51. High in vitro and in vivo antitumor activities of luminecent platinum(II) complexes with jatrorrhizine derivatives
- Author
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Xiao-Ling Huang, Bi-Qun Zou, Zhen-Feng Wang, Ming-Xiong Tan, Shu-Long Wang, Qi-Pin Qin, Ye Zhang, and Hong Liang
- Subjects
Male ,Jatrorrhizine ,Telomerase ,Berberine ,Organoplatinum Compounds ,Cell Survival ,Stereochemistry ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,urologic and male genital diseases ,01 natural sciences ,HeLa ,03 medical and health sciences ,chemistry.chemical_compound ,In vivo ,Drug Discovery ,medicine ,Animals ,Humans ,Fluorescent Dyes ,Platinum ,030304 developmental biology ,Pharmacology ,Cisplatin ,Mice, Inbred BALB C ,0303 health sciences ,biology ,010405 organic chemistry ,Ligand ,Optical Imaging ,Organic Chemistry ,General Medicine ,biology.organism_classification ,Mitochondria ,0104 chemical sciences ,chemistry ,Cancer cell ,DNA Damage ,HeLa Cells ,medicine.drug - Abstract
Two highly active anticancer Pt(II) complexes, [Pt(Jat1)Cl]Cl (Pt1) and [Pt(Jat2)Cl]Cl (Pt2), containing jatrorrhizine derivative ligands (Jat1 and Jat2) are described. Cell intake study showed high accumulation in cell nuclear fraction. Pt1 and Pt2 exhibited high selectivity for HeLa cancer cells (IC50 = 15.01 ± 1.05 nM and 1.00 ± 0.17 nM) comparing with HL-7702 normal cells (IC50 > 150 μM), by targeting p53 and telomerase. Pt2 containing Jat2 ligand was more potent and showed high selectivity for telomerase. It also caused mitochondria and DNA damage, sub-G1 phase arrest, and a high rate of cell apoptosis at the low dose of 1.00 nM. The HeLa tumor inhibition rate (TIR) of Pt2 was 48.8%, which was even higher than cisplatin (35.2%). In addition, Pt2 displayed green luminescent property and potent telomerase inhibition. Our findings demonstrated the promising development of platinum(II) complexes containing jatrorrhizine derivatives as novel Pt-based anti-cancer agents.
- Published
- 2019
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