Abstract

Breast cancer is the most common type of cancer in women worldwide and it is the second cause of cancer death after lung cancer. There have been many efforts in producing various pharmaceuticals for breast cancer treatment and among them Nanopharmaceutical Sciences have been extremely of high importance. All the drugs used to treat a cancer were usually shown unpleasant side effects. Chlorambucil is an older antineoplastic (anticancer) drug that is an alkylating agent with many known side effects for the patients. Recent findings have shown that the uptake of polyamine compounds such as amino acids (e.g. Methionine) in cancer cells is mostly increased. In this study a molecular antineoplastic conjugate, Chlorambucil-Methionine was developed and evaluated on the breast cancer MCF-7 cell line. For evaluation MTT assay, apoptosis assay and necrosis assay were employed but the mechanism of cell death or toxicity comparison were investigated by apoptosis-necrosis assay or abnormal toxicity test. Chlorambucil-Methionine as a targeted antineoplastic conjugate has shown higher antineoplastic properties and had not shown abnormal toxicity. The conjugate showed very good anticancer effects same as Chlorambucil but it had less toxicity in comparison with Chlorambucil. Apoptosis was the mechanism for most cell death in this study. Based on the results Chlorambucil-Methionine conjugate may be a better option than Chlorambucil alone for the treatment of breast cancer. Further study is recommended to confirm these findings in clinical practice.

Highlights

  • Breast cancer is the most common cancer in women worldwide

  • In this research we investigate the steps of synthesis of ChlorambucilMethionine conjugate, its purification, culture of MCF-7 cell line and some biological tests in order to verify the effectiveness and toxic level of the mentioned conjugate

  • MCF-7 cell line was placed in 96 wells plate and exposed to Chlorambucil-Methionine conjugate

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Summary

Introduction

Breast cancer is the most common cancer in women worldwide. Breast cancer is second only to lung cancer in cancer deaths among women worldwide [1,2,3,4,5].Many investigators have tried to develop targeted drug delivery via specific molecules to tumors. Breast cancer is the most common cancer in women worldwide. Breast cancer is second only to lung cancer in cancer deaths among women worldwide [1,2,3,4,5]. A certain amount of medicine can be delivered selectively to tumor cells with toxicity. In this method we used molecules that exist in cancerous tissues, there is an affinity by these tissues to absorb them [6,7,8]. Transfer of amino acids is necessary for growth and differentiation of normal and the transferred cells. Methionine (Met) is one of the essential and nonpolar amino acids. In 2005, it was proven that there is an increased rate of transfer of certain essential amino acids in tumor cells; inhibition of the carriers of these amino acids can suppress the tumor as well as the growth of tumor cells [9]

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