Silibinin inhibits expression of HIF-1α through suppression of protein translation in prostate cancer cells

Jung, Hui-Jung; Park, Jong‐Wook; Lee, Jason S.; Lee, Seong‐Ryong; Jang, Byeong‐Churl; Suh, Seong-Il; Suh, Min-Ho; Baek, Won-Ki

doi:10.1016/j.bbrc.2009.09.068

Cited by 48 publications

(33 citation statements)

References 29 publications

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“…This expression pattern corresponded to an increase in glucose and citrate use along with a concomitant decrease in lactate, cholesterol, and phosphatidylcholine levels in prostatic tumors of silibinin-fed TRAMP mice (128). Silibinin treatment of LNCaP and PC3 prostate cancer cells also inhibited their synthesis of HIF-1α both basally as well as induced by hypoxia (129). …”

Section: Silibinin Exhibits Strong Anti-angiogenic Efficacy Against Pmentioning

confidence: 88%

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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Section: Silibinin Exhibits Strong Anti-angiogenic Efficacy Against Pmentioning

confidence: 88%

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

Ting

Deep

Agarwal

2013

AAPS J

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“…We next investigated whether F2 affected the expression of HIF-1α through the PI3K-AKTmTOR and ERK1/2 pathways, by inhibiting the HIF-1α translational regulators P70S6K and 4E-BP1 (22)(23)(24). As shown in Fig.…”

Section: F2 Inactivates Hypoxia-induced Pi3k-akt-mtor and Mapk-erk1/2mentioning

confidence: 99%

Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro

Zheng

Yang

Hou

et al. 2014

International Journal of Oncology

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Abstract. Overexpression of hypoxia-inducible factor-1 (HIF-1) α, a transcription factor which immortalizes tumors by inducing expression of the genes involved in cell survival, migration and angiogenesis, is closely associated with poor prognosis, increased risk of metastasis and increased mortality. Oligomer procyanidins (F2), a natural fraction from grape seeds, has been demonstrated to have antioxidant and antitumor activities, however the antitumor effect of F2 targeting HIF-1α remains unknown. The present study showed that F2 markedly decreased HIF-1α and the expression of its target genes in cancer cells through inactivating the EGFR-PI3K-AKT-mTOR and MAPK-ERK1/2 pathways. Moreover, F2 suppressed vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 expressions, followed by the inhibition of tumor angiogenesis and cell invasion in a HIF-1α-dependent manner. Collectively, these findings indicate that the antitumor effect of F2 is, at least in part, mediated by suppressing HIF-1α-dependent pathway, and suggest that F2 may be a potentially useful agent for treatment of human cancer.

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“…Genistein, another flavonoid and inhibitor of tyrosine kinases, completely blocks the synthesis of both HIF-1 subunits in human retinal pigment epithelium cells [52] as well as HIF-1 DNA-binding activity [53]. Silibinin, an additional flavonoid isolated from milk thistle (Silybum marianum) inhibits expression of HIF-1a through suppression of protein translation in PC-3 and LNCaP cells [54]. Wondonin reduces the stability of HIF-1a protein and activity in the human keratinocyte cells HaCaT [55].…”

Section: Inhibition Of Hif-a Translationmentioning

confidence: 99%

Modulation of hypoxia-inducible factors (HIF) from an integrative pharmacological perspective

Rodríguez‐Jiménez

Moreno‐Manzano

2011

Cell. Mol. Life Sci.

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Oxygen homeostasis determines the activity and expression of a multitude of cellular proteins and the interplay of pathways that affect crucial cellular processes for development, physiology, and pathophysiology. Hypoxia-inducible factors (HIFs) are transcription factors that respond to changes in available oxygen in the cellular environment and drives cellular adaptation to such conditions. Selective gene expression under hypoxic conditions is the result of an exquisite regulation of HIF, from the pre-transcriptional stage of the HIF gene to the final transcriptional activity of HIF protein. We provide a dissected analysis of HIF modulation with special focus on hypoxic conditions and HIF pharmacological interventions that can guide the application of any future HIF-mediated therapy.

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Silibinin inhibits expression of HIF-1α through suppression of protein translation in prostate cancer cells

Cited by 48 publications

References 29 publications

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

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

Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro

Modulation of hypoxia-inducible factors (HIF) from an integrative pharmacological perspective

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