Hyperforin Suppresses Tumor Growth and NF-ĸB-mediated Anti-apoptotic and Invasive Potential of Non-small Cell Lung Cancer

Chen, Wei Ting; Chen, Ying Kai; Lin, Song; Hsu, Fei‐Ting

doi:10.21873/anticanres.12457

Cited by 8 publications

(10 citation statements)

References 15 publications

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“…Results elucidated that the mRNA level of TRPC6 in psoriasis skin lesions decreased compared with normal people, however, the statistical difference needs further verification (data not show). Hyperforin is also well-known for its anti-inflammatory, anti-tumor, anti-bacterial, antioxidant, and stabilize skin barrier properties (9)(10)(11)(12)(13). Studies had reported the anti-inflammatory effects of hyperforin in pancreatic b cells, microglia, vascular endothelial cells, and neuronal cells (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

“…Remove the dorsal hair of mice (8-10 weeks of age) at a surface area of about 4 to 5 cm 2 as described in our previous publication (13), 5% imiquimod (IMQ) cream (Mingxin Lidi Laboratory, China) was applied daily at a topical dose of 62.5 mg for 7 days to establish IMQ-induced psoriasis mouse model (20).…”

Section: Imq-induced Psoriatic-like Mouse Modelmentioning

confidence: 99%

“…Hyperforin is a major active constituent of Hypericum perforatum L. extract, which has antidepressant, bactericidal, anti-inflammatory, antioxidant, and other effects (9)(10)(11)(12)(13). Clinical studies have supported the topical use of St. John's wort as an effective treatment for psoriasis (14,15), but the specific mechanisms are still not completely explored.…”

Section: Introductionmentioning

confidence: 99%

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Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A–Producing γδ T Cells

Zhang

et al. 2021

Front. Immunol.

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Hyperforin is a major active constituent of Hypericum perforatum L. extract, which is widely used for the treatment of depressive disorders. Recent studies have reported that hyperforin reduced inflammation in stroke and suppressed proliferation and differentiation in keratinocytes. Psoriasis is a chronic immune-mediated inflammatory skin disease in which the IL-23/IL-17 axis plays an important role. To investigate the underlying inflammatory mechanisms and response of hyperforin in psoriasis, we use imiquimod (IMQ)-induced mice model, in vitro cultured murine splenic γδ T cells, and HaCaT cells in this study. Data showed that hyperforin reduced epidermal thickness and decreased IMQ-induced pathological scores of cutaneous skin lesions in mice. Meanwhile we proved that hyperforin suppressed infiltration of CD3+ T cells and downregulated expression of Il1, Il6, Il23, Il17a, Il22, antimicrobial peptides (AMPs) in the skin lesion. Hyperforin significantly inhibited imiquimod-induced splenomegaly, reduced serum levels of TNF-α and IL-6, and IL-17A in splenocytes and draining lymph nodes. Our study also suggested that hyperforin lessened the infiltration of γδ T cell and CCR6+ γδ T cells in spleen and lymph nodes. Hyperforin also suppressed the typical psoriasis-like inflammatory responses and the infiltration of IL-17A+ cells in dermal γδ T cells of IMQ treated Tcrd−/− mice transferred with γδ T cells. In vitro studies, hyperforin reduced the expression and secretion of IL-17A in γδ T cells, and suppressed the activation of MAPK/STAT3 pathways in human keratinocyte HaCaT cells and γδ T cells. In conclusion, hyperforin alleviates IMQ-induced inflammation in psoriasis through suppressing the immune responses exerted by IL-17 A-producing γδ T cells and related cytokines by modulating MAPK/STAT3 pathways. Our study provided a novel therapeutic tragedy for psoriasis by which hyperforin attenuates psoriasis-related inflammatory responses.

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Section: Discussionmentioning

confidence: 99%

Section: Imq-induced Psoriatic-like Mouse Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A–Producing γδ T Cells

Zhang

et al. 2021

Front. Immunol.

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“…Plasmid transfection and stable clone selection protocol were described previously [ 56 , 57 ]. In brief, GBM8401 cells in the plates were added with pGL4.50 luciferase reporter (pGL4.50[luc2/CMV]) plasmid and JetPEI™ transfection reagents mixture overnight.…”

Section: Methodsmentioning

confidence: 99%

Allyl Isothiocyanate (AITC) Induces Apoptotic Cell Death In Vitro and Exhibits Anti-Tumor Activity in a Human Glioblastoma GBM8401/luc2 Model

