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      Is Open Access

      Thapsigargin induces apoptosis in adrenocortical carcinoma by activating endoplasmic reticulum stress and the JNK signaling pathway: an in vitro and in vivo study

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          Abstract

          Objective

          Thapsigargin (TG) is a natural product that exists in most parts of the plant Thapsia garganica L. and possesses potential anticancer activities against variety tumor cell lines. TG induces endoplasmic reticulum (ER) stress and apoptosis by inhibiting cancer growth. However, the antineoplastic effect of TG in human adrenocortical carcinoma (ACC) cells is still unknown.

          Methods

          In this study, two human ACC cell lines including SW-13 and NCI-H295R were employed to explore the potential role of TG in ACC. A mouse xenograft model of SW-13 cells was established to verify the role of TG in vivo. The cell viability was tested using Cell Counting Kit-8 and Transwell assays. Flow cytometry and Hoechst 33,258 staining were employed to analyze cell apoptosis. RT-qPCR and Western blot (WB) were performed to explore the underlying mechanism of TG-induced apoptosis in ACC cells.

          Results

          The results indicated that TG dose-dependently inhibited proliferation, migration and invasion in human ACC cells. TG significantly increased the mitochondrial rate of apoptosis and ER stress activity in ACC cells and suppressed ACC xenograft growth in vivo. In addition, the expression of Jun N-terminal kinase (JNK) signaling-related genes and proteins was upregulated by the treatment with TG.

          Conclusion

          Our findings suggest that TG inhibits the viability of ACC cells by inducing apoptosis through the activation of JNK signaling. Thus, TG is expected to be a potential candidate for the treatment of ACC.

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          Most cited references 30

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          Adrenocortical carcinoma.

          Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, often with an unfavorable prognosis. Here we summarize the knowledge about diagnosis, epidemiology, pathophysiology, and therapy of ACC. Over recent years, multidisciplinary clinics have formed and the first international treatment trials have been conducted. This review focuses on evidence gained from recent basic science and clinical research and provides perspectives from the experience of a large multidisciplinary clinic dedicated to the care of patients with ACC.
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            Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors.

            Adrenocortical carcinoma (ACC) is a rare tumor with a relatively poor prognosis. The authors' objectives were to examine treatment utilization and factors associated with long-term survival after resection of ACC in a large, national, patient population. Patients diagnosed with ACC from 1985 to 2005 were identified from the National Cancer Data Base (NCDB). Patient, tumor, treatment, and hospital factors associated with survival after resection were examined. For the current study, 3982 patients with ACC were identified. Median age at diagnosis was 55 years. Median tumor size was 13 cm. Of the patients with nodes examined, 26.5% had nodal metastases. Distant metastases were found on presentation in 21.6% of patients. A total of 57.4% of patients underwent surgical resection alone, whereas 16.0% underwent resection with adjuvant chemotherapy or radiation. A total of 19.4% had margin-positive resections. Treatment utilization remained unchanged from 1985 to 2005 (P = .28). Median follow-up was 24 months. Overall 5-year survival for all patients who underwent resection was 38.6% (median survival, 31.9 months). Multivariable analysis demonstrated a higher risk of death with increasing age, poorly differentiated tumors, involved margins, and nodal or distant metastases. Overall survival remained unchanged from 1985 to 2000 (P = .08). ACC carries a poor prognosis for patients commonly presenting with large, locally invasive tumors, involved margins, and metastatic disease. Survival is not affected by size but is diminished with increasing age, poorly differentiated tumors, involved margins, and the presence of regional and distant disease. Identification of novel therapies may help to increase survival, which has remained unchanged over the last 20 years. (c) 2008 American Cancer Society
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              • Record: found
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              • Article: not found

              Adrenal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                12 August 2019
                2019
                : 13
                : 2787-2798
                Affiliations
                [1 ]Department of Integrated Medicine, The Affiliated Tumor Hospital of Guangxi Medical University , Nanning, Guangxi 530021, People’s Republic of China
                [2 ]Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University , Nanning, Guangxi 530021, People’s Republic of China
                Author notes
                Correspondence: Zuojie LuoDepartment of Endocrinology, The First Affiliated Hospital of Guangxi Medical University , 6 Shuangyong Road, Nanning, Guangxi530021, People’s Republic of ChinaTel +86 1 360 786 2298Email Zluo888@163.com
                Article
                209947
                10.2147/DDDT.S209947
                6697672
                © 2019 Wu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 8, Tables: 1, References: 43, Pages: 12
                Categories
                Original Research

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