Ovatodiolide suppresses inflammatory response in BEAS-2B cells by regulating the CREB/AQP5 pathway, and sensitizes nasopharyngeal carcinoma cells to radiation therapy

Liu, Shao‐Cheng; Huang, Chih Ming; Chang, Yung Lung; Bamodu, Oluwaseun Adebayo; Yeh, Chi Tai; Wang, Hsing Won; Lee, Fei Peng; Lin, Chun–Shu

doi:10.1016/j.ejphar.2019.172548

Cited by 11 publications

(8 citation statements)

References 29 publications

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“…Based on previous studies by our team, OV exhibits antibacterial, anti-inflammatory, and anticancer properties [8,9,22]. The present study provides an additional mechanistic insight into the ability of OV to suppress OSCC tumorigenesis by reducing the cargo of CSC-derived EVs.…”

Section: Discussionmentioning

confidence: 58%

“…In addition to the demonstrated ability of OV to inhibit carcinogenesis in different cancer types by our group [8][9][10]22], the present study demonstrated that treatment with OV significantly suppressed the ability of CAL27 (2.91-fold, p < 0.001) and SCC-15 (2.67-fold, p < 0.001) cells to form tumorspheres ( Figure 4A) with concomitant downregulation of PI3K, STAT3, TGFβ1, and β-catenin protein expression levels in OV-treated tumorspheres, compared to their control counterparts ( Figure 4B). Next, our comparative analysis of gene expression profiles of CSC_EVs from control and OV-treated groups showed that CSC_EVs from OV-treated cells contained significantly lower amounts of cargo loads of PI3K, TGF-β1, STAT3, AKT, and miR-21-5p, compared to control CSC_EVs ( Figure 4C).…”

Section: Ov Suppresses Oscc Oncogenicity By Reducing Exosomal Cargosmentioning

confidence: 99%

“…Ovatodiolide (OV) is the bioactive component of the medicinal herb Anisomeles indica (L.) Kuntze (Labiatae) with documented anti-inflammatory properties. Accumulating evidence including from our previous studies indicates that OV elicits anticancer effects by suppressing oncogenic markers such as tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, matrix metalloproteinases (MMPs), and signaling networks such as the Wnt/β-catenin, Hippo/YAP1, and phosphatidylinositol-3 kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways [8][9][10]. Since activation of these signaling networks is characteristic of both cancer cells and stromal cells within the TME, we examined whether OV-mediated anticancer activities could be exploited to disrupt intra-and intercellular communications within the TME.…”

Section: Introductionmentioning

confidence: 99%

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Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Chen

Bamodu

et al. 2019

Cancers

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Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the world. Patients with OSCC often develop treatment resistance, resulting in a poor prognosis. Mounting evidence indicates that interactions between cancerous cells and other components of the tumor microenvironment (TME) determine their response to treatment. Herein, we examined the role of cancer stem cell-derived extracellular vesicles (CSC_EVs) generated from CAL27 and SCC-15 OSCC cells in the development of cisplatin (CDDP) resistance. We demonstrated that CSC_EVs enhance CDDP resistance, clonogenicity, and the tumorsphere formation potential of OSCC cells. Our bioinformatics analyses revealed that OSCC_EVs are enriched with microRNA (miR)-21-5p and are associated with increased metastasis, stemness, chemoresistance, and poor survival in patients with OSCC. Mechanistically, enhanced activity of CSC_EVs was positively correlated with upregulated Cancers 2020, 12, 56 2 of 16 β-catenin, phosphatidylinositol-3 kinase (PI3K), signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and transforming growth factor (TGF)-β1 messenger (m)RNA and protein expression levels. CSC_EVs also conferred a cancer-associated fibroblast (CAF) phenotype on normal gingival fibroblasts (NGFs), with the resultant CAFs enhancing the oncogenicity of OSCC cells. Interestingly, treatment with ovatodiolide (OV), the bioactive component of Anisomeles indica, suppressed OSCC tumorigenesis by reducing the cargo content of EVs derived from CSCs, suppressing self-renewal, and inhibiting the NGF-CAF transformation by disrupting EV-TME interactions. Moreover, by suppressing miR-21-5p, STAT3, and mTOR expressions in CSC_EVs, OV re-sensitized CSCs to CDDP and suppressed OSCC tumorigenesis. In vivo, treatment with OV alone or in combination with CDDP significantly reduced the tumor sphere-forming ability and decreased EV cargos containing mTOR, PI3K, STAT3, β-catenin, and miR-21-5p. In summary, our findings provide further strong evidence of OV's therapeutic effect in OSCC.

