Combination of Doxorubicin with Gemcitabine-Incorporated GQuadruplex Aptamer Showed Synergistic and Selective Anticancer Effect in Breast Cancer Cells

吉西他滨 阿霉素 适体 结合 乳腺癌 细胞毒性 核仁素 心脏毒性 化学 癌症研究 癌症 药理学 癌细胞 化疗 医学 生物化学 生物 毒性 体外 分子生物学 内科学 细胞质 有机化学 核仁 数学分析 数学
作者
Mili Joshi,Jong‐Soo Choi,Jae-Won Park,Kyung-Oh Doh
出处
期刊:Journal of Microbiology and Biotechnology [Journal of Microbiology and Biotechnology]
卷期号:29 (11): 1799-1805 被引量:8
标识
DOI:10.4014/jmb.1907.07029
摘要

Doxorubicin (DOX) is one of the most effective anticancer agents used for the treatment of multiple cancers; however, its use is limited by its short half-life and adverse drug reactions, especially cardiotoxicity. In this study, we found that the conjugate of DOX with APTA12 (Gemcitabine incorporated G-quadruplex aptamer) was significantly more cancer selective and cytotoxic than DOX. The conjugate had an affinity for nucleolin, with higher uptake and retention into the cancer cells than those of DOX. Further, it was localized to the nucleus, which is the target site of DOX. Owing to its mechanism of action, DOX has the ability to intercalate into the nucleotides thus making it a suitable drug to form a conjugate with cancer selective aptamers such as APTA12. The conjugation can lead to selectively accumulate in the cancer cells thus decreasing its potential nonspecific as well as cardiotoxic side effects. The aim of this study was to prepare a conjugate of DOX with APTA12 and assess the chemotherapeutic properties of the conjugate specific to cancer cells. The DOX-APTA12 conjugate was prepared by incubation and its cytotoxicity in MCF-10A (non-cancerous mammary cells) and MDA-MB-231 (breast cancer cells) was assessed. The results indicate that DOX-APTA12 conjugate is a potential option for chemotherapy especially for nucleolin expressing breast cancer with reduced doxorubicin associated side effects.
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