Molecular mechanism underlying the apoptotic modulation by ethanol extract of Pseudolarix kaempferi in mucoepidermoid carcinoma of the salivary glands

Abstract Background Pseudolarix kaempferi is a traditional Chinese natural product that possesses the potential cytotoxic effects against cancer. However, the precise molecular mechanism underlying its cytotoxic effects has not yet been completely elucidated. Here, we clarify the mechanism via which the ethanol extract of P. kaempferi (EEPK) leads to cytotoxicity mediated by apoptosis in mucoepidermoid carcinoma (MEC) originating from the salivary glands. Methods We investigated the mechanism underlying the anticancer efficacy of EEPK in human MEC in vitro by assessing mitochondrial dysfunction, mRNA levels, and morphological changes in apoptotic cell nuclei as well as by using a cytotoxicity assay, flow cytometric analysis, and western blotting. Results EEPK inhibited the growth of two human MEC cells and stimulated the induction of caspase-mediated apoptosis that was accompanied by mitochondrial membrane depolarization. Compared with the vehicle control groups, EEPK decreased myeloid cell leukemia-1 (Mcl-1) expression in both cells whereas it significantly decreased B cell lymphoma-2 (Bcl-2) expression in MC3 cells only. The EEPK-induced altered Mcl-1 expression was caused by translational inhibition and proteasomal degradation. Additionally, EEPK significantly increased p-Bcl-2 (Ser70) expression regardless of its total forms by facilitating the activation of the c-Jun N-terminal kinase (JNK) signaling pathway, which exhibited cell context dependency. Nevertheless, JNK activation following EEPK treatment was, at least in part, required for the proapoptotic efficacy of EEPK in both cells. Conclusions This study revealed that EEPK-induced alterations of Mcl-1 inhibition and JNK/Bcl-2 phosphorylation cause apoptosis and provided basic preclinical data for future clinical trials regarding therapy for patients with MEC. Graphic abstract

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Uncovering the Molecular Mechanism of Anti-Allergic Activity of Silkworm Pupa-Grown Cordyceps militaris Fruit Body

The American Journal of Chinese Medicine ◽

10.1142/s0192415x17500306 ◽

2017 ◽

Vol 45 (03) ◽

pp. 497-513 ◽

Cited By ~ 5

Author(s):

Ting-Feng Wu ◽

Yu-Yi Chan ◽

Wan-Yin Shi ◽

Meng-Ting Jhong

Keyword(s):

Mast Cells ◽

Molecular Mechanism ◽

De Novo ◽

Fruit Body ◽

Ethanol Extract ◽

Cordyceps Militaris ◽

Lipid Mediators ◽

Interleukin 4 ◽

Mrna Levels ◽

Silkworm Pupa

Cordyceps militaris has been widely used as an herbal drug and tonic food in East Asia and has also been recently studied in the West because of its various pharmacological activities such as antitumoral, anti-inflammatory and immunomodulatory effects. In this study, we examined the molecular mechanism underlying the anti-allergic activity of ethanol extract prepared from silkworm pupa-cultivated Cordyceps militaris fruit bodies in activated mast cells. Our results showed that ethanol extract treatment significantly inhibited the release of [Formula: see text]-hexosaminidase (a degranulation marker) and mRNA levels of tumor necrosis factor-[Formula: see text] as well as interleukin-4 in RBL-2H3 cells. The cells were sensitized with 2,4-dinitrophenol specific IgE and then stimulated with human serum albumin conjugated with 2,4-dinitrophenol. Oral administration of 300[Formula: see text]mg/kg ethanol extract significantly ameliorated IgE-induced allergic reaction in mice with passive cutaneous anaphylaxis. Western immunoblotting results demonstrated that ethanol extract incubation significantly inhibited Syk/PI3K/MEKK4/JNK/c-jun biochemical cascade in activated RBL-2H3 cells, which activated the expression of various allergic cytokines. In addition, it suppressed Erk activation and PLC[Formula: see text] evocation, which would respectively evoke the synthesis of lipid mediators and Ca[Formula: see text] mobilization to induce degranulation in stimulated RBL-2H3 cells. A compound, identified as [Formula: see text]-sitostenone, was shown to inhibit [Formula: see text]–hexosaminidase secretion from activated mast cells. Our study demonstrated that ethanol extract contained the ingredients, which could inhibit immediate degranulation and de novo synthesis of allergic lipid mediators and cytokines in activated mast cells.

