Open Access

Codonopis bulleynana Forest ex Diels inhibits autophagy and induces apoptosis of colon cancer cells by activating the NF-κB signaling pathway

  • Authors:
    • Yunpeng Luan
    • Yanmei Li
    • Lina Zhu
    • Shuangqing Zheng
    • Dechang Mao
    • Zhuxue Chen
    • Yong Cao
  • View Affiliations

  • Published online on: December 21, 2017     https://doi.org/10.3892/ijmm.2017.3337
  • Pages: 1305-1314
  • Copyright: © Luan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Despite its favorable clinical efficacy, oxaliplatin‑based chemotherapy frequently results in treatment withdrawal and induces liver damage in colon cancer. Therefore, it is important to develop novel drugs, which can safely and effectively complement or replace the therapeutic effects of oxaliplatin. Codonopis bulleynana Forest ex Diels (cbFeD) has wide range of pharmacological effects, including anticancer effects. In the present study, the anticancer activity of cbFeD and its potential molecular mechanisms were investigated. In vitro, cell counting kit‑8 assays and flow cytometry were used to assess the anti‑proliferation and apoptosis‑promoting activities of cbFeD. Transmission electron microscopy was used to monitor the autophagic vesicles. Immunofluorescence staining was performed to observe the nuclear translocation of p65 and the fluorescence of microtubule‑associated protein 1 light chain 3 (LC3) B‑II. The protein expression levels of p65, inhibitor of nuclear factor (NF)‑κB (IκB) a, LC3B‑I, LC3B‑II and Beclin‑1 were detected using western blot analysis. In vivo, the antitumor effect of cbFeD was assessed in colon cancer‑bearing nude mice as a model. H&E staining and immunohistochemistry (IHC) were performed, with oxaliplatin set as a positive control. The results showed that cbFeD inhibited cell proliferation and promoted cell apoptosis in a dose‑dependent manner. The effects of a high dose of cbFeD on colon cancer cells were similar to those of oxaliplatin. In HCT116 and SW480 cells, cbFeD inhibited the expression of IκBα, LC3B‑I/II and Beclin‑1, and the results of western blot analysis and immunofluorescence showed that, in the cells treated with cbFeD, p65 gradually entered nuclei in a dose‑dependent manner, and the expression of LC3B‑II was gradually reduced. The results of the acridine orangestaining and electron microscopy demonstrated fewer autophagic vesicles in the high‑dose cbFeD group and the oxaliplatin group. The high dose of cbFeD reversed the effect of pyrrolidine dithiocarbamate, a p65‑inhibitor, on the expression of p65, LC3B‑I, LC3B‑II and Beclin‑1, and on the production of autophagic vacuoles. The high dose of cbFeD and oxaliplatin also suppressed tumorigenicity in vivo. The results of the H&E and IHC staining confirmed the inhibition of autophagy (LC3 and Beclin‑1) and activation of p65 by treatment with the high dose of cbFeD and oxaliplatin. Taken together, cbFeD exhibited an antitumor effect in colon cancer cells by inhibiting autophagy through activation of the NF‑κB pathway. Therefore, cbFeD may be a promising Chinese herbal compound for development for use in cancer therapy.
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March 2018
Volume 41 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Luan, Y., Li, Y., Zhu, L., Zheng, S., Mao, D., Chen, Z., & Cao, Y. (2018). Codonopis bulleynana Forest ex Diels inhibits autophagy and induces apoptosis of colon cancer cells by activating the NF-κB signaling pathway. International Journal of Molecular Medicine, 41, 1305-1314. https://doi.org/10.3892/ijmm.2017.3337
MLA
Luan, Y., Li, Y., Zhu, L., Zheng, S., Mao, D., Chen, Z., Cao, Y."Codonopis bulleynana Forest ex Diels inhibits autophagy and induces apoptosis of colon cancer cells by activating the NF-κB signaling pathway". International Journal of Molecular Medicine 41.3 (2018): 1305-1314.
Chicago
Luan, Y., Li, Y., Zhu, L., Zheng, S., Mao, D., Chen, Z., Cao, Y."Codonopis bulleynana Forest ex Diels inhibits autophagy and induces apoptosis of colon cancer cells by activating the NF-κB signaling pathway". International Journal of Molecular Medicine 41, no. 3 (2018): 1305-1314. https://doi.org/10.3892/ijmm.2017.3337