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Lymphoid Organ Proteomes Identify Therapeutic Efficacy Biomarkers Following the Intracavitary Administration of Curcumin in a Highly Invasive Rat Model of Peritoneal Mesothelioma

Our plain-English summary of Lymphoid Organ Proteomes Identify Therapeutic Efficacy Biomarkers Following the Intracavitary Administration of Curcumin in a Highly Invasive Rat Model of Peritoneal Mesothelioma, by D.L. Pouliquen, A. Boissard, C. Henry, et al (International Journal of Molecular Sciences, 2021).

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The study

Abstract

This study aimed to identify the proteomic changes produced by curcumin treatment following stimulation of the host immune system in a rat model of malignant mesothelioma. We analyzed the proteomes of secondary lymphoid organs from four normal rats, four untreated tumor-bearing rats, and four tumor-bearing rats receiving repeated intraperitoneal administrations of curcumin. Cross-comparing proteome analyses of histological sections of the spleen from the three groups first identified a list of eighty-three biomarkers of interest, thirteen of which corresponded to proteins already reported in the literature and involved in the anticancer therapeutic effects of curcumin. In a second step, comparing these data with proteomic analyses of histological sections of mesenteric lymph nodes revealed eight common biomarkers showing a similar pattern of changes in both lymphoid organs. Additional findings included a partial reduction of the increase in spleen-circulating biomarkers, a decrease in C-reactive protein and complement C3 in the spleen and lymph nodes, and an increase in lymph node purine nucleoside phosphorylase previously associated with liver immunodeficiency. Our results suggest some protein abundance changes could be related to the systemic, distant non-target antitumor effects produced by this phytochemical.

In plain English

This animal experiment did not involve asbestos. The authors injected M5-T1 mesothelioma cells into the abdomen of male F344 rats. Twelve rats formed three groups of four: normal rats, untreated tumor-bearing rats, and tumor-bearing rats given four abdominal injections of curcumin (1.5 mg/kg) between days 7 and 14. Spleens and mesenteric lymph nodes taken at euthanasia on day 16 were analyzed for proteins. Treated rats had significantly lower average tumor and spleen masses than untreated rats, and a distinct population of CD8+ T cells (a type of immune cell) appeared in their spleens. In the spleen, 83 proteins changed both with tumor growth and with curcumin. Of these, 55 that rose and 5 that fell with tumor growth moved back after curcumin and no longer differed significantly from normal rats. Thirteen of the 83 had already been linked to curcumin in earlier research. Eight proteins changed in a similar way in the spleen and the lymph nodes. The authors concluded that this tends to demonstrate an out-of-field systemic antitumor effect, probably related to curcumin causing widespread tumor cell death.

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 (laboratory rat model of peritoneal mesothelioma, with protein analysis of lymphoid organs)
  • Who was studied: 12 male F344 (Fisher) rats at the University of Nantes animal facility, France, in three groups of four: normal rats (G1), untreated tumor-bearing rats (G2), and curcumin-treated tumor-bearing rats (G3). Study dates are not given.
  • Exposure: No asbestos exposure was studied. Rats in G2 and G3 received a single abdominal injection of M5-T1 mesothelioma tumor cells (3 million cells) on day 0. G3 rats then received four abdominal injections of curcumin (1.5 mg/kg in 50% DMSO plus saline) on days 7, 9, 11 and 14. G1 and G2 rats received the vehicle (DMSO) only. All rats were euthanized on day 16, and their spleens and mesenteric lymph nodes were sampled for later analysis.
  • Main results:
    • Average total tumor mass and spleen mass were significantly lower in curcumin-treated rats (G3) than in untreated tumor-bearing rats (G2).
    • In curcumin-treated rats, metastatic nodules were absent from the peritoneal cavity and diaphragm, and only a few residual tumor masses were found.
    • The spleens of curcumin-treated rats contained a specific population of CD8+ T cells in the lymphoid sheath around the central artery.
    • 1483 proteins were detected in each spleen sample. Of the 83 spleen proteins of interest, 55 increased and 5 decreased with tumor progression (untreated vs normal rats). These then changed in the opposite direction with curcumin (treated vs untreated rats), and treated and normal rats showed no statistically significant difference (p greater than 0.05). The authors describe this as a return to normal values.
    • Thirteen of the 83 spleen proteins had already been reported in PubMed literature as associated with curcumin's therapeutic effects.
    • In mesenteric lymph nodes (1498 proteins detected per sample), eight proteins showed abundance changes similar to those seen in the spleen.
    • In lymph nodes, one protein specific to curcumin's effects was identified: purine nucleoside phosphorylase.
    • In the spleen, rises in several plasma proteins with tumor growth were only partly reversed by curcumin. In lymph nodes, only C-reactive protein changed in a way comparable to the spleen, and complement C3 also decreased after curcumin treatment.
  • The authors' conclusion: The authors concluded that the similar changes in eight proteins in the spleen and in lymph nodes far from the tumor tend to demonstrate an out-of-field systemic antitumor effect. They considered this probably related to curcumin causing massive necrosis/apoptosis (death) of tumor cells, and said the observations provide a basis for future mechanistic studies.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Peritoneal Mesothelioma, Mesothelioma.

Browse more research in International Journal of Molecular Sciences, or return to medical research.

How to cite it

Cite the study

D.L. Pouliquen, A. Boissard, C. Henry, S. Blandin, O. Coqueret, C. Guette. Lymphoid Organ Proteomes Identify Therapeutic Efficacy Biomarkers Following the Intracavitary Administration of Curcumin in a Highly Invasive Rat Model of Peritoneal Mesothelioma. International Journal of Molecular Sciences 2021;22(16). doi:10.3390/ijms22168566. PMID: 34445271.

Cite our summary

“Lymphoid Organ Proteomes Identify Therapeutic Efficacy Biomarkers Following the Intracavitary Administration of Curcumin in a Highly Invasive Rat Model of Peritoneal Mesothelioma.” AsbestosClaims.Law Library. https://asbestosclaims.law/library/research/lymphoid-organ-proteomes-identify-therapeutic-efficacy-biomarkers.

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