Synergistic Effects of Arsenic Trioxide and Silibinin on Apoptosis and Invasion in Human Glioblastoma U87MG Cell Line

Zaki‐Dizaji, Majid; Malehmir, Mohsen; Ghavamzadeh, Ardeshir; Alimoghaddam, Kamran; Ghaffari, Seyed H.

doi:10.1007/s11064-011-0620-1

Cited by 50 publications

(30 citation statements)

References 64 publications

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“…Silibinin (Sil), a polyphenolic flavonoid found in milk thistle seeds, has been found to increase TMZ, etoposide and irinotecan toxicity in three different GBM cell lines (i.e., LN229, U87 and A172) [76], and to improve anti-cancer effects of arsenic trioxide in U87 cells by promoting inhibition of cancer cell metabolism and proliferation, and an increase in apoptosis [77]. Nevertheless, to date, there is no clear evidence of a direct effect of either anthocyanins or Sil on GBM and glioma CSCs.…”

Section: Anthocyanins and Silibinin (Sil)mentioning

confidence: 99%

“…Inhibition of GBM cell migration [74] Silibinin (Sil) Increase TMZ, etoposide and irinotecan toxicity in GBM cell lines; improve anti-cancer effects of arsenic trioxide in U87, by promoting inhibition of cancer cell metabolism, proliferation and increase of apoptosis [76,77] Camptothecin (CPT) CPT analogues approved and used in cancer chemotherapy (e.g. (?)…”

Section: Camptothecin (Cpt)-loaded Npsmentioning

confidence: 99%

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Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

et al. 2015

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Glioblastoma multiforme (GBM) are extremely lethal and still poorly treated primary brain tumors, characterized by the presence of highly tumorigenic cancer stem cell (CSC) subpopulations, considered responsible for tumor relapse. In order to successfully eradicate GBM growth and recurrence, new anti-cancer strategies selectively targeting CSCs should be designed. CSCs might be eradicated by targeting some of their cell surface markers and transporters, inducing their differentiation, impacting their hyper-glycolytic metabolism, inhibiting CSC-related signaling pathways and/or by targeting their microenvironmental niche. In this regard, phytocompounds such as curcumin, isothiocyanates, resveratrol and epigallocatechin-3-gallate have been shown to prevent or reverse cancer-related epigenetic dysfunctions, reducing tumorigenesis, preventing metastasis and/or increasing chemotherapy and radiotherapy efficacy. However, the actual bioavailability and metabolic processing of phytocompounds is generally unknown, and the presence of the blood brain barrier often represents a limitation to glioma treatments. Nowadays, nanoparticles (NPs) can be loaded with therapeutic compounds such as phytochemicals, improving their bioavailability and their targeted delivery within the GBM tumor bulk. Moreover, NPs can be designed to increase their tropism and specificity toward CSCs by conjugating their surface with antibodies specific for CSC antigens, with ligands or with glucose analogues. Here we discuss the use of phytochemicals as anti-glioma agents and the applicability of phytochemical-loaded NPs as drug delivery systems to target GBM. Additionally, we provide some examples on how NPs can be specifically formulated to improve CSC targeting.

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Section: Anthocyanins and Silibinin (Sil)mentioning

confidence: 99%

Section: Camptothecin (Cpt)-loaded Npsmentioning

confidence: 99%

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

et al. 2015

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“…Silibinin was found to induce caspase-mediated apoptosis by activating MAPKs as well as reverting sensitivity to TRAIL signaling in otherwise resistant glioma cells by modulating components of the death receptor-mediated apoptotic pathway (73,76). Interestingly, in the glioblastoma cell line, U87MG, silibinin appeared to partially synergize with arsenic trioxide treatments to increase apoptosis while inhibiting cell proliferation, metabolism, and mRNA expression of several proteinases (77) suggesting the possibility of combinatorial treatments to arrest cancer.…”

Section: Broad Spectrum Cancer Chemopreventive Efficacy Of Silibininmentioning

confidence: 99%

Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer

Ting

Deep

Agarwal

2013

AAPS J

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Abstract. Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged deleterious effects on quality of patient life. Prostate cancer chemoprevention is one potential avenue to alleviate these burdens. It is a regime whereby long-term treatments are intended to prevent or arrest cancer development, in contrast to more direct intervention upon disease diagnosis. Based on this intention, cancer chemoprevention generally focuses on the use of nontoxic chemical agents which are well-tolerated for prolonged usage that is necessary to address prostate cancer's multistage and lengthy period of progression. One such nontoxic natural agent is the flavonoid silibinin, derived from the milk thistle plant (Silybum marianum), which has ancient medicinal usage and potent antioxidant activity. Based on these properties, silibinin has been investigated in a host of cancer models where it exhibits broad-spectrum efficacy against cancer progression both in vitro and in vivo without noticeable toxicity. Specifically in prostate cancer models, silibinin has shown the ability to modulate cell signaling, proliferation, apoptosis, epithelial to mesenchymal transition, invasion, metastasis, and angiogenesis, which taken together provides strong support for silibinin as a candidate prostate cancer chemopreventive agent.

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“…Silibinin was reported to decrease migratory and invasive potential and to inhibit vimentin expression and enhance E-cadherin expression in prostate cancer cells (17,39). Recently, silibinin with arsenic was shown to decrease mRNA expression and enzymatic activity of MMP-2 in human glioblastoma cells (40). We observed a strong decrease in migration and matrigel invasion by DU145 cells in silibinin with arsenic treatment that also decreased the expression of MMP-2 and vimentin without any considerable effect on E-cadherin.…”

Section: Discussionmentioning

confidence: 48%

Silibinin Combination with Arsenic Strongly Inhibits Survival and Invasiveness of Human Prostate Carcinoma Cells

Prajapati

Kale

Singh

2015

Nutrition and Cancer

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Effects of silibinin, a naturally occurring flavanone, on prostate carcinoma (PCa) cells in presence of arsenic are not known. Arsenic is clinically approved for leukemia treatment; however, studies are not enough to support its role in the management of solid tumors. In the present study, we observed that silibinin (100 µM) modulated the oxidative status of human PCa DU145 cells exposed to arsenic (0.5 or 5 µM) and inhibited cell growth and survival by primarily inducing autophagy and apoptosis. The silibinin-arsenic combination also inhibited the growth, survival, and clonogenic potential of 22Rv1 PCa cells. Silibinin with 0.5 or 5 µM arsenic induced G1 or G2/M phase arrest, respectively, and decreased the protein levels of CDK2, -4, and -6 and cyclin D1, D3, and E and increased CDK inhibitors p21 and p27. Arsenic alone increased cyclin B1 level and Cdc2 kinase activity which were reduced in silibinin combination. Cell motility and invasiveness along with expression of MMP-2 and vimentin were suppressed. Together, these in vitro findings suggest that in presence of arsenic, silibinin strongly inhibits tumorigenic and metastatic potential of PCa cells.

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Synergistic Effects of Arsenic Trioxide and Silibinin on Apoptosis and Invasion in Human Glioblastoma U87MG Cell Line

Cited by 50 publications

References 64 publications

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer

Silibinin Combination with Arsenic Strongly Inhibits Survival and Invasiveness of Human Prostate Carcinoma Cells

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