Journal of Microbiology and Biotechnology

  • 제29권11호
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  • Pages.1799-1805
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  • 2019
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  • 1017-7825(pISSN)
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  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
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Combination of Doxorubicin with Gemcitabine-Incorporated G-Quadruplex Aptamer Showed Synergistic and Selective Anticancer Effect in Breast Cancer Cells

  • Joshi, Mili (Department of Physiology, College of Medicine, Yeungnam University) ;
  • Choi, Jong-Soo (Department of Physiology, College of Medicine, Yeungnam University) ;
  • Park, Jae-Won (Department of Physiology, College of Medicine, Yeungnam University) ;
  • Doh, Kyung-Oh (Department of Physiology, College of Medicine, Yeungnam University)
  • 투고 : 2019.07.12
  • 심사 : 2019.09.03
  • 발행 : 2019.11.28
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초록

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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  1. NLRP3 augmented resistance to gemcitabine in triple-negative breast cancer cells via EMT/IL-1β/Wnt/β-catenin signaling pathway vol.40, pp.7, 2019, https://doi.org/10.1042/bsr20200730
  2. G-Quadruplex-Based Drug Delivery Systems for Cancer Therapy vol.14, pp.7, 2019, https://doi.org/10.3390/ph14070671