Abstract

Earlier reports indicated that Bovine Cartilage (BC) had anti-tumor effects but only a few in vitro and in vivo investigations were conducted to assess its mechanism of action. The aim of this study was to investigate some of the proposed mechanisms of action of BC on mouse melanoma cells both in vitro and in vivo and to determine if its effect on tumor cells is selective. One hundred and ten mice were divided into 5 groups and received Intraperitoneal (IP) injections of melanoma cells followed by treatment with BC using different routes of administration. Following a daily treatment period of 16 days, serum levels of VEGF and IL-12 were determined by ELISA at 2, 4 and 6 h after the last treatment dose. Additionally, 10 mice from each group were monitored for survival for 20 days post-last treatment. Moreover, melanoma and mouse mononuclear cells were incubated separately with increasing BC concentrations for 48 h and percent viability was determined. A significant decrease in the serum levels of VEGF and significant increase in the serum levels of IL-12 were observed in the groups treated with BC. Moreover 20% survival rate was noted in the group treated with BC both orally and IP, whereas 10% survival was noted in the groups given BC either IP or orally. In vitro, total eradication of melanoma cells was observed with 1000 μg mL-1 of BC. BC was not toxic to mouse mononuclear cells. The in vivo anti-tumor effect of BC was best observed when combined IP and oral doses were given and it appears that two of its actions are by activating macrophages as indicated by increases in IL-12 levels and blocking angiogenesis as indicated by decreases in VEGF levels. Finally BC showed selective toxicity against melanoma cells.

Highlights

  • The use of Bovine Cartilage (BC) as a treatment for several medical conditions has been around for more than 40 years

  • Total eradication of melanoma cells was obtained in the wells treated with 500 μL of 1000 and 5000 μg mL−1 of BC (Fig. 5)

  • When compared to the control well, the viability of mouse mononuclear cells remained relatively stable throughout the first four BC concentrations (5, 10, 100 and 1000 μg mL−1) after 48 h; a slight insignificant decrease was seen with the highest BC concentration which is 5000 μg mL−1 (88% survival rate) (Fig. 5)

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Summary

Introduction

The use of Bovine Cartilage (BC) as a treatment for several medical conditions has been around for more than 40 years. Dr Prudden was the first to assess the ability of BC to accelerate healing in experimental wounds (Prudden et al, 1975; Takayuki, 1960; Prudden et al, 1962). The obtained positive results drove Prudden to test the accelerating effect of BC on several different laboratory animals and on humans, where in both cases results were significant (Prudden et al, 1964; Prudden, 1964; Prudden and Allen, 1965). A study conducted by (Houck et al, 1961) showed that BC had potent anti-inflammatory activity which was further emphasized, when a patient with psoriasis and a non-healing ulcer markedly improved upon BC treatment. The initial decision to test BC in the clinical treatment of cancer was based on its efficiency in the treatment of psoriasis, on its record of being non-toxic and on its ability to cure a patient’s ulcerated breast cancer. There were some significant decreases in a wide variety of intractable malignancies and all the patients except one survived longer than the time predicted by their clinicians (Prudden, 1985)

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