Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo

Our plain-English summary of Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo, by T. Tatsuta, T. Satoh, S. Sugawara, et al (PloS One, 2018).

The study

• Authors: T. Tatsuta, T. Satoh, S. Sugawara, A. Hara, M. Hosono
• Journal: PloS One
• Published: 2018;13(1):e0190653
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is an aggressive cancer that results from exposure to asbestos. The therapeutic options for this type of cancer are limited; therefore, the development of novel therapeutic agents is urgently required. Sialic acid-binding lectin isolated from Rana catesbeiana oocytes (cSBL) is a novel therapeutic candidate for cancer, which exhibits antitumor activity mediated through RNA degradation. In the present study, we evaluated the effect of cSBL in vitro and in vivo. Xenograft-competent H2452 and MSTO human mesothelioma cell lines were treated with cSBL, and the pathway by which cSBL induces apoptosis was analyzed. In vivo studies were performed using nude mice inoculated with one of the two cell lines, and the effects of cSBL and pemetrexed were monitored simultaneously. Furthermore, the pharmacological interactions between the three agents (pemetrexed, cisplatin and cSBL) were statistically assessed. It was demonstrated that cSBL treatments caused morphological and biochemical apoptotic changes in both cell lines. Caspase cascade analysis revealed that an intrinsic pathway mediated cSBL-induced apoptosis. The administration of cSBL significantly inhibited tumor growth in two xenograft models, without any adverse effects. Furthermore, the combination index and dose reduction index values indicated that the cSBL + pemetrexed combination showed the highest synergism, and thus potential for reducing dosage of each drug, compared with the other combinations, including the existing pemetrexed + cisplatin regimen. cSBL exerted prominent antitumor effects on malignant mesothelioma cells in vitro and in vivo, and showed favorable effects when combined with pemetrexed. These results suggest that cSBL has potential as a novel drug for the treatment of malignant mesothelioma.

In plain English

This was a laboratory study, not a study of people or of asbestos exposure. The authors tested cSBL, a protein taken from bullfrog eggs, on two human malignant mesothelioma cell lines, H2452 and MSTO. They grew the cells in dishes and also as tumors under the skin of nude mice. In dishes, cSBL significantly increased signs of programmed cell death (apoptosis). Annexin V-positive cells reached 16.13% of H2452 cells and 40.05% of MSTO cells at 72 hours. The enzyme caspase-9 switched on before caspase-8 and caspase-3, which the authors read as the intrinsic route of cell death. In mice (10 per group), no body-weight changes were seen in any group. In H2452 tumors, both cSBL and the chemotherapy drug pemetrexed significantly slowed growth compared with a PBS (saline) control. In MSTO tumors, only cSBL did. In dishes, cSBL plus pemetrexed showed the strongest combined effect of the pairings tested. The authors said they could not compare cSBL and pemetrexed directly because the dosing differed. They concluded that cSBL has potential as a novel 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 study: experiments on human mesothelioma cell lines in culture (in vitro) and on human mesothelioma tumors grown in mice (xenograft animal experiment)
• Who was studied: Two commercially obtained human malignant mesothelioma cell lines, NCI-H2452 and MSTO-211H. For the animal work, 5-week-old male nude mice carrying tumors of 100 to 150 mm3, split randomly into three groups of 10 mice each.
• Exposure: No asbestos exposure was studied. The treatment tested was cSBL, a sialic acid-binding lectin from bullfrog (Rana catesbeiana) eggs. In mice, cSBL was given at 2.5 mg/kg into the tumor twice per week for 4 weeks. Pemetrexed was given at 100 mg/kg into the abdomen on days 1 to 5 and 15 to 19, and PBS served as the control. In cell culture, cSBL, pemetrexed and cisplatin were also tested in pairs.
• Main results:
  • After 72 hours of cSBL treatment, the percentage of Annexin V-positive (apoptotic) cells was significantly increased: 16.13% of H2452 cells and 40.05% of MSTO cells.
  • In both cell lines treated with cSBL, caspase-9 was activated before caspase-8 and caspase-3, which the authors interpreted as involvement of the intrinsic apoptotic pathway.
  • In the mouse experiments, no body weight changes were observed in any group (PBS, pemetrexed or cSBL).
  • In mice with H2452 tumors, cSBL and pemetrexed each significantly inhibited tumor growth compared with PBS (P less than 0.05). The effect appeared earlier in the cSBL group (after 36 days of treatment) than in the pemetrexed group (after 47 days).
  • In mice with MSTO tumors, significant inhibition of tumor growth was seen only in the cSBL-treated group, after 29 days of treatment (P less than 0.05).
  • In H2452 cells in culture, all drug pairings were synergistic, and cSBL plus pemetrexed showed the highest synergistic effect at every concentration tested.
  • In MSTO cells in culture, all pairings were antagonistic at the two highest concentrations. The cSBL-containing pairings were highly synergistic in the mid-to-low concentration range. Pemetrexed plus cisplatin had low dose reduction index values at all concentrations.
• The authors' conclusion: The authors concluded that cSBL induced apoptosis in these mesothelioma cells and inhibited tumor growth in mouse xenograft models. In their results, cSBL plus pemetrexed was more effective in mesothelioma cells than pemetrexed plus cisplatin, and they concluded that cSBL has potential as a novel treatment for malignant mesothelioma.
• Limitations the authors state:
  • The authors could not directly compare the effects of cSBL and pemetrexed in mice because the two were given under different dosing conditions.
  • The maximal tolerated dose of cSBL was not determined; the authors said further studies are needed.
  • The authors stated that the reason pemetrexed had no effect in the MSTO xenografts is uncertain.

Topics

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

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

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• Temsirolimus inhibits malignant pleural mesothelioma growth in vitro and in vivo: synergism with chemotherapy — M.A. Hoda, A. Mohamed, et al. (2011)
• Combination of onconase and dihydroartemisinin synergistically suppresses growth and angiogenesis of non-small-cell lung carcinoma and malignant mesothelioma — R. Shen, J. Li, et al. (2016)
• Lectin binding properties of cells from serous effusion and peritoneal washing specimens — P.W. Shield (1989)
• Withaferin A inhibits the proteasome activity in mesothelioma in vitro and in vivo — H. Yang, Y. Wang, et al. (2012)

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