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Sclerosing mucoepidermoid carcinoma of the salivary glands: report of three cases with special concern to the counterpart accompanied by eosinophilia

Medical Molecular Morphology ◽

10.1007/s00795-021-00285-7 ◽

2021 ◽

Author(s):

Hiroshi Harada ◽

Yasuo Toyozumi ◽

Takakazu Sasaguri ◽

Kayo Kuyama ◽

Shin-ichi Nakatsuka ◽

...

Keyword(s):

Salivary Glands ◽

Mucoepidermoid Carcinoma ◽

Special Concern ◽

Sclerosing Mucoepidermoid Carcinoma

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Anthracycline-induced cytotoxicity in the GL261 glioma model system

Molecular Biology Reports ◽

10.1007/s11033-020-06109-8 ◽

2021 ◽

Author(s):

Amber M. Tavener ◽

Megan C. Phelps ◽

Richard L. Daniels

Keyword(s):

Cell Viability ◽

Tumor Cells ◽

Flow Cytometric Analysis ◽

Annexin V ◽

Chemotherapeutic Agents ◽

Cytotoxic Effects ◽

High Concentrations ◽

Induced Apoptosis ◽

Dose Dependent ◽

Gl261 Glioma

AbstractGlioblastoma (GBM) is a lethal astrocyte-derived tumor that is currently treated with a multi-modal approach of surgical resection, radiotherapy, and temozolomide-based chemotherapy. Alternatives to current therapies are urgently needed as its prognosis remains poor. Anthracyclines are a class of compounds that show great potential as GBM chemotherapeutic agents and are widely used to treat solid tumors outside the central nervous system. Here we investigate the cytotoxic effects of doxorubicin and other anthracyclines on GL261 glioma tumor cells in anticipation of novel anthracycline-based CNS therapies. Three methods were used to quantify dose-dependent effects of anthracyclines on adherent GL261 tumor cells, a murine cell-based model of GBM. MTT assays quantified anthracycline effects on cell viability, comet assays examined doxorubicin genotoxicity, and flow cytometry with Annexin V/PI staining characterized doxorubicin-induced apoptosis and necrosis. Dose-dependent reductions in GL261 cell viability were found in cells treated with doxorubicin (EC50 = 4.9 μM), epirubicin (EC50 = 5.9 μM), and idarubicin (EC50 = 4.4 μM). Comet assays showed DNA damage following doxorubicin treatments, peaking at concentrations of 1.0 μM and declining after 25 μM. Lastly, flow cytometric analysis of doxorubicin-treated cells showed dose-dependent induction of apoptosis (EC50 = 5.2 μM). Together, these results characterized the cytotoxic effects of anthracyclines on GL261 glioma cells. We found dose-dependent apoptotic induction; however at high concentrations we find that cell death is likely necrotic. Our results support the continued exploration of anthracyclines as compounds with significant potential for improved GBM treatments.

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A Chalcone from Ashitaba (Angelica keiskei) Stimulates Myoblast Differentiation and Inhibits Dexamethasone-Induced Muscle Atrophy

Nutrients ◽

10.3390/nu11102419 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2419 ◽

Cited By ~ 5

Author(s):

Minson Kweon ◽

Hyejin Lee ◽

Cheol Park ◽

Yung Hyun Choi ◽

Jae-Ha Ryu

Keyword(s):

