Cancer Letters

Cancer Letters

Volume 268, Issue 2, 18 September 2008, Pages 348-359
Cancer Letters

Antioxidant potential by arabinoxylan rice bran, MGN-3/biobran, represents a mechanism for its oncostatic effect against murine solid Ehrlich carcinoma

https://doi.org/10.1016/j.canlet.2008.04.012Get rights and content

Abstract

We have recently examined the oncolytic effect of arabinoxylan rice bran, MGN-3/biobran, against solid Ehrlich carcinoma (SEC)-bearing mice via immune-modulation and apoptosis [N.K. Badr El-din, E. Noaman, M. Ghoneum, In vivo tumor inhibitory effects of nutritional rice bran supplement MGN-3/biobran on Ehrlich carcinoma-bearing mice, Nutr. Cancer 60 (2) (2008) 235–244]. In the present study, we examined the antioxidant system as another possible mechanism through which MGN-3 exerts its oncostatic potential. Female albino mice were inoculated intramuscularly in the right thigh with Ehrlich ascites carcinoma (EAC) cells. MGN-3 (25 mg/kg body weight) was injected intraperitoneally (i.p.) six times a week for 25 days into mice at either day 4 or day 11 post-EAC cell inoculation. Tumor growth, lipid peroxidation (LPx), glutathione (GSH) contents, the activity of the antioxidant scavenger enzymes, and alterations in gene expression were examined. MGN-3 efficiently suppressed the growth of tumors, which was associated with normalization of the LPx levels and augmentation of GSH contents. MGN-3 enhanced the activity of the endogenous antioxidant scavenging enzymes – superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione-S-transferase (GST) – in blood, liver, and tumor tissue. Similarly it up-regulated the expression of GPx, SOD1 and CAT mRNA in the liver. The effect of MGN-3 was more pronounced when treated early, at day 4 of tumor cell inoculation, as compared to later treatment at 11 days. In conclusion, MGN-3-induced oncostatic activity by modulating lipid peroxidation, augmenting the antioxidant defense system and protecting against oxidative stress.

Introduction

Antioxidants play an important role in inhibiting the activity of scavenging radicals, thus providing protection to humans against infection and degenerative diseases. The relationship between the antioxidant systems and growth of malignant cells is a commonly observed feature. Several studies have indicated that tumor growth can cause antioxidant disturbances in certain tissues of the tumor host [2], [3], [4]. One of the characteristics of tumor growth and invasion is the increased flux of oxy-radicals and loss of cellular redox homeostasis. Cancer cells can generate large amounts of hydrogen peroxide, which may contribute to their ability to mutate, damage normal tissues and invade other tissues. This suggests that there is a direct correlation between changes in the rate of cancer cell proliferation and changes in the antioxidant machinery; consistent with this, some anticancer agents can act as antioxidants [4], [5], [6].

Several biological response modifiers (BRMs) have been examined for anticancer activity with limited success due to toxicity. The need for a new cancer therapy with minimal or no side effects is greatly warranted. MGN-3 is a denatured hemicellulose, which is obtained by reacting rice bran hemicellulose with multiple carbohydrate hydrolyzing enzymes from the Shiitake mushroom. The main chemical structure of MGN-3 is an arabinoxylan with a xylose in its main chain and an arabinose polymer in its side chain [7]. Several reports have shown MGN-3 to be a potent biological response modifier (BRM) that activates the host immune response [1], [8], [9], [10], [11], [12]. In addition, MGN-3 was found to exhibit anticancer activity as exemplified by its ability to: (a) arrest the growth of a cutaneous squamous cell carcinoma (SCC13) cell line [13], (b) enhance yeast-induced apoptosis of cancer cells in vitro[14], (c) induce apoptosis of cancer cells in vivo[1], and (d) protect against severe loss of body weight in mice due to treatment with chemotherapeutic agents [15], [16].

In the model of solid Ehrlich carcinoma (SEC)-bearing mice, we observed abnormal antioxidant status [4], [5] and the ability of MGN-3 to induce a marked anti-neoplastic activity through immune-modulation and apoptosis [1]. Therefore, it was in our interests to examine whether MGN-3 might suppress SEC growth through the antioxidant system in vivo. We were encouraged to carry out this research based on an earlier study that shows that MGN-3 possesses potential active oxygen radical scavenging activity in vitro[17]. Additionally, we evaluated the effectiveness of early treatment of low dosage of MGN-3 (25 mg/kg BW) on tumor growth.

Section snippets

Mice

Adult female Swiss albino mice of about 8 weeks of age with an average body weight of 24 ± 2 g were used in this investigation. Mice were housed 5/cage and were allowed free access to standard laboratory cube pellets and water.

Tumor cell line, solid tumor production, and MGN-3

The murine Ehrlich ascites carcinoma (EAC) cells used in this study were originally obtained from the National Cancer Institute, Cairo University, Egypt, and maintained in vivo by weekly intraperitoneal passage of 2.5 × 106 cells in female Swiss albino mice.

Solid tumors were

Effect of MGN-3 treatment on tumor volume (TV) and tumor weight (TW)

Fig. 1A shows the antitumor activity of early (day 4) or late treatment (day 11) with MGN-3 against SEC tumor-bearing mice. Treatment with MGN-3 caused marked and progressive suppression of the tumor volume in both MGN-3 treated groups. However, the antitumor effect was more pronounced in the group treated with MGN-3 on day 4 as compared with treatment at day 11 post-tumor cell inoculation. The maximum tumor growth retardation on day 25 post-tumor cell inoculation was 54% and 24% (p < 0.01) for

Discussion

We have recently showed that MGN-3 (40 mg/kg body weight), when it is administered at day 8 and 11 post-tumor cell inoculation, exhibits anticancer activity against SEC bearing mice [1]. In this study, early administration of MGN-3 at day 4 post-tumor cell inoculation with a dose as low as 25 mg/kg BW to tumor-bearing mice showed a marked and progressive suppression of the tumor growth. This data suggests that the earlier MGN-3 is administered the greater its anticancer potential. The antitumor

Conclusions

In conclusion, the present study demonstrates that a challenge dose of 25 mg/kg BW of MGN-3 inhibited the development and growth of tumor, protected animals from body weight loss, decreased lipid peroxidation and augmented the endogenous antioxidant enzymes. The potential antioxidant and antitumor effects of MGN-3 were shown to be more pronounced when treated at day 4 post-tumor cell inoculation. Thus it appears that inclusion of MGN-3 in the diet may improve the antioxygenic potential and

Acknowledgements

We thank Daiwa Pharmaceuticals, Co. Ltd, Tokyo, Japan, for generously providing the MGN-3. The authors are also greatly indebted to the Rebecca Terra, UCLA, Department of Microbiology, Immunology and Molecular Genetics, for her careful revisions and helpful discussions.

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