Evaluation of intracavitary administration of curcumin for the treatment of sarcomatoid mesothelioma

Our plain-English summary of Evaluation of intracavitary administration of curcumin for the treatment of sarcomatoid mesothelioma, by D.L. Pouliquen, B. Nawrocki-Raby, J. Nader, et al (Oncotarget, 2017).

The study

• Authors: D.L. Pouliquen, B. Nawrocki-Raby, J. Nader, S. Blandin, M. Robard, P. Birembaut, M. Grégoire
• Journal: Oncotarget
• Published: 2017;8(34):57552-57573
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A rat model of sarcomatoid mesothelioma, mimicking some of the worst clinical conditions encountered, was established to evaluate the therapeutic potential of intracavitary curcumin administration. The M5-T1 cell line, selected from a collection established from F344 rats induced with asbestos, produces tumors within three weeks, with extended metastasis in normal tissues, after intraperitoneal inoculation in syngeneic rats. The optimal concentration/time conditions for killing M5-T1 cells with curcumin were first determined in vitro. Secondly, the potential of intraperitoneal curcumin administration to kill tumor cells in vivo was evaluated in tumor-bearing rats, in comparison with a reference epigenetic drug, SAHA. Both agents administered at days 21 and 26 after tumor challenge produced necrosis within the solid tumors at day 28. However, tumor tissue necrosis induced with curcumin was much more extensive than with SAHA, and was characterized by infiltration with mononuclear phagocytic cells. In contrast, tumor tissue treated with SAHA contained foci of resistant cells and was infiltrated by many isolated CD8+ cells. The treatment of tumor-bearing rats with 1.5 mg/kg curcumin on days 7, 9, 11 and 14 after tumor challenge dramatically reduced the mean total tumor mass at day 16. Clusters of CD8+ T lymphocytes were observed at the periphery of small residual tumor masses in the peritoneal cavity, which presented a significant reduction in mitotic index, IL6 and vimentin expression compared with tumors in untreated rats. These data open up interesting new prospects for the therapy of sarcomatoid mesothelioma with curcumin and its derivatives.

In plain English

This was a study in rats and cultured cells, not people. The authors used a mesothelioma cell line, M5-T1, from a rat whose tumors had been induced by crocidolite asbestos injected into the abdomen. The cells had a sarcomatoid character. In dishes, 100 µM curcumin killed almost all M5-T1 cells after 4 hours, while 10 µM SAHA or 10 µM cisplatin produced only a modest drop in cells. Rats were then given the tumor cells into the abdomen and treated by injections into the abdominal cavity. In groups of three rats, two doses of curcumin or SAHA did not visibly shrink tumors, but curcumin-treated rats had significantly more tumor tissue death than SAHA-treated rats or controls. In the article's third experiment, six rats given four doses of 1.5 mg/kg curcumin had a significantly lower mean total tumor mass at day 16 than six control rats injected with the solvent alone. Four of those six had no metastases in the liver, pancreas and diaphragm. Their residual tumors showed clusters of CD8+ immune cells and fewer dividing cells. The authors concluded that the data open new prospects for curcumin in treating sarcomatoid 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: Animal experiment (three successive experiments in rats) combined with in vitro cell-culture experiments
• Who was studied: Fischer F344 rats injected intraperitoneally with the rat mesothelioma cell line M5-T1. Experiment E1 used 3 male and 3 female rats. Experiment E2 used young male rats (8 weeks): 3 given curcumin, 3 given SAHA and 3 vehicle-only controls. Experiment E3 used 12 older male rats (16 weeks): 6 given curcumin and 6 vehicle-only controls. Cultured M5-T1 cells and a non-tumorigenic rat mesothelial cell line (F1-0e) were also tested.
• Exposure: The tumor cell line came from rats in which mesothelioma was induced with 10 mg crocidolite fibers injected intraperitoneally. The treatments studied were intraperitoneal curcumin (750 µg/kg twice in E2; 1.5 mg/kg four times in E3) and SAHA (50 mg/kg twice in E2). Cisplatin was tested only in vitro. Control rats received only the vehicle (DMSO in saline).
• Main results:
  • In vitro, 100 µM curcumin killed almost all M5-T1 tumor cells after 4 hours of treatment.
  • In vitro, 10 µM SAHA or 10 µM cisplatin produced only a modest decrease in M5-T1 cells compared with control wells.
  • In experiment E2, rats treated twice with SAHA or curcumin showed no visible reduction in tumor mass.
  • In experiment E2, tumor necrosis in the invaded omentum was significantly greater in curcumin-treated rats than in SAHA-treated or control rats.
  • In experiment E2, curcumin-treated rats had a significantly higher density of monocytes/macrophages in tumors than control or SAHA-treated rats.
  • In experiment E2, SAHA-treated rats had a significantly higher density of CD8+ cells in tumors than curcumin-treated or control rats.
  • In experiment E3, the 6 rats given four injections of 1.5 mg/kg curcumin had a significantly lower mean total tumor mass than the 6 vehicle-only controls. Exact values are shown only in a figure.
  • Four of the six curcumin-treated rats in experiment E3 had no metastases in the liver, pancreas and diaphragm, and only small residual tumor masses.
  • In that subgroup, clusters of large CD8+ T lymphocytes were seen at the edges of the residual tumors.
  • Residual tumors in curcumin-treated rats had significantly fewer mitoses per field than tumors in control rats. They also showed decreased IL6 and vimentin staining.
• The authors' conclusion: The authors concluded that the data open up new prospects for treating malignant mesothelioma with curcumin, particularly the sarcomatoid subtype, and that future studies should determine the best sequence and doses.

Topics

Medical terms in this study, explained in our Lexicon: Sarcomatoid, Mesothelioma, Metastasis, Necrosis, Peritoneal Cavity, Mitotic Index.

Related studies

• Local treatment of malignant pleural mesothelioma with intracavitary cytosine-arabinoside and cisplatin — E. Aitini, E. Pasquini, et al. (1992)
• Subcutaneous seeding after ultrasound-guided placement of intrapleural catheter. An unusual complication of the intracavitary palliative treatment of pleural mesothelioma — S. Sartori, I. Nielsen, et al. (1999)
• Treatment of bronchial fistula after extraplural pneumonectomy using flexible bronchoscopy with the administration of OK432, fibroblast growth factor basic and fibrin glue sealant — N. Kondo, M. Hashimoto, et al. (2020)
• Computed tomography in the evaluation of malignant pleural mesothelioma-Association of tumor size to a sarcomatoid histology, a more advanced TNM stage and poor survival — J. Paajanen, S. Laaksonen, et al. (2018)
• Current concepts in the evaluation and treatment of patients with diffuse malignant peritoneal mesothelioma — K. Turner, S. Varghese, et al. (2012)
• Malignant pleural mesothelioma: role of CT, MRI, and PET/CT in staging evaluation and treatment considerations — M.T. Truong, C. Viswanathan, et al. (2013)

Browse more research in Oncotarget, or return to medical research.