The Anticancer Efficacy of Plasma-Oxidized Saline (POS) in the Ehrlich Ascites Carcinoma Model In Vitro and In Vivo.

Walison Augusto Silva Brito,William Capellari Fumegali,Sander Bekeschus,Lea Miebach,Larissa Juliani Sanches,Thiago Daniel Henrique Do Nascimento,Eric Freund,Gabriella Pasqual-Melo,Alessandra Lourenço Cecchini,Joyce Hellen Ribeiro Dionísio

doi:10.3390/biomedicines9080932

Abstract

Cold physical plasma, a partially ionized gas rich in reactive oxygen species (ROS), is receiving increasing interest as a novel anticancer agent via two modes. The first involves its application to cells and tissues directly, while the second uses physical plasma-derived ROS to oxidize liquids. Saline is a clinically accepted liquid, and here we explored the suitability of plasma-oxidized saline (POS) as anticancer agent technology in vitro and in vivo using the Ehrlich Ascites Carcinoma (EAC) model. EAC mainly grows as a suspension in the peritoneal cavity of mice, making this model ideally suited to test POS as a putative agent against peritoneal carcinomatosis frequently observed with colon, pancreas, and ovarium metastasis. Five POS injections led to a reduction of the tumor burden in vivo as well as in a decline of EAC cell growth and an arrest in metabolic activity ex vivo. The treatment was accompanied by a decreased antioxidant capacity of Ehrlich tumor cells and increased lipid oxidation in the ascites supernatants, while no other side effects were observed. Oxaliplatin and hydrogen peroxide were used as controls and mediated better and worse outcomes, respectively, with the former but not the latter inducing profound changes in the inflammatory milieu among 13 different cytokines investigated in ascites fluid. Modulation of inflammation in the POS group was modest but significant. These results promote POS as a promising candidate for targeting peritoneal carcinomatosis and malignant ascites and suggest EAC to be a suitable and convenient model for analyzing innovative POS approaches and combination therapies.

Highlights

We investigated the antitumor efficacy of plasma-oxidized saline (POS) in an Ehrlich Ascites Carcinoma (EAC) model (Figure 1a)
We observed a decline in pH (Figure 1c), which was within the physiological range of medically approved saline solutions
H2 O2 production is typical in POS, and deposition of H2 O2 yielded a final concentration of 90 μM in POS

Summary

Introduction

Cancer continues to be a devastating disease, motivating new research lines for therapy. Tumors of the peritoneal cavity are frequently lethal, as these metastases provoke organ dysfunction and further systemic tumor dissemination [1]. This is especially pronounced in colon, pancreatic, gastric, and ovarian cancer. Current strategies targeting peritoneal carcinomatosis (PC) involve peritoneal lavage with preheated liquids that contain tumor-toxic agents, a procedure called hyperthermal intraperitoneal chemotherapy (HIPEC), which often is combined with cytoreductive surgery [2]. HIPEC, often demonstrates severe side effects at appropriate to modest antitumor

Methods

Results

Discussion

Conclusion