Chueh

et al. 2022

IJMS

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Some clinically used anti-cancer drugs are obtained from natural products. Allyl isothiocyanate (AITC), a plant-derived compound abundant in cruciferous vegetables, has been shown to possess an anti-cancer ability in human cancer cell lines in vitro, including human brain glioma cells. However, the anti-cancer effects of AITC in human glioblastoma (GBM) cells in vivo have not yet been examined. In the present study, we used GBM8401/luc2 human glioblastoma cells and a GBM8401/luc2-cell-bearing animal model to identify the treatment efficacy of AITC. Here, we confirm that AITC reduced total cell viability and induced cell apoptosis in GBM8401/luc2 cells in vitro. Furthermore, Western blotting also showed that AITC induced apoptotic cell death through decreased the anti-apoptotic protein BCL-2, MCL-1 expression, increased the pro-apoptotic protein BAX expression, and promoted the activities of caspase-3, -8, and -9. Therefore, we further investigated the anti-tumor effects of AITC on human GBM8401/luc2 cell xenograft mice. The human glioblastoma GBM8401/luc2 cancer cells were subcutaneously injected into the right flank of BALB/c nude mice to generate glioblastoma xenograft mice. The animals were randomly divided into three groups: group I was treated without AITC (control); group II with 0.1 mg/day of AITC; and group III with 0.2 mg/day of AITC every 3 days for 27 days. Bodyweight, and tumor volume (size) were recorded every 3 days. Tumors exhibiting Luc2 intensity were measured, and we quantified intensity using Living Image software on days 0, 12, and 24. After treatment, tumor weight from each mouse was recorded. Tumor tissues were examined for histopathological changes using H&E staining, and we analyzed the protein levels via immunohistochemical analysis. Our results indicate that AITC significantly inhibited tumor growth at both doses of AITC due to the reduction in tumor size and weight. H&E histopathology analysis of heart, liver, spleen, and kidney samples revealed that AITC did not significantly induce toxicity. Body weight did not show significant changes in any experiment group. AITC significantly downregulated the protein expression levels of MCL-1, XIAP, MMP-9, and VEGF; however, it increased apoptosis-associated proteins, such as cleaved caspase-3, -8, and -9, in the tumor tissues compared with the control group. Based on these observations, AITC exhibits potent anti-cancer activity in the human glioblastoma cell xenograft model via inhibiting tumor cell proliferation and the induction of cell apoptosis. AITC may be a potential anti-GBM cancer drug that could be used in the future.

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“…Human glioblastoma GBM 8401 cells were cultured in the 10-cm dish with RPMI-1640 supplemented with 10% FBS, 100 U/mL penicillin, and 100 µg/mL streptomycin, in 5% CO 2 humidified incubators at 37 °C [ 34 ]. Plasmid transfection and stable clone selection protocol were described in our previous studies [ 46 , 47 ]. In brief, pGL4.50 luciferase reporter (pGL4.50[ luc2 /CMV]) plasmid and JetPEI™ transfection reagents mixture was added to GBM 8401 cells overnight.…”

Section: Methodsmentioning

confidence: 99%

Bisdemethoxycurcumin Induces Cell Apoptosis and Inhibits Human Brain Glioblastoma GBM 8401/Luc2 Cell Xenograft Tumor in Subcutaneous Nude Mice In Vivo

Hsia

Peng

Chueh

et al. 2022

IJMS

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Bisdemethoxycurcumin (BDMC) has biological activities, including anticancer effects in vitro; however, its anticancer effects in human glioblastoma (GBM) cells have not been examined yet. This study aimed to evaluate the tumor inhibitory effect and molecular mechanism of BDMC on human GBM 8401/luc2 cells in vitro and in vivo. In vitro studies have shown that BDMC significantly reduced cell viability and induced cell apoptosis in GBM 8401/luc2 cells. Furthermore, BDMC induced apoptosis via inhibited Bcl-2 (anti-apoptotic protein) and increased Bax (pro-apoptotic proteins) and cytochrome c release in GBM 8401/luc2 cells in vitro. Then, twelve BALB/c-nude mice were xenografted with human glioblastoma GBM 8401/luc2 cancer cells subcutaneously, and the xenograft nude mice were treated without and with BDMC (30 and 60 mg/kg of BDMC treatment) every 3 days. GBM 8401/luc2 cell xenografts experiment showed that the growth of the tumors was significantly suppressed by BDMC administration at both doses based on the reduction of tumor size and weights. BDMC did not change the body weight and the H&E histopathology analysis of liver samples, indicating that BDMC did not induce systemic toxicity. Meanwhile, treatment with BDMC up-regulated the expressions of BAX and cleaved caspase-3, while it down-regulated the protein expressions of Bcl-2 and XIAP in the tumor tissues compared with the control group. This study has demonstrated that BDMC presents potent anticancer activity on the human glioblastoma GBM 8401/luc2 cell xenograft model by inducing apoptosis and inhibiting tumor cell proliferation and shows the potential for further development to the anti-GBM cancer drug.

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Hyperforin Suppresses Tumor Growth and NF-ĸB-mediated Anti-apoptotic and Invasive Potential of Non-small Cell Lung Cancer

Abstract: These results suggested hyperforin induces apoptosis and inhibits NF-κB-modulated anti-apoptotic and invasive potential in NSCLC.

Cited by 8 publications

References 15 publications

Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A–Producing γδ T Cells

Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A–Producing γδ T Cells

Allyl Isothiocyanate (AITC) Induces Apoptotic Cell Death In Vitro and Exhibits Anti-Tumor Activity in a Human Glioblastoma GBM8401/luc2 Model

Bisdemethoxycurcumin Induces Cell Apoptosis and Inhibits Human Brain Glioblastoma GBM 8401/Luc2 Cell Xenograft Tumor in Subcutaneous Nude Mice In Vivo

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