Muscle Atrophy ◽

Muscle Protein ◽

Ethanol Extract ◽

Mitogen Activated Protein Kinase ◽

Myoblast Differentiation ◽

Active Principle ◽

Mrna Levels ◽

C2c12 Myoblasts ◽

E3 Ligases ◽

Angelica Keiskei

Ashitaba, Angelica keiskei Koidzumi (AK), as a traditional medicine in Korea, Japan, and China, has been known as an elixir of life having therapeutic potential. However, there is no scientific evidence to support that Ashitaba can enhance or maintain muscle strength. To find a new therapeutic agent from the medicinal plant, we evaluated the anti-myopathy effect of chalcones from ethanol extract of AK (EAK) in cellular and animal models of muscle atrophy. To examine anti-myopathy activity, EAK was treated into dexamethasone injected rats and muscle thickness and histopathological images were analyzed. Oral administration of EAK (250 or 500 mg/kg) alleviated muscle atrophic damages and down-regulated the mRNA levels of muscle-specific ubiquitin-E3 ligases. Among ten compounds isolated from EAK, 4-hydroxyderricin was the most effective principle in stimulating myogenesis of C2C12 myoblasts via activation of p38 mitogen-activated protein kinase (MAPK). In three cellular muscle atrophy models with C2C12 myoblasts damaged by dexamethasone or cancer cell-conditioned medium, 4-hydroxyderricin protected the myosin heavy chain (MHC) degradation through suppressing expressions of MAFbx, MuRF-1 and myostatin. These results suggest that the ethanol extract and its active principle, 4-hydroxyderricin from AK, can overcome the muscle atrophy through double mechanisms of decreasing muscle protein degradation and activating myoblast differentiation.

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Kallikrein-related peptidase 10 expression in salivary gland tissues and tumours

The International Journal of Biological Markers ◽

10.5301/jbm.2012.10373 ◽

2012 ◽

Vol 27 (4) ◽

pp. 381-388 ◽

Cited By ~ 5

Author(s):

Mark R. Darling ◽

Nelly N. Hashem ◽

Irene Zhang ◽

Mohamed Mohamed ◽

Kevin Fung ◽

...

Keyword(s):

Salivary Gland ◽

Adenoid Cystic Carcinoma ◽

Salivary Glands ◽

Pleomorphic Adenoma ◽

Mucoepidermoid Carcinoma ◽

Salivary Gland Tumour ◽

Immunoperoxidase Staining ◽

Aberrant Expression ◽

Adenoid Cystic ◽

Gland Tumour

Objectives Kallikrein-related peptidase 10 (KLK10) has been implicated in the development of several types of cancer. The purpose of this study was to analyze the expression of KLK10 in 3 types of salivary gland tumour and normal salivary glands. Materials and methods: A standard immunoperoxidase staining technique was used to assess the Immunoexpression profile of KLK10 in normal salivary glands and 3 types of salivary gland tumour: pleomorphic adenoma, adenoid cystic carcinoma and mucoepidermoid carcinoma. Results Pleomorphic adenomas showed significantly lower KLK10 levels than control tissues. Neither of the malignant tumours (adenoid cystic carcinoma and mucoepidermoid carcinoma) showed a significant alteration in the immunoreactive scores of KLK10 in comparison with the normal salivary gland tissues. KLK10 immunoreactive scores were comparable in adenoid cystic carcinoma and mucoepidermoid carcinoma. Pleomorphic adenoma had significantly lower levels of KLK10 than mucoepidermoid carcinoma. Conclusions The finding of lower KLK10 levels in pleomorphic adenoma suggests aberrant expression in a tumour that develops primarily from myoepithelial cells. A kallikrein cascade may play a role in the development and/or outcome of some salivary gland tumours.

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The oncofetal protein IMP3 is an indicator of early recurrence and poor outcome in mucoepidermoid carcinoma of salivary glands

Cancer Biology and Medicine ◽

10.20892/j.issn.2095-3941.2016.0037 ◽

2016 ◽

Vol 13 (2) ◽

pp. 286-295

Author(s):

Mohamed R. Elshafey ◽

Rehab A. Ahmed ◽

Mohamed I Mourad ◽

Essam T. Gaballah ◽

...

