Identification of Cembrane Diterpenoids from Sinularia sp. That Reduce the Viability of Diffuse Pleural Mesothelioma Cell Lines

Our plain-English summary of Identification of Cembrane Diterpenoids from Sinularia sp. That Reduce the Viability of Diffuse Pleural Mesothelioma Cell Lines, by M. Orfanoudaki, A.F. Shaikh, D. Wang, et al (Journal of Natural Products, 2025).

The study

• Authors: M. Orfanoudaki, A.F. Shaikh, D. Wang, V. Singh, L. Du, J.A. Wilson, A. Wamiru, E.I. Goncharova, N. Pruett, C.D. Hoang, B.A.P. Wilson, B.R. O'Keefe
• Journal: Journal of Natural Products
• Published: 2025;88(9):2193-2203
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Diffuse pleural mesothelioma (DPM) is a rare but aggressive late-onset cancer. A high-throughput screen of a natural product fraction library identified fractions derived from an aqueous extract of Sinularia sp. soft coral that reduced the viability of DPM cell lines. Bioassay-guided fractionation of the parent extract resulted in the identification of 13 cembrane diterpenoids, including nine new natural products sinulariolones B-J (1-4, and 7-11), as the active principles. The planar structures of the new compounds were established by the analysis of NMR spectroscopic and MS spectrometric data. Their relative and absolute configurations were determined using a combined approach, including NOESY interpretation, modified Mosher's method, ECD simulation, and single-crystal X-ray diffraction. All pure metabolites were tested for their effects on the viability of the DPM cell lines, and compounds 2, 3, 8, and 9 demonstrated low micromolar potency against these cancer cell lines.

In plain English

This was a laboratory study of chemicals from a soft coral, tested on cells grown in dishes. It did not study asbestos exposure or patients. The authors screened about 34,000 fractionated natural product extracts against two patient-derived diffuse pleural mesothelioma cell lines, MB24 (sarcomatoid) and MB52 (epithelial). Most samples did not significantly reduce cell viability (median reading 81% viability). Fractions from a Sinularia sp. soft coral, collected in Vanuatu in December 2000, reduced the viability of MB52 cells. Further separation yielded 13 cembrane diterpenoids, nine of them new (named sinulariolones B to J). Four new compounds (2, 3, 8 and 9) were tested on both mesothelioma cell lines and on a normal pleural cell line, NP1. Their LD50 values ranged from 11.4 to 27.4 micromolar in MB24 cells, 4.7 to 12.5 micromolar in MB52 cells, and 5.2 to 15.9 micromolar in NP1 cells. The remaining compounds had LD50 values above 50 micromolar. The authors concluded that some compounds had interesting bioactivities against human cell line models of 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) drug-discovery study: high-throughput screening of natural product fractions on mesothelioma cell lines, followed by isolation, chemical structure determination and cell viability testing of compounds
• Who was studied: No people were studied. The study used two patient-derived diffuse pleural mesothelioma cell lines, MB24 (sarcomatoid) and MB52 (epithelial), obtained from MesoBank, U.K., plus a patient-derived normal pleura mesothelial cell line, NP1, used for comparison
• Exposure: Not an asbestos exposure study; asbestos is mentioned only as background. Cells were treated with natural product fractions at 10 micrograms per mL in the screen. They were then treated with pure compounds 2, 3, 8 and 9, isolated from an aqueous extract of a Sinularia sp. soft coral collected at 10 m depth in Vanuatu, at 12 concentrations from 200 to 2 micromolar for 72 hours
• Main results:
  • In the primary screen of about 34,000 marine fractions against the two mesothelioma cell lines, most samples did not significantly reduce viability in either cell line (median reading 81% viability). 358 substances showed nonspecific activity, reducing viability in both lines
  • Isolation work guided by the cell tests on the Sinularia sp. extract identified 13 cembrane diterpenoids: nine new compounds (1 to 4 and 7 to 11) and four previously known compounds (5, 6, 12 and 13)
  • Compound 2 LD50 values: 11.4 micromolar in MB24 (sarcomatoid mesothelioma), 4.7 micromolar in MB52 (epithelial mesothelioma), 5.2 micromolar in NP1 (normal pleura)
  • Compound 3 LD50 values: 13.3 micromolar in MB24, 7.1 micromolar in MB52, 7.8 micromolar in NP1
  • Compound 8 LD50 values: 14.2 micromolar in MB24, 7.9 micromolar in MB52, 15.7 micromolar in NP1
  • Compound 9 LD50 values: 27.4 micromolar in MB24, 12.5 micromolar in MB52, 15.9 micromolar in NP1
  • The other compounds had LD50 values above 50 micromolar, and the authors did not report them
• The authors' conclusion: The authors concluded that they had identified nine new cembrane diterpenoids plus four known ones, some with interesting bioactivities against human cell line models of mesothelioma. They also said they had introduced a mesothelioma-specific screening platform that could potentially reveal further candidate compounds

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, X-Ray Diffraction (XRD).

Related studies

• Cytotoxic Microspinosamides from the Marine Sponge Geodia microspinosa That Decrease Diffuse Pleural Mesothelioma Viability — M. Orfanoudaki, D. Wang, et al. (2026)
• Pharmacological inhibition of CDK4/6 impairs diffuse pleural mesothelioma 3D spheroid growth and reduces viability of cisplatin-resistant cells — A. Costa, I.M. Forte, et al. (2024)
• Reduced cell viability and apoptosis induction in human thyroid carcinoma and mesothelioma cells exposed to cidofovir — S. Catalani, F. Palma, et al. (2017)
• Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines — L. Cortes-Dericks, L. Froment, et al. (2016)
• Variation in drug sensitivity of malignant mesothelioma cell lines with substantial effects of selenite and bortezomib, highlights need for individualized therapy — A. Szulkin, G. Nilsonne, et al. (2013)
• Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines — A.M. Hand, K. Husgafvel-Pursiainen, et al. (1992)

Browse return to medical research.