A novel stealth liposomal topotecan with amlodipine: apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine thus leading to an enhanced antitumor activity in leukemia

Journal of Controlled Release : Official Journal of the Controlled Release Society
Xing LiQiang Zhang

Abstract

The objectives of the present study were to define whether amlodipine induces apoptosis and what mechanism is involved in the process in human resistant and non-resistant leukemia cells following co-administration of stealth liposomal topotecan with amlodipine, a novel antiresistant liposomes developed by our institution. In three leukemias, K562, HL-60, and multidrug resistant (MDR) HL-60, cytotoxicity of topotecan was potentiated by amlodipine, while topotecan alone was resistant to MDR HL-60 cells. In two selected K562 or MDR HL-60 cells, the apoptotic effects were increased by addition of amlodipine, showing a dose-dependent manner. The activities of caspase 3 and 7 (marked as caspase 3/7), and caspase 8 were significantly activated by topotecan with amlodipine co-treated as the stealth liposomes. The deletions of intracellular Ca2+ stores induced by amlodipine correlated with the activated activities of caspase 3/7, or 8, respectively. In xenograft model with MDR HL-60 in nude mice, antitumor activity of stealth liposomal topotecan with amlodipine was significantly enhanced as compared to that of stealth liposomal topotecan or topotecan alone. In conclusion, apoptotic effect is associated with deletion of intracellular Ca2...Continue Reading

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Citations

Jan 30, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Masayoshi AsaiHiroshi Watanabe
Oct 30, 2009·International Journal of Molecular Sciences·Kyung Taek OhEun Seong Lee
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Oct 6, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Xue YingQiang Zhang
Jun 6, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Xiang Rong SongYu Quan Wei
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Nov 9, 2016·Journal of Pharmaceutics·Muhammad Ali SherazIqbal Ahmad
Feb 12, 2019·Nutrition and Cancer·Sayantani DuttaC Anandharamakrishnan

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