Berberine induces mitochondrial‑mediated apoptosis and protective autophagy in human malignant pleural mesothelioma NCI‑H2452 cells

Our plain-English summary of Berberine induces mitochondrial‑mediated apoptosis and protective autophagy in human malignant pleural mesothelioma NCI‑H2452 cells, by Z. Yao, Y. Wan, B. Li, et al (Oncology Reports, 2018).

The study

• Authors: Z. Yao, Y. Wan, B. Li, C. Zhai, F. Yao, Y. Kang, Q. Liu, D. Lin
• Journal: Oncology Reports
• Published: 2018;40(6):3603-3610
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Increasing evidence shows that berberine has antitumor effects against a number of tumor cells. In the present study, we evaluated the effect of berberine on the proliferation of the human malignant pleural mesothelioma (MPM) cell line NCI‑H2452, and explored the therapeutic potential and underlying mechanisms of this agent. Our results showed that berberine inhibited the proliferation of NCI‑H2452 cells in a dose‑ and time‑dependent manner and could induce apoptosis, possibly through a caspase‑9‑dependent intrinsic mitochondrial pathway. In addition, autophagy was induced by berberine, which was characterized by the accumulation of LC3‑II and decreased p62 expression. We used inhibitors of apoptosis and autophagy, and an inducer of autophagy, to evaluate the significance of autophagy in berberine‑induced cell death. The results demonstrated that apoptosis is the primary route through which berberine induces NCI‑H2452 cell death. Berberine‑induced autophagy may be an adaptive response to antitumor agents and have a protective role in MPM cells. Inhibition of autophagy enhanced berberine‑induced apoptosis. Therefore, inhibition of autophagy may be an effective treatment strategy in the management of MPM. In conclusion, berberine is a potent antitumor agent for treating MPM, and it induces mitochondrial‑mediated apoptosis and protective autophagy in human NCI‑H2452 MPM cells.

In plain English

This was a laboratory study of one human malignant pleural mesothelioma cell line, NCI-H2452, grown in culture. No patients or animals were studied, and asbestos itself was not tested. The authors treated the cells with berberine, a plant compound, at 25 to 200 µM. Berberine reduced cell growth more at higher doses and with longer treatment. At 100 µM, the proliferation rate was 87.58%, 46.68% and 33.24% after 24, 48 and 72 hours. After 48 hours at 100 µM, 32.23% of treated cells were apoptotic (undergoing programmed cell death), compared with 3.55% of untreated cells. Protein tests pointed to a mitochondrial, caspase-9 pathway. Berberine also triggered autophagy, a process in which cells break down their own parts. Blocking autophagy with 3-MA increased cell death and apoptosis, while promoting it with rapamycin reduced death. The authors concluded that apoptosis was the main way berberine killed these cells, that autophagy appeared protective, and that inhibiting autophagy may be an effective treatment strategy for this cancer. They noted that they did not measure autophagic flux and that the results need confirming in more cell lines and in in vivo studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment
• Who was studied: The human malignant pleural mesothelioma cell line NCI-H2452, obtained from the Shanghai Institute of Cell Biology, Chinese Academy of Sciences; no human participants
• Exposure: Berberine at 25, 50, 100 or 200 µM, compared with DMSO alone as the control, for 24, 48 and 72 hours. Some experiments also used an autophagy inhibitor (3-MA), an autophagy inducer (rapamycin) and an apoptosis inhibitor (z-VAD-fmk). Asbestos exposure was not studied.
• Main results:
  • In berberine-treated NCI-H2452 cells at 100 µM, the proliferation rate was 87.58±3.72% at 24 hours, 46.68±8.08% at 48 hours and 33.24±7.17% at 72 hours.
  • After 48 hours at 100 µM, the apoptosis rate was 32.23±1.06% in treated cells versus 3.55±0.86% in untreated cells (P<0.001).
  • Berberine treatment released cytochrome c into the cytoplasm and increased the active forms of caspase-9 and caspase-3.
  • Berberine increased conversion of LC3-I to LC3-II (a marker of autophagy), and the increase grew with dose and time.
  • After 48 hours at 200 µM, the death rate of NCI-H2452 cells was 34.66±5.32% (P<0.001).
  • Cell death was higher with the autophagy inhibitor 3-MA plus berberine than with berberine alone, and lower with rapamycin pre-treatment.
  • Cells treated with 3-MA underwent more apoptosis after berberine than cells given berberine alone.
  • The apoptosis inhibitor z-VAD-fmk reduced berberine-induced cell death, and the authors concluded that apoptosis was the main route of cell death.
• The authors' conclusion: The authors concluded that berberine-induced autophagy may be an adaptive, protective response in these mesothelioma cells. They also concluded that inhibiting autophagy enhanced berberine-induced apoptosis and may be an effective treatment strategy for malignant pleural mesothelioma.
• Limitations the authors state:
  • A rise in LC3-II can reflect either the induction of autophagy or the blocked clearance of autophagosomes, so it does not establish autophagy on its own.
  • Autophagic flux, including lysosomal degradation, was not measured in this study.
  • The findings need to be confirmed in more cell lines and in in vivo studies.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Apoptosis, Pleural Mesothelioma.

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