Ocoxin® oral solution slows down tumor growth in an experimental model of colorectal cancer metastasis to the liver in Balb/c mice

Abstract

Liver metastatic disease is the main cause of death in colorectal cancer (CRC) patients. During metastatic spread of the disease an imbalance in the oxidative stress and inflammation plays a crucial role in tumor progression. In order to improve the efficacy of current therapies, new complementary therapeutic approaches are being analyzed including biologically active compounds with low side effects. The anti-inflammatory and anti-oxidant properties of Ocoxin® oral solution (OOS) prompt us to analyze its effect on the metastatic development of CRC to the liver. First, in vitro effect of OOS in tumor cell viability and migration was analyzed. Second, in vivo effect of different dosage patterns and concentrations in the development of hepatic metastasis was analyzed by intrasplenic inoculation of C26 colon carcinoma cells in Balb/c mice. Third, the expression of alpha smooth muscle actin, caspase-3 and Ki-67 expression was quantified by immunohistochemistry, then gene expression levels of inflammatory factors were measured by quantitative RT-PCR. According to our results, OOS reduced tumor cell viability and migration in vitro. Moreover, in vivo daily administration of OOS from the 7th day after tumor cell inoculation decreased the total area and size of metastatic foci in the liver. Furthermore, cell proliferation and fibroblast recruitment was decreased in tumor foci while a higher number of apoptotic cells were observed. Finally, RNA levels for the inflammatory mediators COX-2, IFNγ, IL1β, IL6 and TNFα were reduced in total liver. In conclusion, OOS reduced the metastatic development of colorectal cancer to the liver by increasing apoptosis, and decreasing tumor cell proliferation and fibroblast recruitment in the tumor foci, as well as the expression of inflammatory mediators in total liver. These results point out OOS as a potential supplement to be applied as complementary therapy for the treatment of liver metastasis from colorectal cancer.

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

“…These studies also demonstrated that OOS provoked cleavage of caspase 3 both in vitro and in vivo, and giving support to the fact that OOS can trigger caspase-dependent cell death [72]. A similar increase in caspase 3 and the subsequent apoptotic cell death has also been described in metastatic liver lesions coming from colorectal carcinoma treated with OOS [68].…”

“…In a physiological in vivo context using mice and a multiplexed assay to measure a number of circulating cytokines, OOS significantly increased the amount of IL-6 [72]. In contrast, in a colorectal carcinoma model of metastasis to the liver, OOS treatment caused decrease in that cytokine in the liver tissue [68]. In that same study, OOS also reduced IFNα, TNFα, IL-1β, and COX2.…”

“…Metastatic spreading to the liver represents one of the major life-threatening morbidities of that disease. Using in vitro models of colorectal cancer, it was reported that OOS reduced cell viability of colorectal carcinoma cells [68]. In the in vivo model used to study the metastatic dissemination of tumor cells to the liver, OOS decreased the size of such metastatic lesions and increased apoptotic cell death within the tumors.…”

CBX8 and CD96 Are Important Prognostic Biomarkers of Colorectal Cancer

“…Variations of some muscle-specific molecules were also verified to affect the progression of CRC. For example, the muscle-specific miR-113b was down-regulated in CRC [ 28 ], and the expression of alpha smooth muscle actin (caspase-3 and Ki-67) can influence the effectiveness of Ocoxin ® oral solution in liver metastatic CRC [ 29 ]. All of those studies should provide valuable therapeutic targets for CRC.…”

Oncoxin‑Viusid^® may improve quality of life and survival in patients with hormone‑refractory prostate cancer undergoing onco‑specific treatments

“…The improvement in prostate symptoms suggested tumour reduction following combination treatment. In a preclinical study of colorectal cancer metastasis in the liver, it was demonstrated that Ocoxin oral solution slows down tumour growth (63). It may be used in combination with a standard therapy to potentiate antiproliferative action in acute myeloid leukaemia and lung cancer (64,65).…”