and to inhibit cell growth. Similarly, the combination of silibinin and erlotinib effectively suppressed tumor growth in erlotinib resistance-bearing PC-9 xenografts. The results indicate that the addition of silibinin to EGFR-TKIs is a promising strategy to overcome T790M-mediated drug resistance. Mol Cancer Ther; 9(12); 3233-43. Ó2010 AACR.

show abstract

Effect of Silibinin on the Growth and Progression of Primary Lung Tumors in Mice

Abstract: Silibinin inhibits lung tumor angiogenesis in an animal model and merits investigation as a chemopreventive agent for suppressing lung cancer progression.

Cited by 151 publications

References 31 publications

Epigenetic modifications and p21-cyclin B1 nexus in anticancer effect of histone deacetylase inhibitors in combination with silibinin on non-small cell lung cancer cells

Epigenetic modifications and p21-cyclin B1 nexus in anticancer effect of histone deacetylase inhibitors in combination with silibinin on non-small cell lung cancer cells

Chemopreventive and Chemotherapeutic Effects of Intravesical Silibinin against Bladder Cancer by Acting on Mitochondria

Combined Treatment with Silibinin and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Overcomes Drug Resistance Caused by T790M Mutation

Contact Info

Product

Resources

About