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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

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Title: 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
Authors: Li, Xing1, Ruan, Guo-Rui2, Lu, Wan-Liang1 luwl@bjmu.edu.cn, Hong, Hai-Yan3, Liang, Gong-Wen1, Zhang, Yu-Teng1, Liu, Yang1, Long, Chuan3, Ma, Xi4, Yuan, Lan1, Wang, Jian-Cheng1, Zhang, Xuan1, Zhang, Qiang1
Source: Journal of Controlled Release. May2006, Vol. 112 Issue 2, p186-198. 13p.
Subjects: Calcium antagonists, Liposomes, Apoptosis, Leukemia
Abstract: 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 amolodipne, 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+ by amlodipine through activation of caspase 8 and then 3/7 activities. The enhanced antitumor activities by stealth liposomal topotecan with amlodipine are mainly due to the potentiating apoptotic effect and reversing the resistance by amlodipine. Stealth liposomal encapsulation of anticancer agent with a modulator may provide a novel strategy for improving the chemotherapeutic effects. [Copyright &y& Elsevier]
Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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Header DbId: egs
DbLabel: Engineering Source
An: 20621330
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
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  Label: Title
  Group: Ti
  Data: A novel stealth liposomal topotecan with amlodipine: Apoptotic effect is associated with deletion of intracellular Ca<superscript>2+</superscript> by amlodipine thus leading to an enhanced antitumor activity in leukemia
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  Data: <searchLink fieldCode="AR" term="%22Li%2C+Xing%22">Li, Xing</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Ruan%2C+Guo-Rui%22">Ruan, Guo-Rui</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Lu%2C+Wan-Liang%22">Lu, Wan-Liang</searchLink><relatesTo>1</relatesTo><i> luwl@bjmu.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Hong%2C+Hai-Yan%22">Hong, Hai-Yan</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Liang%2C+Gong-Wen%22">Liang, Gong-Wen</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Yu-Teng%22">Zhang, Yu-Teng</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Liu%2C+Yang%22">Liu, Yang</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Long%2C+Chuan%22">Long, Chuan</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Ma%2C+Xi%22">Ma, Xi</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Yuan%2C+Lan%22">Yuan, Lan</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Wang%2C+Jian-Cheng%22">Wang, Jian-Cheng</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Xuan%22">Zhang, Xuan</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Qiang%22">Zhang, Qiang</searchLink><relatesTo>1</relatesTo>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Controlled+Release%22">Journal of Controlled Release</searchLink>. May2006, Vol. 112 Issue 2, p186-198. 13p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Calcium+antagonists%22">Calcium antagonists</searchLink><br /><searchLink fieldCode="DE" term="%22Liposomes%22">Liposomes</searchLink><br /><searchLink fieldCode="DE" term="%22Apoptosis%22">Apoptosis</searchLink><br /><searchLink fieldCode="DE" term="%22Leukemia%22">Leukemia</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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 amolodipne, 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+ by amlodipine through activation of caspase 8 and then 3/7 activities. The enhanced antitumor activities by stealth liposomal topotecan with amlodipine are mainly due to the potentiating apoptotic effect and reversing the resistance by amlodipine. Stealth liposomal encapsulation of anticancer agent with a modulator may provide a novel strategy for improving the chemotherapeutic effects. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1016/j.jconrel.2006.01.007
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      – Code: eng
        Text: English
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      Pagination:
        PageCount: 13
        StartPage: 186
    Subjects:
      – SubjectFull: Calcium antagonists
        Type: general
      – SubjectFull: Liposomes
        Type: general
      – SubjectFull: Apoptosis
        Type: general
      – SubjectFull: Leukemia
        Type: general
    Titles:
      – TitleFull: 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
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              M: 05
              Text: May2006
              Type: published
              Y: 2006
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