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Glioblastoma cell death induced by asiatic acid

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Abstract

Asiatic acid (AA), a triterpene, is known to be cytotoxic to several tumor cell lines. AA induces dose- and time-dependent cell death in U-87 MG human glioblastoma. This cell death occurs via both apoptosis and necrosis. The effect of AA may be cell type-specific as AA-induced cell death was mainly apoptotic in colon cancer RKO cells. AA-induced glioblastoma cell death is associated with decreased mitochondrial membrane potential, activation of caspase-9 and -3, and increased intracellular free Ca2+. Although treatment of glioblastoma cells with the caspase inhibitor zVAD-fmk completely abolished AA-induced caspase activation, it did not significantly block AA-induced cell death. AA-induced cell death was significantly prevented by an intracellular Ca2+ inhibitor, BAPTA/AM. Taken together, these results indicate that AA induces cell death by both apoptosis and necrosis, with Ca2+-mediated necrotic cell death predominating.

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Abbreviations

Δψm :

mitochondrial transmembrane potential

AA:

asiatic acid

AMC:

7-amino-4-methylcoumarin

DEVD-AMC:

N-acetyl-Asp-Glu-Val-Asp-7-amino-4-methylcoumarin

DiOC6(3):

3,3′-dihexyloxacarbocyanide iodide

LDH:

lactate dehydrogenase

LEHD-AMC:

N-acetyl-Leu-Glu-His-Asp-AMC

PARP:

poly(ADP-ribose)-polymerase

PCD:

programmed cell death

PS:

phosphatidylserine

S-LLVY-AMC:

succinyl-Leu-Leu-Val-Tyr-AMC

STS:

staurosporine

zVAD-fmk:

benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone

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Authors and Affiliations

  1. Biomaterials Science and Engineering Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    C. W. Cho, D. S. Choi & C. Rha

  2. School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea

    C. W. Cho & C. W. Kim

  3. Eutropics Pharmaceuticals Inc., Dorchester, Massachusetts, USA

    M. H. Cardone

  4. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    A. J. Sinskey

  5. Biomaterials Science and Engineering Laboratory, Massachusetts Institute of Technology, 56–265, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA

    C. Rha

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  1. C. W. Cho
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  2. D. S. Choi
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  3. M. H. Cardone
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  4. C. W. Kim
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  5. A. J. Sinskey
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  6. C. Rha
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Correspondence to C. Rha.

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Cho, C.W., Choi, D.S., Cardone, M.H. et al. Glioblastoma cell death induced by asiatic acid. Cell Biol Toxicol 22, 393–408 (2006). https://doi.org/10.1007/s10565-006-0104-2

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  • DOI: https://doi.org/10.1007/s10565-006-0104-2

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