Molecular Chlorambucil-Methionine Conjugate: Novel Anti-cancer Agent against Breast MCF-7 Cell Model

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.

Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

“…It may be concluded that Met may be used as a selective target for detection of tumor cells by Met-dependent phenotype. Therefore, Met as a targeting agent has been conjugated with some drug and imaging delivery systems for cancer therapy and tumor molecular imaging 19–21…”

Chlorambucil Encapsulation into PLGA Nanoparticles and Cytotoxic Effects in Breast Cancer Cell

“…These analogs showed significant anticancer activities compare to Chlorambucil. Also Omoomi [15] show the production of a new anticancer conjugate of Chlorambucil-Methionine which is highly effective, and has selective targeting features, as well as the ability to prevent the growth of the breast cancer MCF-7 cell line. Millard and coworkers [16] synthetized Mito-Chlor, a triphenylphosphonium derivative of the CHB which selectively targeting nitrogen mustards to cancer cell mitochondria based on mitochondrial membrane potential.…”

Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH2 Core and Evaluation of Their Anticancer Activity

“…The chemotherapeutic drug chlorambucil (CLB) is a nitrogen mustard derivative used in the treatment of some types of cancer, e.g., Hodgkin and non-Hodgkin lymphoma, as well as chronic lymphocytic leukemia [ 1 , 2 , 3 , 4 ]. The anticancer activity of CLB is based on its alkylation properties that damages the DNA and interferes with its replication.…”