Sialic acid-binding lectin (leczyme) induces apoptosis to malignant mesothelioma and exerts synergistic antitumor effects with TRAIL

Our plain-English summary of Sialic acid-binding lectin (leczyme) induces apoptosis to malignant mesothelioma and exerts synergistic antitumor effects with TRAIL, by T. Tatsuta, M. Hosono, K. Takahashi, et al (International Journal of Oncology, 2014).

The study

• Authors: T. Tatsuta, M. Hosono, K. Takahashi, T. Omoto, Y. Kariya, S. Sugawara, S. Hakomori, K. Nitta
• Journal: International Journal of Oncology
• Published: 2014;44(2):377-84
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is a highly aggressive tumor with poor prognosis. An effective drug for treatment of malignant mesothelioma is greatly needed. Sialic acid-binding lectin (SBL) isolated from oocytes of Rana catesbeiana is a multifunctional protein which has lectin activity, ribonuclease activity and antitumor activity, so it could be developed as a new type of anticancer drug. The validity of SBL for treatment of malignant mesothelioma was assessed using three malignant mesotheliomas and a non-malignant mesothlial cell line. Effectiveness of combinatorial treatment of SBL and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) was also elucidated and characterized. SBL induced tumor-selective cytotoxicity that was attributed to induction of apoptosis. Combinatorial treatment of SBL and TRAIL showed synergistic apoptosis-inducing effect. Additional experiments revealed that Bid was the mediating molecule for the synergistic effect in SBL and TRAIL. These results suggested that SBL could be a promising candidate for the therapeutics for malignant mesothelioma. Furthermore, the combinatorial treatment of SBL and TRAIL could be an effective regimen against malignant mesothelioma.

In plain English

This was a laboratory study on cell lines grown in dishes. It did not study people or asbestos exposure. The authors tested sialic acid-binding lectin (SBL), a protein from bullfrog (Rana catesbeiana) eggs. They used three malignant mesothelioma cell lines (H28, MESO-1, MESO-4) and one non-malignant mesothelial cell line (Met-5A). After SBL at 5, 10 and 20 µM, colony formation was reported as:

• below 70, 30 and 5% for MESO-1
• 20, 15 and 5% for MESO-4
• below 5% for H28 at all concentrations
• 90, 65 and 60% for Met-5A

A marker of apoptosis (programmed cell death) appeared in all three mesothelioma lines but not in Met-5A. In H28 cells, SBL alone left 66.7% of cells viable and TRAIL alone left 70.9%. The two together lowered viability to 24.7%. The authors read combination index values of 0.63 and 0.68 as synergy, meaning a combined effect greater than the two treatments added together. When the protein Bid was knocked down in H28 cells, the extra apoptosis from the combination was reduced. The authors concluded, from these cell experiments, that SBL with TRAIL can be an effective treatment for malignant mesothelioma.

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) experiments on cultured cell lines
• Who was studied: Three malignant mesothelioma cell lines and one immortalized non-malignant mesothelial cell line. NCI-H28 and Met-5A came from the American Type Culture Collection; ACC-MESO-1 and ACC-MESO-4 came from Riken Cell Bank, Japan. The combination and Bid experiments used mainly H28 cells.
• Exposure: Treatment of cells with sialic acid-binding lectin (SBL) from bullfrog (Rana catesbeiana) oocytes, alone and combined with TRAIL (tumor necrosis factor-related apoptosis inducing ligand). Asbestos exposure was not studied.
• Main results:
  • At SBL concentrations of 5, 10 and 20 µM, colony formation was reported as below 70, 30 and 5% for MESO-1 cells and 20, 15 and 5% for MESO-4 cells.
  • Colony formation of H28 mesothelioma cells was below 5% at all SBL concentrations tested. For non-malignant Met-5A cells it was 90, 65 and 60% at 5, 10 and 20 µM.
  • SBL caused Annexin V binding (a marker of apoptosis) in all three mesothelioma cell lines but not in non-malignant Met-5A cells.
  • In H28 cells, 24-hour treatment with SBL (5 µM) alone left 66.7% of cells viable and TRAIL (2 ng/ml) alone left 70.9%.
  • In H28 cells, SBL and TRAIL combined lowered viability to 24.7%.
  • Combination index values were 0.63 (SBL fixed at 0.5 µM) and 0.68 (TRAIL fixed at 1 ng/ml). The authors interpreted these values as synergy.
  • Annexin V binding increased significantly with the combined treatment in H28 cells but not in Met-5A cells.
  • Knocking down Bid with siRNA significantly reduced the extra Annexin V binding seen with the combined treatment in H28 cells.
• The authors' conclusion: The authors concluded that their results suggest the combination of SBL and TRAIL can be an effective treatment for malignant mesothelioma.

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, Malignant Mesothelioma, Prognosis, Necrosis, Synergistic Effect.

Related studies

• Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo — T. Tatsuta, T. Satoh, et al. (2018)
• Synergistic antitumor activity of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with carboplatin and pemetrexed in malignant pleural mesothelioma — G. Pasello, L. Urso, et al. (2014)
• Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway — K.H. Kim, J.I. Chae, et al. (2016)
• Phosphatidylinositol Induces Caspase-Independent Apoptosis of Malignant Pleural Mesothelioma Cells by Accumulating AIF in the Nucleus — S. Kanemura, A. Tsuchiya, et al. (2015)
• TRAIL and proteasome inhibitors combination induces a robust apoptosis in human malignant pleural mesothelioma cells through Mcl-1 and Akt protein cleavages — B.Z. Yuan, J. Chapman, et al. (2013)
• Antitumor effects of TRAIL-expressing mesenchymal stromal cells in a mouse xenograft model of human mesothelioma — M.J. Lathrop, E.K. Sage, et al. (2015)

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