Honokiol inhibits hypoxia-inducible factor-1 pathway

Lan, Keng Li; Lan, Keng‐Li; Sheu, Meei-Ling; Chen, Ming Yuan; Shih, Yi Sheng; Hsu, Fu-Chuan; Wang, Hong Ming; Liu, Ru‐Shi; Yen, Sang Hue

doi:10.3109/09553002.2011.568572

Cited by 27 publications

(17 citation statements)

References 36 publications

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“…Hypoxic tumors tend to be more aggressive, more likely to metastasize, more resistant to conventional therapies, and are associated with a poor prognosis [4]–[6]. The gene encoding HIF1 (hypoxia-inducible factor-1), which is composed of the HIF1α and HIF1β subunits, is perhaps the most studied gene that plays an essential role in the response to hypoxia [7]. HIF1α is stable under hypoxic conditions, with its expression rapidly decreasing under normoxic conditions, whereas HIF1β is constitutively expressed under both conditions [8].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Inducible MiR-210 Is an Independent Prognostic Factor and Contributes to Metastasis in Colorectal Cancer

Yang

et al. 2014

PLoS ONE

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MicroRNA-210 (miR-210), the master hypoxamir, plays pleiotropic roles in certain cancers; however, its role in the development of human colorectal cancer remains unclear. Herein, we report that miR-210 is frequently up-regulated in colorectal cancer tissues, with high miR-210 expression significantly correlating with large tumor size, lymph node metastasis, advanced clinical stage and poor prognosis. Functionally, miR-210 overexpression promotes the migration and invasion of colorectal cancer cells. Furthermore, miR-210 can be induced by hypoxia and mediates the hypoxia-induced metastasis of colorectal cancer cells. In addition, vacuole membrane protein 1 (VMP1) is identified as the direct and functional target of miR-210. Thus, miR-210 is a useful biomarker for hypoxic tumor cells and a prognostic factor that plays an essential role in colorectal cancer metastasis.

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Section: Introductionmentioning

confidence: 99%

Hypoxia-Inducible MiR-210 Is an Independent Prognostic Factor and Contributes to Metastasis in Colorectal Cancer

Yang

et al. 2014

PLoS ONE

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“…It has recently been reported that Honokiol obtained from Magnolia grandifloris and used for thousands of years in traditional Asian medicine modulates HIF at different levels. Honokiol regulates the HIF-1a protein accumulation as well as its transcriptional activity in subcutaneous murine colon carcinoma [98].…”

Section: Modulation Of Hif Post-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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“…Adaptation of tumor cells to the hypoxic conditions depends on the hypoxia-inducible factor 1 (HIF-1), a transcriptional activator of cell survival, proliferation, angiogenesis, invasion and metastasis genes [6,7]. Recently, it has been demonstrated that a specific set of microRNAs (miRNAs) molecules are upregulated by hypoxia [8].…”

Section: Introductionmentioning

confidence: 99%

Effects of knockdown of miR-210 in combination with ionizing radiation on human hepatoma xenograft in nude mice

et al. 2013

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BackgroundSolid tumors usually develop local hypoxia, which renders them resilient to radiotherapy. MiR-210 is the most consistently and robustly induced miRNA under hypoxia and functions as a micro-controller of a wide range of cellular responses to hypoxia. Hence, it is important to investigate the effect of knockdown of miR-210 in tumorigenesis and evaluate the efficacy of knockdown of miR-210 in combination with radiotherapy on human tumor xenograft in nude mice.Materials and methodsSMMC-7721 Cells with stable integration of the anti-sense miR-210 were generated through lentiviral-mediated gene transfer and were subcutaneously implanted into nude mice. Mice were monitored for tumor growth and survival after radiotherapy. MiR-210 expression in tumor tissues was assessed by real-time Reverse transcription-Polymerase Chain Reaction (RT-PCR). Protein expression of HIF-1α and miR-210 targeted genes in human hepatoma xenograft was assessed by Western blot. Tumors were analyzed for proliferation, apoptosis, and angiogenesis biomarkers by immunohistochemistry staining.ResultsTumor growth was delayed in miR-210 downregulated xenograft. Knockdown of miR-210 increased protein expression of miR-210 targeted genes, but decreased HIF-1α protein in hepatoma xenograft. Knockdown of miR-210 in combination with radiotherapy is more effective than radiotherapy alone or miR-210 knockdown therapy alone in suppressing tumor growth and extending survival duration. Combined therapy decreased Ki-67-positive cells and CD31-positive cells and increased TUNEL-positive cells in tumor xenograft.ConclusionsKnockdown of miR-210 in combination with radiotherapy showed an enhanced anti-tumor effect on human hepatoma xenograft. Our experiments demonstrated specific inhibition of miR-210 expression might be a means to enhance the effectiveness of radiotherapy to human hepatoma.

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Honokiol inhibits hypoxia-inducible factor-1 pathway

Abstract: Our data suggest that honokiol can exert its anticancer activity as a HIF-1α inhibitor by reducing HIF-1α protein level and suppressing the hypoxia-related signaling pathway. The animal experiment indicates that honokiol improves the therapeutic efficacy of radiation.

Cited by 27 publications

References 36 publications

Hypoxia-Inducible MiR-210 Is an Independent Prognostic Factor and Contributes to Metastasis in Colorectal Cancer

Hypoxia-Inducible MiR-210 Is an Independent Prognostic Factor and Contributes to Metastasis in Colorectal Cancer

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

Effects of knockdown of miR-210 in combination with ionizing radiation on human hepatoma xenograft in nude mice

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