• Fatemeh Kalalinia

      Articles written in Journal of Biosciences

    • ABCG2 Inhibition as a Therapeutic Approach for Overcoming Multidrug Resistance in Cancer

      Maryam Hosseini Hasanabady Fatemeh Kalalinia

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      Breast cancer resistance protein (BCRP, ABCP or MXR) / ATP-binding cassette subfamily G member 2 (ABCG2) was characterized as a multidrug resistance efflux transporter in 1998. ABCG2 physiologically acts as a part of a self-defense mechanism for the organism; it enhances eliminating of toxic xenobiotic substances and harmful agents in the intestine, as well as through the blood-brain barrier and placental. ABCG2 recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and new targeted small therapeutic molecules in clinical usage. Development of ABCG2 inhibitors for clinical usage may allow increased penetration of therapeutic agents into sanctuary sites and increased their intestinal absorption. In this report, we review the mechanisms that modulate MDR mediated by the ABC transporter ABCG2 in normal and cancer cells by different levels including, epigenetic modifications, transcriptional, posttranscriptional, translation and posttranslational regulation. Some clinical applications of ABCG2 inhibitors, also is explained.

    • ABCG2 aptamer selectively delivers doxorubicin to drug-resistant breast cancer cells

      SHIRIN HASHEMITABAR REZVAN YAZDIAN-ROBATI MARYAM HASHEMI MOHAMMAD RAMEZANI KHALIL ABNOUS FATEMEH KALALINIA

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      Chemotherapy is the most widely used treatment for cancer therapy, but its efficacy is limited by the side effects of non-specificcytotoxic drugs. Ligand-based targeting drug-delivery system is a solution to circumvent this issue. In this study, an ABCG2aptamer–doxorubicin complex was prepared, and its efficacy in targeted drug delivery tomitoxantrone-resistance breast cancer cellline (MCF7/MX) was evaluated. The formation of aptamer–doxorubicin physical complex was analyzed by fluorometric analysis.The cytotoxicities of doxorubicin and aptamer–doxorubicin complex on MCF7 and MCF7/MX cell lines were evaluated by theMTT assay, and IC50 values were obtained. Cellular uptake of aptamer–doxorubicin complex was assessed by flow cytometrycellular uptake assay. Results: Fluorometric analysis of aptamer–doxorubicin showed 1–1.5 molar ratio of the drug to the aptamercould efficiently quenchDox fluorescence.MTTassay results showed that MCF7/MXcells were more resistant to doxorubicin thanMCF7 cells (IC50 : 3.172 ± 0.536 and 1.456 ± 0.154 lM, respectively). Flow cytometry andMTTassay results showed that theaptamer–doxorubicin complex could increase the uptake and cytotoxicity of doxorubicin inMCF7/MX cell line in comparison withfree doxorubicin, while the same treatments had no effect on IC50 of Dox on MCF7 cells. The results proposed that the ABCG2aptamer–drug complex can be effectively used for specific drug delivery to ABCG2-overexpressing cells.

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