Anticancer activity of Egyptian marine alga Ulva rigida

Introduction

Marine organism–derived medicines have several features that make them particularly suitable for consideration as sources of anti-neoplastic agents. For example, the vast majority of marine invertebrates have only primitive immune systems, and thus, they produce toxic substances as a form of defense; these substances would be expected to have high potency and low solubility, given that they are immediately and tremendously diluted by water. Therefore, an increasing number of compounds derived from sponges, algae, mollusks, and other marine organisms are being tested for their therapeutic effects against cancer and other diseases in clinical and preclinical trials. The objectives are to investigate the cytotoxic activity of different extracts of four Egyptian marine algae on the Ehrlich ascites carcinoma (EAC) cell line in vitro. Further study was conducted in vivo to evaluate the antitumor activity of different extract of Ulva rigida against solid tumor induced in female mice by EAC cell line.

Methods

Four marine algae were from Abu-Qir gulf, Alexandria, Egypt. These algae were identified as Ulva rigida, Enteromorpha clathrata, Jania adherens and Corallina elongata . Algae extracts were prepared and lyophilized. The cytotoxic activity of these algae extracts was determined in vitro against Ehrlich ascites carcinoma (EAC) cell line. The antitumor efficacy of Ulva rigida extracts was investigated in vivo against solid tumor-bearing mice induced by EAC cell line. Solid tumor was induced in Albino mice, except normal control group; by injecting 2×10⁵ EAC cells subcutaneously. Twenty-four hours post EAC inoculation, 0.1 ml of tested extracts was injected subcutaneously for 3 consecutive days. Lipid peroxidation, antioxidant level and VEGF were assayed.

Results

Varied inhibitory effects of algal extracts on the proliferation of EAC cell line in vitro were shown. Moreover, Ulva rigida exhibited the most potent antiproliferative effect on EAC cell line in a dose-dependent manner. In vivo results showed that methanol extract of Ulva rigida inhibits the growth of solid tumor induced in mice by EAC cell line. Treatment with methanol or chloroform extract of Ulva rigida resulted in significant reductions in the level of lipid peroxidation. The maximal protective effects against hepatic lipid peroxidation (64.8 ± 4.5 and 69.6 ± 13.3 nmol/g of tissue) were observed when solid tumor bearing mice treated with 80 and 100 μg/ml of methanol extracts of Ulva rigida, respectively. The maximal augmentation in antioxidant enzymes activity was observed at the same concentrations of Ulva rigida in SOD and CAT activities; these increments are associated with the reduction in tumor volume revealing the antitumor activity of Ulva rigida. In addition, vascular endothelial growth factor was maximally reduced in tumor-bearing mice treated with these concentrations of Ulva rigida alga. This finding revealed the antiangiogeneic role of Ulva rigida.

In conclusion, this study shed light on the antitumor activity of some marine algae grown in Egyptian coast. This study showed that Ulva rigida exerts its antitumor activity through augmentation of antioxidant status and antiangiogeneic efficacy.