Central Role of Cell Cycle Regulation in the Antitumoral Action of Ocoxin

Abstract

Nutritional supplements which include natural antitumoral compounds could represent safe and efficient additives for cancer patients. One such nutritional supplement, Ocoxin Oral solution (OOS), is a composite formulation that contains several antioxidants and exhibits antitumoral properties in several in vitro and in vivo tumor conditions. Here, we performed a functional genomic analysis to uncover the mechanism of the antitumoral action of OOS. Using in vivo models of acute myelogenous leukemia (AML, HEL cells, representative of a liquid tumor) and small-cell lung cancer (GLC-8, representative of a solid tumor), we showed that OOS treatment altered the transcriptome of xenografted tumors created by subcutaneously implanting these cells. Functional transcriptomic studies pointed to a cell cycle deregulation after OOS treatment. The main pathway responsible for this deregulation was the E2F–TFDP route, which was affected at different points. The alterations ultimately led to a decrease in pathway activation. Moreover, when OOS-deregulated genes in the AML context were analyzed in patient samples, a clear correlation with their levels and prognosis was observed. Together, these data led us to suggest that the antitumoral effect of OOS is due to blockade of cell cycle progression mainly caused by the action of OOS on the E2F–TFDP pathway.

Antitumoral Properties of the Nutritional Supplement Ocoxin Oral Solution: A Comprehensive Review

“…In hepatocellular carcinoma, addition of OOS provoked an increase in the amount of cyclin B1 that accompanied cell cycle arrest in G2 [70]. An unbiased microarray study performed on in vivo lung cancer and acute myeloid leukemia cells derived from xenografts prepared in mice, followed by functional transcriptomic evaluation revealed the cell cycle-related functions as the major target functions affected by OOS [66]. These studies confirmed the regulation of p27 and the Rb pathway by OOS in both types of xenografted tumors.…”

“…The effect of OOS on the cell cycle, as identified in the biochemical [65] and the in silico analyses [66], opens an interesting possibility for its application in a particular subtype of breast cancer. In fact, hormonal breast tumors, characterized by the presence of estrogen and progesterone receptors, are particularly sensitive to the action of CDK4/6 inhibitors.…”

“…Interestingly, OOS increased a number of cytokines in the serum of these mice, including IL-6. These studies were complemented by in vivo microarray analyses of the effect of OOS on the transcriptomic landscape of leukemic cells [66]. They showed that OOS caused deregulation of 150 genes.…”

<p>The Natural Product Fucoidan Inhibits Proliferation and Induces Apoptosis of Human Ovarian Cancer Cells: Focus on the PI3K/Akt Signaling Pathway</p>

“…The abnormality of cell cycle litter-controlling factors is the main reason for the uncontrolled proliferation of cancer cells and the resistance of apoptotic cells can easily lead to the drug resistance of cancer cells. 34,36 Our data show that fucoidan induced the accumulation of SKOV-3 and Caov-3 cells in the G0/G1 phase, which was accompanied by a decreased numbers of cells in the S and G2/M phases. At the same time, fucoidan increased the level of cyclin-dependent kinase inhibitor 1A (P21) and decreased the Rb phosphorylation at Ser795.…”

“…34 Many growth factors, cytokines, hormones, and oncogene products regulate DNA metabolism through the cell cycle. 35,36 Studies of the cell cycle have deepened the understanding of the mechanism of tumorigenesis. As an antineoplastic drug, fucoidan has been found to induce G0/G1 phase arrest in SKOV-3 and Caov-3 cells (Figure 2A).…”