Baicalin Regulates Proliferation, Apoptosis, Migration, and Invasion in Mesothelioma

Our plain-English summary of Baicalin Regulates Proliferation, Apoptosis, Migration, and Invasion in Mesothelioma, by W.F. Xu, F. Liu, Y.C. Ma, et al (Medical Science Monitor, 2019).

The study

• Authors: W.F. Xu, F. Liu, Y.C. Ma, Z.R. Qian, L. Shi, H. Mu, F. Ding, X.Q. Fu, X.H. Li
• Journal: Medical Science Monitor
• Published: 2019;25:8172-8180
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

BACKGROUND Baicalin, one of the main bioactive components extracted from the traditional Chinese medicine baical Skullcap root, has an anti-tumor activity which had been studied in several cancers. However, its role in human mesothelioma remains unknown. In this study, we investigated the anti-tumor mechanisms of baicalin in the mesothelioma cell line MESO924. MATERIAL AND METHODS Effects of baicalin on mesothelioma were assessed by measuring cell viability, apoptosis, migration, invasion, inactivation of signaling intermediates, and cell-cycle alterations. RESULTS Baicalin inhibited the proliferation, migration, and invasion of human mesothelioma cells and increased their apoptosis, all in a dose-dependent manner. Specifically, baicalin decreased the expression of p-EGFR, p-AKT, p-MAPK, p-S6, Bcl-2, and VEGF and increased the expression of Bax in mesothelioma cells. The suppressed mesothelioma cellular proliferation is due to the arrest of the S cell cycle by baicalin. Inhibition of the PI3K/AKT/mTOR signaling pathway by a PI3K/AKT/mTOR inhibitor augmented the anti-proliferation effects induced by baicalin. In addition, baicalin increased the sensitivity of MESO924 to the chemotherapeutic drugs doxorubicin, cisplatin, and pemetrexed. CONCLUSIONS These results highlight the roles of baicalin in inhibiting cell growth, migration, and invasion of mesothelioma cells while increasing apoptosis and sensitizing cells to chemotherapeutic agents through the PI3K/AKT/mTOR signaling pathway, which indicates that baicalin could be a useful drug for mesothelioma therapy.

In plain English

This was a laboratory study of one human mesothelioma cell line, MESO924, grown in dishes. It did not involve patients and did not study asbestos exposure. The cells had been established from epithelial-type mesotheliomas. The authors treated the cells for 48 hours with baicalin, a compound from Skullcap root used in traditional Chinese medicine, mainly at 50 and 100 μM. Baicalin lowered cell viability in a dose-dependent manner. It also raised the share of cells held in the S phase of the cell cycle, from 10.81% in control cells to 32.85% at 100 μM. Dying (apoptotic) cells rose from 3.8% in controls to 8.5% at 100 μM. Baicalin reduced cell movement and invasion and lowered the activated forms of several growth-signal proteins. Adding baicalin to the chemotherapy drugs doxorubicin, cisplatin or pemetrexed reduced viability more than each drug alone. The authors concluded that baicalin might be a useful drug for treating mesothelioma. They noted that they tested only one cell line, examined only a few genes, and did not know whether other signaling pathways were involved.

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) study in a cultured human mesothelioma cell line
• Who was studied: A single human mesothelioma cell line, MESO924, established from epithelial-type mesotheliomas taken at surgery from previously untreated patients. The article does not say whether these were pleural or peritoneal tumors.
• Exposure: No asbestos exposure was studied. The cells were treated with baicalin, mainly at 50 and 100 μM for 48 hours (viability was also tested at 10 to 200 μM). Some cells were also given the PI3K/AKT/mTOR inhibitor LY294002 (10 μM) or chemotherapy drugs: doxorubicin (2.5 μM), cisplatin (5 μM) or pemetrexed (0.1 μM).
• Main results:
  • Compared with control (DMSO-treated) MESO924 cells, baicalin decreased cell viability in a dose-dependent manner.
  • The share of MESO924 cells in the G1 phase of the cell cycle was 80.63% in controls, 64.94% with 50 μM baicalin and 57.01% with 100 μM baicalin.
  • The share of MESO924 cells in the S phase was 10.81% in controls, 24.89% with 50 μM baicalin and 32.85% with 100 μM baicalin.
  • Apoptotic MESO924 cells measured by flow cytometry were 3.8% in controls, 5.2% with 50 μM baicalin and 8.5% with 100 μM baicalin.
  • Baicalin at 50 and 100 μM significantly increased caspase 3/7 activity, a marker of apoptosis, in MESO924 cells.
  • In the wound-healing assay, baicalin suppressed the closing of a scratch made in the MESO924 cell layer at 48 hours. No numbers were given.
  • In chamber assays, baicalin inhibited invasion of MESO924 cells more than in the control group. No numbers were given.
  • After 6 hours, baicalin had little effect on total EGFR, AKT, MAPK and S6 proteins, but lowered their activated (phosphorylated) forms in a dose-dependent manner.
  • LY294002 alone (10 μM) reduced MESO924 cell viability by about 25% at day 2. Baicalin plus LY294002 inhibited proliferation more than either treatment alone.
  • Used alone for 48 hours, doxorubicin reduced MESO924 proliferation by about 40%, cisplatin by about 30% and pemetrexed by about 25%.
  • Combined with baicalin, viability fell by about 60 to 80% with doxorubicin, about 50 to 75% with cisplatin, and about 53 to 82% with pemetrexed.
  • After 48 hours of baicalin, Bcl-2 mRNA fell by about 25 to 60% and Bax mRNA rose about 1.4 to 2-fold in MESO924 cells, in a dose-dependent manner.
  • Baicalin lowered VEGF mRNA in MESO924 cells by about 34 to 70%, in a dose-dependent manner.
• The authors' conclusion: The authors concluded that baicalin might be a useful drug for the treatment of mesothelioma.
• Limitations the authors state:
  • The study looked only at Bcl-2, Bax and VEGF; other effects of baicalin were not studied.
  • It is unclear whether signaling pathways other than PI3K/AKT/mTOR were involved.
  • Only one mesothelioma cell line was tested, and other cell lines might respond differently.
  • Other inhibitors of the PI3K/AKT/mTOR pathway were not assessed.

Topics

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

Medical terms in this study, explained in our Lexicon: Apoptosis, Mesothelioma, EGFR, Doxorubicin, Cisplatin, Pemetrexed (Alimta).

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