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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2011-4-7
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pubmed:abstractText |
Haloperidol (HP), a neuroleptic drug, shows high affinity toward ? receptors (SR). HP and reduced-HP at higher concentration were known to induce apoptosis in SR-overexpressing carcinomas and melanomas. Herein, we report the development of cationic lipid-conjugated haloperidol as a new class of anticancer therapeutics. In comparison to HP, the C-8 carbon chain analogue (HP-C8) showed significantly high, SR-assisted antiproliferative activity against cancer cells via caspase-3-mediated apoptosis and down-regulation of pAkt. Moreover, melanoma tumor aggressiveness in HP-C8-treated mice was significantly lower than that in HP-treated mice. HP-C8 simultaneously reduced Akt-protein level and increased Bax/Bcl-2 ratio in vascular endothelial cells, thereby indicating a possible protein kinase down-regulatory and apoptosis inducing role in tumor-associated vascular cells. In conclusion, we developed ? receptor-targeting cationic lipid-modified HP derivatives as a promising class of anticancer therapeutic that concurrently affects cancer and tumor environment associated angiogenic vascular cells through induction of apoptosis and Akt protein down-regulation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1520-4804
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
54
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2378-90
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pubmed:meshHeading |
pubmed-meshheading:21391684-Animals,
pubmed-meshheading:21391684-Antineoplastic Agents,
pubmed-meshheading:21391684-Apoptosis,
pubmed-meshheading:21391684-COS Cells,
pubmed-meshheading:21391684-Cell Line, Tumor,
pubmed-meshheading:21391684-Cell Proliferation,
pubmed-meshheading:21391684-Cercopithecus aethiops,
pubmed-meshheading:21391684-Drug Discovery,
pubmed-meshheading:21391684-Endothelium, Vascular,
pubmed-meshheading:21391684-Gene Knockdown Techniques,
pubmed-meshheading:21391684-Haloperidol,
pubmed-meshheading:21391684-Humans,
pubmed-meshheading:21391684-Lipids,
pubmed-meshheading:21391684-Male,
pubmed-meshheading:21391684-Mice,
pubmed-meshheading:21391684-Phosphoproteins,
pubmed-meshheading:21391684-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:21391684-RNA, Small Interfering,
pubmed-meshheading:21391684-Receptors, sigma,
pubmed-meshheading:21391684-Signal Transduction,
pubmed-meshheading:21391684-Structure-Activity Relationship
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pubmed:year |
2011
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pubmed:articleTitle |
Structure-activity study to develop cationic lipid-conjugated haloperidol derivatives as a new class of anticancer therapeutics.
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pubmed:affiliation |
Division of Lipid Science and Technology, Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh 500007, India.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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