4.7 Article

Cucurbitacin B induces apoptosis of primary effusion lymphoma via disruption of cytoskeletal organization

期刊

PHYTOMEDICINE
卷 85, 期 -, 页码 -

出版社

ELSEVIER GMBH
DOI: 10.1016/j.phymed.2021.153545

关键词

Actin; AIDS; Cucurbitacin B; PEL; Primary effusion lymphoma

资金

  1. International Collaborative Research Program: The e-ASIA Joint Research Program from the Japan Agency for Medical Research and Development (AMED) [18J00112]
  2. Grants-in-Aid for Scientific Research [18J00112] Funding Source: KAKEN

向作者/读者索取更多资源

The study demonstrated that cucurbitacin B (CuB) can effectively inhibit cell proliferation and induce apoptosis in Primary Effusion Lymphoma (PEL) cells in a dose-dependent manner. CuB also has an impact on cell cycle arrest and affects signaling pathways related to KSHV-derived protein activation. In vivo experiments showed that CuB significantly inhibited solid tumor growth, indicating its potential as a promising agent for PEL treatment.
Background: Primary effusion lymphoma (PEL) is an aggressive B cell non-Hodgkin lymphoma that develops especially in AIDS patients and immunocompromised patients infected with human herpes virus-8 (HHV-8)/ Kaposi's sarcoma-associated herpesvirus (KSHV). PEL has a poor prognosis in patients despite conventional chemotherapeutic treatment, and a safe and efficient therapy is required. Purpose: To examine the effects on PEL of cucurbitacin B (CuB), a triterpene found in plants of the Cucurbitaceae family that has several anti-cancer activities. Study design: We evaluated the anti-cancer activities of CuB in vitro and in vivo. Methods: Cell proliferation of PEL cell lines was measured by MTT assay. Cleaved caspases and signaling transduction associated proteins were analyzed by western blotting. Wright and Giemsa staining and immunofluorescence staining were carried out to observe cell morphology. Cell cycles were analyzed by flow cytometry. RT-PCR was performed to detect viral gene expressions. A xenograft mouse model was employed to evaluate the anti-cancer activity of CuB in vivo. Results: CuB inhibited cell proliferation of PEL cell lines (BCBL-1, BC-1, GTO and TY-1) in a dose-dependent manner (0-50 nM) and induced apoptosis of BCBL-1 cells via caspase activation in a dose- and timedependent manner. In addition, CuB caused cell-shape disruption by inducing actin aggregation and suppressing the p-cofilin level, resulting in BCBL-1 cell arrest at the G2/M phase. In contrast, CuB showed almost no suppression of p-STAT3 and p-Akt activation, which were constitutively activated by KSHV-derived proteins. Furthermore, CuB (0.5 mg/kg) via intraperitoneal injection significantly (p < 0.05) suppressed solid tumor growth in the xenograft mouse model. Conclusion: This study suggests that CuB is a promising agent for PEL treatment.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据