The inhibitory effect of honokiol, a natural plant product, on vestibular schwannoma cells

Lee, Jong Dae; Lee, Jae Yong; Baek, Byoung Joon; Lee, Byung Don; Koh, Yoon Woo; Lee, Won Sang; Lee, Yu Jin; Kwon, Byoung Mog

doi:10.1002/lary.21781

Cited by 13 publications

(9 citation statements)

References 20 publications

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“…Alternative treatments, based on safe dietary supplements capable of slowing the progression of VS, may represent a more practical approach for many patients. For this reason, we have reported three alternative natural products capable of inhibiting the growth of HEI-193 cells181920. Furthermore, Spear et al .…”

Section: Discussionmentioning

confidence: 98%

Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo

Kim

Fujita

Stanković

et al. 2016

Sci Rep

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Vestibular schwannoma (VS) is an intracranial tumor that causes significant morbidity, including hearing loss, tinnitus, dizziness, and possibly even death from brainstem compression. However, FDA-approved pharmacologic treatments for VS do not exist. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli, with potent chemoprotective effects in several cell types. Our objective was to determine whether SFN is effective against VS in vitro and in vivo. Human primary VS cells, HEI-193 schwannoma cells, and SC4 Nf2−/− Schwann cells were used to investigate the inhibitory effects of SFN in vitro. Cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, and cell viability and metabolic activity was calculated by MTT assay. Apoptosis was measured by flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and Western blot for cleaved caspases. A mouse model with a murine schwannoma allograft was also used to examine the antitumor activity of SFN. SFN exhibited significant antiproliferative activity in schwannoma cells in vitro, via the inhibition of HDAC activity and the activation of ERK. SFN treatment induced apoptosis and cell cycle arrest at the G2/M phase. SFN also significantly inhibited schwannoma growth in vivo. Our preclinical studies motivate a future prospective clinical study of SFN for the treatment of VS.

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Section: Discussionmentioning

confidence: 98%

Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo

Kim

Fujita

Stanković

et al. 2016

Sci Rep

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“…Curcumin found in turmeric, a spice derived from the rhizomes of Curcuma longa of the ginger family, was found to inhibit the growth of HEI-193 cells by down-regulating the phosphorylation of AKT and ERK1/2 20 . Honokiol, a lignan found in Magnolia grandiflora was also shown to exhibit antiproliferative activity in HEI-193 and inhibit ERK phosphorylation 21 . However, none of these compounds has been tested in other NF2-relevant models and their toxicity profiles are largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Extracts from plants in the family Cucurbitaceae have long been used in oriental medicines for their hepatoprotective effects as well as anti-inflammatory and anti-diabetic effects 21 . Importantly, cucurbitacins induce cancer cell death 6 .…”

Section: Discussionmentioning

confidence: 99%

Natural Compounds as Potential Treatments of NF2-Deficient Schwannoma and Meningioma

Spear

Burns

Oblinger

et al. 2013

Otology &Amp; Neurotology

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Hypothesis Cucurbitacin D and goyazensolide, two plant-derived natural compounds, possess potent growth-inhibitory activity in schwannoma and meningioma cells. Background Currently, no FDA-approved drugs are available for neurofibromatosis type 2 (NF2)-associated schwannomas and meningiomas. Selected natural compounds with antineoplastic activity, such as cucurbitacin and goyazensolide, may be developed as potential treatments for these tumors. Methods The Nf2-deficient mouse schwannoma Sch10545 and human benign meningioma Ben-Men-1 cells were treated with various concentrations of cucurbitacin D and goyazensolide. The effect on cell proliferation was determined using resazurin assays. Flow cytometry was used to assess the cell cycle profiles. Western blot analysis was performed to investigate the expression of various signal molecules related to the cell cycle and the AKT pathway. Results Cucurbitacin D inhibited proliferation of Sch10545 cells (IC50 ~0.75 μM) and Ben-Men-1 cells (IC50 ~0.2 μM). Goyazensolide also reduced cell proliferation of Sch10545 cells (IC50 ~0.9 μM) and Ben-Men-1 cells (IC50 ~1 μM). The G2/M population increased in both Sch10545 and Ben-Men-1 cells treated with cucurbitacin D or goyazensolide around the IC50. Cucurbitacin and goyazensolide substantially reduced the levels of cyclins E and A in treated Sch10545 and Ben-Men-1 cells. Cucurbitacin D also inhibited cyclin B, phospho-AKT and phospho-PRAS40 expression. In addition, goyazensolide reduced the levels of phospho-AKT and NFκB and increased the expression of pro-apoptotic Bim in Sch10545 and Ben-Men-1 cells. Conclusions Both cucurbitacin D and goyazensolide effectively inhibit proliferation of NF2-deficient schwannoma and meningioma cells, suggesting that these natural compounds should be further evaluated as potential treatments for NF2-related tumors.

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“…Although it has been used in traditional medicines for thousands of years, a thorough understanding of its bio-activity will aid in applying this compound or its derivatives to human pathologic conditions. It appears to specifically target tumorous cells in the CNS while preserving and protecting healthy neurons and preventing deleterious results from ischemia, seizure, amyloidosis, anxiety, depression, and pain (8, 9, 11, 12, 22, 28, 35, 55, 56). It is possible that many of honokiol’s downstream anti-inflammatory effects could result from modulation at a single upstream site that is yet to be elucidated.…”

Section: Future Directions and Potential Risksmentioning

confidence: 99%

Neuro-Modulating Effects of Honokiol: A Review

Woodbury¹,

Yu²,

Wei³

et al. 2013

Front. Neurol.

113

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Honokiol is a poly-phenolic compound that exerts neuroprotective properties through a variety of mechanisms. It has therapeutic potential in anxiety, pain, cerebrovascular injury, epilepsy, and cognitive disorders including Alzheimer’s disease. It has been traditionally used in medical practices throughout much of Southeast Asia, but has now become more widely studied due to its pleiotropic effects. Most current research regarding this compound has focused on its chemotherapeutic properties. However, it has the potential to be an effective neuroprotective agent as well. This review summarizes what is currently known regarding the mechanisms involved in the neuroprotective and anesthetic effects of this compound and identifies potential areas for further research.

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The inhibitory effect of honokiol, a natural plant product, on vestibular schwannoma cells

Abstract: Honokiol, a low molecular weight natural product, inhibits cell proliferation and promotes apoptosis in schwannoma cells by targeting the ERK pathway. Our data suggest that honokiol can be evaluated as a chemotherapeutic agent for VS.

Cited by 13 publications

References 20 publications

Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo

Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo

Natural Compounds as Potential Treatments of NF2-Deficient Schwannoma and Meningioma

Neuro-Modulating Effects of Honokiol: A Review

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