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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2006-7-17
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pubmed:abstractText |
The effect of the carcinogen safrole on intracellular Ca2+ movement has not been explored in osteoblast-like cells. This study examined whether safrole could alter Ca2+ handling and viability in MG63 human osteosarcoma cells. Cytosolic free Ca2+ levels ([Ca2+]i) in populations of cells were measured using fura-2 as a fluorescent Ca2+ probe. Safrole at concentrations above 130 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 450 microM. The Ca2+ signal was reduced by 30% by removing extracellular Ca2+. Addition of Ca2+ after safrole had depleted intracellular Ca2+ induced Ca2+ influx, suggesting that safrole caused Ca2+ entry. In Ca2+-free medium, after pretreatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) failed to release more Ca2+; and pretreatment with thapsigargin inhibited most of the safrole-induced [Ca2+]i increases. Inhibition of phospholipase C with U73122 did not affect safrole-induced Ca2+ release; whereas activation of protein kinase C with phorbol ester enhanced safrole-induced [Ca2+]i increase. Trypan exclusion assays revealed that incubation with 65 microM safrole for 30 min did not kill cells, but incubation with 650 microM safrole for 10-30 min nearly killed all cells. Flow cytometry demonstrated that safrole evoked apoptosis in a concentration-dependent manner. Safrole-induced cytotoxicity was not reversed by chelation of Ca2+ with BAPTA. Collectively, the data suggest that in MG63 cells, safrole induced a [Ca2+]i increase by causing Ca2+ release mainly from the endoplasmic reticulum in a phospholipase C-independent manner. The safrole response involved Ca2+ influx and is modulated by protein kinase C. Furthermore, safrole can cause apoptosis in a Ca2+-independent manner.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/1,2-bis(2-aminophenoxy)ethane-N,N,N'...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/Chelating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Fura-2,
http://linkedlifedata.com/resource/pubmed/chemical/Phorbol Esters,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Safrole,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/phorbol-12-myristate
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1043-6618
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pubmed:author |
pubmed-author:ChangHong-TaiHT,
pubmed-author:ChenI-ShuIS,
pubmed-author:ChenJin-ShyrJS,
pubmed-author:ChenWei-ChuanWC,
pubmed-author:ChengHe-HsiungHH,
pubmed-author:HsuShu-ShongSS,
pubmed-author:HuangChun-JenCJ,
pubmed-author:HuangJong-KhingJK,
pubmed-author:JanChung-RenCR,
pubmed-author:LinHsueh-ChiHC,
pubmed-author:LiuShiuh-InnSI,
pubmed-author:LuYih-ChauYC
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pubmed:issnType |
Print
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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 |
103-10
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16621588-Calcium,
pubmed-meshheading:16621588-Calcium Channel Blockers,
pubmed-meshheading:16621588-Calcium Signaling,
pubmed-meshheading:16621588-Carcinogens,
pubmed-meshheading:16621588-Cell Death,
pubmed-meshheading:16621588-Cell Line, Tumor,
pubmed-meshheading:16621588-Cell Survival,
pubmed-meshheading:16621588-Chelating Agents,
pubmed-meshheading:16621588-Dose-Response Relationship, Drug,
pubmed-meshheading:16621588-Egtazic Acid,
pubmed-meshheading:16621588-Endoplasmic Reticulum,
pubmed-meshheading:16621588-Fluorescent Dyes,
pubmed-meshheading:16621588-Fura-2,
pubmed-meshheading:16621588-Humans,
pubmed-meshheading:16621588-Osteosarcoma,
pubmed-meshheading:16621588-Phorbol Esters,
pubmed-meshheading:16621588-Protein Kinase C,
pubmed-meshheading:16621588-Safrole,
pubmed-meshheading:16621588-Spectrometry, Fluorescence,
pubmed-meshheading:16621588-Thapsigargin,
pubmed-meshheading:16621588-Time Factors
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pubmed:year |
2006
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pubmed:articleTitle |
Safrole-induced cellular Ca2+ increases and death in human osteosarcoma cells.
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pubmed:affiliation |
Department of Physical Medicine and Rehabilitation, St. Joseph Hospital, Kaohsiung 802, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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