Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma

Our plain-English summary of Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma, by D.L. Pouliquen, M. Malloci, A. Boissard, et al (International Journal of Molecular Sciences, 2022).

The study

• Authors: D.L. Pouliquen, M. Malloci, A. Boissard, C. Henry, C. Guette
• Journal: International Journal of Molecular Sciences
• Published: 2022;23(22)
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Curcumin exhibits both immunomodulatory properties and anticarcinogenic effects which have been investigated in different experimental tumor models and cancer types. Its interactions with multiple signaling pathways have been documented through proteomic studies on malignant cells in culture; however, in vivo approaches are scarce. In this study, we used a rat model of highly invasive peritoneal mesothelioma to analyze the residual tumor proteomes of curcumin-treated rats in comparison with untreated tumor-bearing rats (G1) and provide insights into the modifications in the tumor microenvironment/malignant cell crosstalk. The cross-comparing analyses of the histological sections of residual tumors from two groups of rats given curcumin twice on days 21 and 26 after the tumor challenge (G2) or four times on days 7, 9, 11 and 14 (G3), in comparison with G1, identified a common increase in caveolin-1 which linked with significant abundance changes affecting 115 other proteins. The comparison of G3 vs. G2 revealed additional features for 65 main proteins, including an increase in histidine-rich glycoprotein and highly significant abundance changes for 22 other proteins regulating the tumor microenvironment, linked with the presence of numerous activated T cells. These results highlight new features in the multiple actions of curcumin on tumor microenvironment components and cancer cell invasiveness.

In plain English

This laboratory experiment in male F344 rats did not study people or asbestos exposure. The authors injected a rat mesothelioma cell line (M5-T1) into the abdomen of rats to grow peritoneal mesothelioma tumors. They compared tumors from untreated rats (G1, 2 rats chosen from 9) with residual tumors from rats given curcumin injections twice, on days 21 and 26 (G2, 3 rats), or four times, on days 7, 9, 11 and 14 (G3, 6 rats). From G3, the residual tumors of 3 rats with dramatically reduced total tumor mass were selected. Under the microscope, tumors from both treated groups showed lower cell density and numerous lymphocytes, a type of immune cell. Protein measurements found 116 proteins that changed in both treated groups compared with untreated rats (50 increased, 66 decreased), including an increase in caveolin-1. Comparing G3 with G2 identified 65 further proteins (45 increased, 20 decreased), including an increase in histidine-rich glycoprotein, along with a decrease in CD4. The authors concluded that repeated curcumin produced significant changes in a set of proteins associated with the tumor microenvironment.

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: histology and proteomic (protein abundance) analysis of tumors in rats treated or not treated with curcumin
• Who was studied: Male F344 rats injected in the peritoneal cavity with the M5-T1 rat mesothelioma cell line on day 0. The groups were G1 untreated (n = 2, selected from 9 untreated tumor-bearing rats), G2 (n = 3) and G3 (n = 6). For analysis, the small residual tumors from 3 rats were selected, representing the subgroup showing a dramatic reduction in total tumor masses.
• Exposure: No asbestos or fiber exposure was studied. Rats were given curcumin injected into the peritoneal cavity: G2 received 750 µg/kg on days 21 and 26, and G3 received 1.5 mg/kg on days 7, 9, 11 and 14 after tumor cell injection.
• Main results:
  • Compared with untreated G1 tumors, tumors from both curcumin-treated groups (G2 and G3) showed a decrease in cell density.
  • G2 and G3 tumor tissues contained numerous lymphocytes.
  • G2 vs. G1: of 3093 proteins detected, 693 showed significant (p less than 0.05) abundance changes, with 290 increased and 403 decreased.
  • G3 vs. G1: of 3096 proteins detected, 833 showed significant changes, with 514 increased and 319 decreased.
  • 116 proteins changed in common in both treated groups relative to G1: 50 increased and 66 decreased.
  • Caveolin-1 was among the proteins that increased in both treated groups.
  • Comparing four-dose G3 rats with G2 and G1 rats (p less than 0.0001 in at least one comparison) gave 65 proteins: 45 increased and 20 decreased.
  • In G3, CD4 decreased significantly compared with both G1 and G2. Cd8a showed a tendency toward an increase in G3 vs. G2.
  • Among immune-related proteins in the G3-specific list, histidine-rich glycoprotein increased.
• The authors' conclusion: The authors concluded that repeated curcumin administration to tumor-bearing rats produces significant abundance changes in a set of proteins associated with the tumor microenvironment. They wrote that the changes in immunological markers tend to confirm their hypothesis of a systemic antitumor effect.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Peritoneal Mesothelioma, Tumor Microenvironment, Glycoprotein.

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