Keyword(s):

Salivary Glands ◽

Mucoepidermoid Carcinoma ◽

Early Recurrence ◽

Poor Outcome

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Mucoepidermoid Carcinoma of Palatal Minor Salivary Glands with Intracranial Extension: A Case Report and Literature Review

Journal of Neurological Surgery Reports ◽

10.1055/s-0036-1593396 ◽

2016 ◽

Vol 77 (04) ◽

pp. e156-e159 ◽

Cited By ~ 2

Author(s):

Rimal Dossani ◽

Hesam Akbarian-Tefaghi ◽

Lori Lemonnier ◽

Vikas Mehta ◽

Jamie Jacobsohn ◽

...

Keyword(s):

Case Report ◽

Literature Review ◽

Salivary Glands ◽

Mucoepidermoid Carcinoma ◽

Intracranial Extension ◽

Minor Salivary Glands

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t(6;22)(p21;q12) in mucoepidermoid carcinoma of the salivary glands

Atlas of Genetics and Cytogenetics in Oncology and Haematology ◽

10.4267/2042/44903 ◽

2011 ◽

Author(s):

JL Huret

Keyword(s):

Salivary Glands ◽

Mucoepidermoid Carcinoma

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Potential Metabolite Nymphayol Isolated from Water Lily (Nymphaea stellata) Flower Inhibits MCF-7 Human Breast Cancer Cell Growth via Upregulation of Cdkn2a, pRb2, p53 and Downregulation of PCNA mRNA Expressions

Metabolites ◽

10.3390/metabo10070280 ◽

2020 ◽

Vol 10 (7) ◽

pp. 280

Author(s):

Laila Naif Al-Harbi ◽

Pandurangan Subash-Babu ◽

Manal Abdulaziz Binobead ◽

Maha Hussain Alhussain ◽

Sahar Abdulaziz AlSedairy ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Cell Viability ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Kinase Inhibitor ◽

B Cell Lymphoma ◽

Nuclear Antigen ◽

Mrna Levels ◽

Mcf 7

Controlled production of cyclin dependent kinases (CDK) and stabilization of tumor suppressor genes are the most important factors involved in preventing carcinogenesis. The present study aimed to explore the cyclin dependent apoptotic effect of nymphayol on breast cancer MCF-7 cells. In our previous study, we isolated the crystal from a chloroform extract of Nymphaea stellata flower petals and it was confirmed as nymphayol (17-(hexan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-ol) using x-ray diffraction (XRD), Fourier transform infrared (FTIR), and mass spectroscopy (MS) methods. The cytotoxic effect of nymphayol on MCF-7 cells were analyzed using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The cellular and nuclear damage was determined using propidium iodide (PI) and acridine orange/ethidium bromide (AO/ErBr) staining. Tumor suppressor and apoptosis related mRNA transcript levels were determined using real-time polymerase chain reaction (RT-PCR). Nymphayol potentially inhibits MCF-7 cell viability up to 78%, and the IC50 value was observed as 2.8 µM in 24 h and 1.4 µM in 48 h. Treatment with nymphayol significantly increased reactive oxygen species (ROS) level and the tunnel assay confirmed DNA damage. We found characteristically 76% apoptotic cells and 9% necrotic cells in PI and AO/ErBr staining after 48 h treatment with 2.8 µM of nymphayol. Gene expression analysis confirmed significantly (p ≤ 0.001) increased mRNA levels of cyclin dependent kinase inhibitor 2A (Cdkn2a), retinoblastoma protein 2 (pRb2), p53, nuclear factor erythroid 2-factor 2 (Nrf2), caspase-3, and decreased B-cell lymphoma 2 (Bcl-2), murine double minute 2 (mdm2), and proliferating cell nuclear antigen (PCNA) expression after 48 h. Nymphayol effectively inhibited breast cancer cell viability, and is associated with early expression of Cdkn2a, pRb2, and activation of p53 and caspases.

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