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Section: Discussionmentioning

confidence: 58%

Section: Ov Suppresses Oscc Oncogenicity By Reducing Exosomal Cargosmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Chen

Bamodu

et al. 2019

Cancers

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“…Ovatodiolide has been identified as the major bioactive compound responsible for the biological activities of this plant and has been previously isolated and evaluated for anti-cancer activities against several human cancer cell lines [12]. In our previous studies, we found that ovatodiolide sensitizes aggressive human cancer cells to chemotherapy and ameliorates the cancer stemness phenotype and chemotherapy-associated toxicity in an in vitro or/and in vivo models of breast cancer [15], glioblastoma [16], oral squamous cell carcinoma [17,18], colon cancer [19], and nasopha-ryngeal carcinoma [20]. Studies elsewhere have also reported ovatodiolide for significant anti-cancer activities against hepatic cancer stem cells [21], renal [22], and oral [23] cancers.…”

Section: Introductionmentioning

confidence: 96%

Identification of Cancer Hub Gene Signatures Associated with Immune-Suppressive Tumor Microenvironment and Ovatodiolide as a Potential Cancer Immunotherapeutic Agent

Chen

Lawal

et al. 2021

Cancers

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Despite the significant advancement in therapeutic strategies, breast, colorectal, gastric, lung, liver, and prostate cancers remain the most prevalent cancers in terms of incidence and mortality worldwide. The major causes ascribed to these burdens are lack of early diagnosis, high metastatic tendency, and drug resistance. Therefore, exploring reliable early diagnostic and prognostic biomarkers universal to most cancer types is a clinical emergency. Consequently, in the present study, the differentially expressed genes (DEGs) from the publicly available microarray datasets of six cancer types (liver, lung colorectal, gastric, prostate, and breast cancers), termed hub cancers, were analyzed to identify the universal DEGs, termed hub genes. Gene set enrichment analysis (GSEA) and KEGG mapping of the hub genes suggested their crucial involvement in the tumorigenic properties, including distant metastases, treatment failure, and survival prognosis. Notably, our results suggested high frequencies of genetic and epigenetic alterations of the DEGs in association with tumor staging, immune evasion, poor prognosis, and therapy resistance. Translationally, we intended to identify a drug candidate with the potential for targeting the hub genes. Using a molecular docking platform, we estimated that ovatodiolide, a bioactive anti-cancer phytochemical, has high binding affinities to the binding pockets of the hub genes. Collectively, our results suggested that the hub genes were associated with establishing an immune-suppressive tumor microenvironment favorable for disease progression and promising biomarkers for the early diagnosis and prognosis in multiple cancer types and could serve as potential druggable targets for ovatodiolide.

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“…NPC is sensitive to radiotherapy; thus, this treatment strategy has greatly improved local control of lesions and the 5-year survival rate in patients with NPC [5][6][7][8]. However, frequent local recurrence, metastasis, and poor prognosis remain major challenges in the clinical treatment of NPC because the mechanisms related to NPC progression are not completely understood [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-124-3p inhibited progression of nasopharyngeal carcinoma by interaction with PCDH8 and the inactivation of PI3K/AKT/mTOR pathway

Ye¹,

Liao²,

Zeng³

et al. 2021

J. Cancer

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Nasopharyngeal carcinoma (NPC) is characterised by distinct geographical distribution and is particularly prevalent in Asian countries. But the mechanisms related to the progression of nasopharyngeal carcinoma (NPC) are not completely understood. MiR-124-3p functions as a tumor suppressor in many kinds of human cancers. Here, we explored the effects and mechanism of miR-124-3p on the proliferation and colony formation in NPC. In our study, we reported that miR-124-3p was significantly downregulated in NPC tissues and cell lines. Overexpression miR-124-3p decreased NPC cell proliferation and colony formation abilities. Meanwhile, knockdown miR-124-3p increased proliferation and colony formation abilities. Additionally, dual-luciferase assay showed that miR-124-3p could positively regulated PCDH8 by targeting its 3'-UTR. Overexpression of PCDH8 could partially rescue the proliferation and colony formation role of miR-124-3p inhibitor. Our study indicated that miR-124-3p played a tumor suppressor by directly interacting with PCDH8 and inhibiting the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Overall, we found that miR-124-3p inhibited the activation of the PI3K/AKT/mTOR signaling pathway in NPC by interacting with PCDH8. Thus, PCDH8 may be a potential molecular target that impeded NPC proliferation and colony formation.

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Ovatodiolide suppresses inflammatory response in BEAS-2B cells by regulating the CREB/AQP5 pathway, and sensitizes nasopharyngeal carcinoma cells to radiation therapy

Cited by 11 publications

References 29 publications

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Identification of Cancer Hub Gene Signatures Associated with Immune-Suppressive Tumor Microenvironment and Ovatodiolide as a Potential Cancer Immunotherapeutic Agent

MicroRNA-124-3p inhibited progression of nasopharyngeal carcinoma by interaction with PCDH8 and the inactivation of PI3K/AKT/mTOR pathway

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