Antineoplastic activities of MT81 and its structural analogue in Ehrlich ascites carcinoma-bearing Swiss Albino mice.

Sujata Maiti Choudhury,Malaya Gupta,Upal Kanti Majumder

doi:10.4161/oxim.3.1.10495

Sujata Maiti Choudhury, Malaya Gupta + Show 1 more

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https://doi.org/10.4161/oxim.3.1.10495

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Abstract

Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin,a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81)] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC) tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p.) at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight) for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST), increased life span (ILS), tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA) and reduced glutathione (GSH) content, and by the activity of superoxide dismutase (SOD) and catalase (CAT). MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

Highlights

Cancer is one of the most dreaded diseases of the 20th century
From literature it is revealed that many natural products are available as chemo-preventive agents against commonly occurring cancer types
The in vitro cytotoxicity of MT81 and its structural analogue towards Ehrlich ascites carcinoma (EAC) cells showed that the IC50 of MT81, Aa-MT81 were 17 μg, 22 μg/ml respectively

Summary

Introduction

Cancer is one of the most dreaded diseases of the 20th century. It is the single most common cause of deaths and spreading further with continuance in 21st century in both developed and developing countries.[1,2] Statistics show that men are largely plagued by lung, colon, rectal and prostate cancer, while women increasing suffer from breast, stomach, colon and rectal cancer. From literature it is revealed that many natural products are available as chemo-preventive agents against commonly occurring cancer types. There is continuing need for identification, characterization and development of new chemo-preventive agents from enormous pool of synthetic, biological and natural products. About 60% of currently used anticancer agents are obtained from natural sources, including plants, marine organisms and microorganisms. Mycophenolic acid,[3] penicillic acid,[4]

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