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

Daniel L Pouliquen,Alice Boissard,Catherine Guette,Olivier Coqueret,Cécile Henry,Stéphanie Blandin

doi:10.3390/ijms22168566

Daniel L Pouliquen, Alice Boissard + Show 4 more

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https://doi.org/10.3390/ijms22168566

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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.

Highlights

Curcumin belongs to a category of bioactive compounds with the propensity to target multiple signaling pathways that are crucial for tumor development [1]
Our observations suggest that multiple intraperitoneal administration of curcumin produced effects in secondary lymphoid organs of tumor-bearing rats at two complementary levels
Close to the initial location of tumor development, curcumin restored both red and white pulp functions and the delicate balance observed between these two compartments in normal animals, shown by the return to normal abundances of 53 proteomic biomarkers

Summary

Introduction

Curcumin belongs to a category of bioactive compounds with the propensity to target multiple signaling pathways that are crucial for tumor development [1]. This molecule provides a diversity of interactions explained by its binding to numerous proteins via a unique symmetrical structure combining a central keto-enol tautomer, flexible a,bunsaturated b-diketone linkers, and terminal o-methoxyphenolic groups [2]. In line with the concept of polypharmacology, its mechanism of action suggests that it modulates multiple sensitive nodes belonging to a network of interacting targets [3]. This new concept offers a strategy to overcome drug resistance [4]. Trials have demonstrated clinical evidence in prevention and treatment, including synergistic effects on the efficacy of current cancer drugs [5]

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