2019 ; Vol.29-11: 1799~1805
|Author||Mili Joshi, Jong-Soo Choi, Jae-Won Park, Kyung-Oh Doh|
|Place of duty||Department of Physiology, College of Medicine, Yeungnam University, Daegu 42415 Republic of Korea.|
|Title||Combination of Doxorubicin with Gemcitabine-Incorporated GQuadruplex Aptamer Showed Synergistic and Selective Anticancer Effect in Breast Cancer Cells|
J. Microbiol. Biotechnol.2019 ;
|Abstract||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.|
|Key_word||G-Quadruplex aptamer, selective Anticancer Therapy, Doxorubicin, breast cancer, gemcitabine|
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