Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma

Our plain-English summary of Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma, by A. Luna-Nophal, F. Díaz-Castillo, V. Izquierdo-Sánchez, et al (Marine Drugs, 2025).

The study

• Authors: A. Luna-Nophal, F. Díaz-Castillo, V. Izquierdo-Sánchez, J.B. Velázquez-Fernández, M. Orozco-Morales, L. Lara-Mejía, J. Bernáldez-Sarabia, N. Sánchez-Campos, O. Arrieta, J. Díaz-Chávez, J.I. Castañeda-Sánchez, A.F. Licea-Navarro, S. Muñiz-Hernández
• Journal: Marine Drugs
• Published: 2025;23(1)
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare neoplasm with increasing incidence and mortality rates. Although recent advances have improved the overall prognosis, they have not had an important impact on survival of patients with MPM, such that more effective treatments are needed. Some species of marine snails have been demonstrated to be potential sources of novel anticancer molecules. This study analyzed the anticancer effects in vitro and in vivo of two peptides found in C. californicus. The effects of s-cal14.1b and s-cal14.2b on cell proliferation, apoptosis, and cytotoxicity were evaluated in 2D and 3D cultures of MPM-derived cells. Proteomics analysis of 3D cultures treated with conotoxins was performed to examine changes in expression or abundance. And the therapeutic effects of both conotoxins were evaluated in MPM mouse xenografts. s-cal14.1b and s-cal14.2b induced apoptosis and cytotoxicity in 2D and 3D cultures. However, only s-cal14.1b modified spheroid growth. Approximately 600 proteins exhibited important differential expression, which was more heterogeneous in H2452 vs MSTO-211H spheroids. The in silico protein functional analysis showed modifications in the biological pathways associated with carcinogenesis. CAPN1, LIMA1, ANXA6, HUWE1, PARP1 or PARP4 proteins could be potential cell targets for conotoxins and serve as biomarkers in MPM. Finally, we found that both conotoxins reduced the tumor mass in MPM xenografts; s-cal14.1b reached statistical significance. Based on these results, s-cal14.1b and s-cal14.2b conotoxins could be potential therapeutic drugs for MPM neoplasms with no apparent side effects on normal cells.

In plain English

This laboratory and animal study tested two synthetic peptides, s-cal14.1b and s-cal14.2b, based on venom toxins (conotoxins) of the snail Californiconus californicus, against malignant pleural mesothelioma. It did not study asbestos exposure. The authors used mesothelioma cell lines H2452 and MSTO-211H, grown flat and as three-dimensional clusters (spheroids), and normal lung cells (MRC-5). They used mice carrying MSTO-211H tumors, five per group. In flat cultures, neither peptide slowed normal lung cell growth; s-cal14.2b slowed H2452 growth at all tested concentrations at 24 hours; s-cal14.1b slowed no cell line. However, s-cal14.1b significantly reduced H2452 spheroid volume during the growth period (p = 0.024). Both peptides induced programmed cell death (apoptosis) in flat H2452 cultures. In spheroids, both caused cell damage in MSTO-211H; in H2452, only s-cal14.2b caused a statistically significant effect. Several hundred proteins changed level after treatment. In mice, final tumor volume with s-cal14.1b differed statistically significantly from controls. Tumors treated with s-cal14.2b grew less than controls. The authors concluded the peptides showed antitumor properties. They cautioned that finding no toxicity in normal cells or mice does not necessarily mean they are safe for humans.

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 (cell culture) experiments with protein analysis by mass spectrometry, plus an animal experiment in mice carrying human mesothelioma tumors (xenografts)
• Who was studied: Mesothelioma-derived cell lines MSTO-211H and H2452, and the normal lung cell line MRC-5; athymic (immune-deficient) mice inoculated with MSTO-211H cells, five mice per experimental group
• Exposure: No asbestos exposure was studied. The exposure was the synthetic conotoxins s-cal14.1b and s-cal14.2b. In cell cultures they were given at 20, 30 and 50 µM. In mice they were given intravenously at 0.5 mg/kg.
• Main results:
  • In flat (monolayer) cultures, normal lung cells (MRC-5) showed no slowing of growth with either conotoxin at any exposure time
  • In flat cultures, s-cal14.2b slowed growth of H2452 cells at 24 hours at all tested concentrations
  • s-cal14.1b showed no growth-inhibiting effect on any cell line in flat cultures
  • Both conotoxins induced apoptosis in flat H2452 cultures, higher at 48 hours. Flat MSTO-211H cultures showed no differences in apoptosis.
  • In H2452 spheroids during the growth period, the volume of spheroids exposed to s-cal14.1b was smaller than control, a statistically significant difference (p = 0.024)
  • Both conotoxins caused cell damage (cytotoxicity) in MSTO-211H spheroids in both culture periods. In H2452 spheroids, only s-cal14.2b caused a significant cytotoxic effect.
  • Proteins with at least a 1.5-fold change versus untreated spheroids numbered 619 (day 4) and 646 (day 8) in MSTO-211H spheroids, and 593 (day 5) and 614 (day 9) in H2452 spheroids
  • In mice, tumors treated with s-cal14.1b grew more slowly, and their final tumor volume differed statistically significantly from untreated controls
  • In mice, tumors treated with s-cal14.2b grew less than in untreated controls; the article does not report this difference as statistically significant
  • The authors proposed proteins for further research as possible targets, based on their change in expression after treatment
• The authors' conclusion: The authors concluded that their work demonstrated antitumor properties of the two synthetic peptides in malignant pleural mesothelioma models (cell cultures and mice)
• Limitations the authors state:
  • Finding no toxicity in normal cells or mice does not necessarily mean the peptides are safe for humans
  • The conotoxins were not compared with a chemotherapy drug used to treat mesothelioma
  • There is a lack of information about the specific targets of the conotoxins in mesothelioma cells

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: Pleural Mesothelioma, Neoplasm, Prognosis, Apoptosis, Carcinogenesis, Biomarker, Statistical Significance.

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