A potent aminonaphthalimide platinum(IV) complex with effective antitumor activities in vitro and in vivo displaying dual DNA damage effects on tumor cells |
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| Authors: | Qingpeng Wang Yan Chen Guoshuai Li Yanna Zhao Zhifang Liu Ruiyan Zhang Min Liu Dacheng Li Jun Han |
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| Affiliation: | 1. Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China;2. State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, PR China;3. Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology, Liaocheng University, Liaocheng 252059, PR China |
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| Abstract: | A new aminonaphthalimide platinum(IV) complex was developed by incorporating aminonaphthalimide, a DNA intercalator, into the platinum(IV) system. This complex displayed potent antitumor activities against all tested tumor cell lines in vitro and showed great potential in overcoming drug resistance of cisplatin. Moreover, it remarkably inhibited the growth of CT26 xenografts in BALB/c mice without severe side effects in vivo. Then, the compound exhibited a dual DNA damage antitumor mechanism that it could interact with DNA in tetravalent form via the naphthalimide group to cause DNA lesion, and the further liberation of platinum(II) complex after reduction would induce remarkable secondary damage to DNA. Meanwhile, it caused cell apoptosis through an intrinsic apoptosis pathway by up-regulating the expression of caspase 3 and caspase 9. |
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| Keywords: | Corresponding authors at: Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, PR China (D. Li). Antitumor Platinum Prodrug DNA damage Naphthalimide |
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