Pterostilbene-induced tumor cytotoxicity: a lysosomal membrane permeabilization-dependent mechanism
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Pterostilbene-induced tumor cytotoxicity : a lysosomal membrane permeabilization-dependent mechanism. / Mena, Salvador; Rodríguez, María L; Ponsoda, Xavier; Estrela, José M; Jaattela, Marja; Ortega, Angel L.
I: PLOS ONE, Bind 7, Nr. 9, 2012, s. e44524.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Pterostilbene-induced tumor cytotoxicity
T2 - a lysosomal membrane permeabilization-dependent mechanism
AU - Mena, Salvador
AU - Rodríguez, María L
AU - Ponsoda, Xavier
AU - Estrela, José M
AU - Jaattela, Marja
AU - Ortega, Angel L
PY - 2012
Y1 - 2012
N2 - The phenolic phytoalexin resveratrol is well known for its health-promoting and anticancer properties. Its potential benefits are, however, limited due to its low bioavailability. Pterostilbene, a natural dimethoxylated analog of resveratrol, presents higher anticancer activity than resveratrol. The mechanisms by which this polyphenol acts against cancer cells are, however, unclear. Here, we show that pterostilbene effectively inhibits cancer cell growth and stimulates apoptosis and autophagosome accumulation in cancer cells of various origins. However, these mechanisms are not determinant in cell demise. Pterostilbene promotes cancer cell death via a mechanism involving lysosomal membrane permeabilization. Different grades of susceptibility were observed among the different cancer cells depending on their lysosomal heat shock protein 70 (HSP70) content, a known stabilizer of lysosomal membranes. A375 melanoma and A549 lung cancer cells with low levels of HSP70 showed high susceptibility to pterostilbene, whereas HT29 colon and MCF7 breast cancer cells with higher levels of HSP70 were more resistant. Inhibition of HSP70 expression increased susceptibility of HT29 colon and MCF7 breast cancer cells to pterostilbene. Our data indicate that lysosomal membrane permeabilization is the main cell death pathway triggered by pterostilbene.
AB - The phenolic phytoalexin resveratrol is well known for its health-promoting and anticancer properties. Its potential benefits are, however, limited due to its low bioavailability. Pterostilbene, a natural dimethoxylated analog of resveratrol, presents higher anticancer activity than resveratrol. The mechanisms by which this polyphenol acts against cancer cells are, however, unclear. Here, we show that pterostilbene effectively inhibits cancer cell growth and stimulates apoptosis and autophagosome accumulation in cancer cells of various origins. However, these mechanisms are not determinant in cell demise. Pterostilbene promotes cancer cell death via a mechanism involving lysosomal membrane permeabilization. Different grades of susceptibility were observed among the different cancer cells depending on their lysosomal heat shock protein 70 (HSP70) content, a known stabilizer of lysosomal membranes. A375 melanoma and A549 lung cancer cells with low levels of HSP70 showed high susceptibility to pterostilbene, whereas HT29 colon and MCF7 breast cancer cells with higher levels of HSP70 were more resistant. Inhibition of HSP70 expression increased susceptibility of HT29 colon and MCF7 breast cancer cells to pterostilbene. Our data indicate that lysosomal membrane permeabilization is the main cell death pathway triggered by pterostilbene.
KW - Antineoplastic Agents
KW - Apoptosis
KW - Autophagy
KW - Caspases
KW - Cell Death
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Dose-Response Relationship, Drug
KW - Flow Cytometry
KW - HSP70 Heat-Shock Proteins
KW - Humans
KW - Inhibitory Concentration 50
KW - L-Lactate Dehydrogenase
KW - Lysosomes
KW - Microscopy, Confocal
KW - Necrosis
KW - Neoplasms
KW - Permeability
KW - Phagosomes
KW - Stilbenes
U2 - 10.1371/journal.pone.0044524
DO - 10.1371/journal.pone.0044524
M3 - Journal article
C2 - 22957077
VL - 7
SP - e44524
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 9
ER -
ID: 47714842