Vol 46, No 2 (2008)
Original paper
Submitted: 2011-12-19
Published online: 2008-06-04
Molecular basis of parthenolide-dependent proapoptotic activity in cancer cells.
Beata Pajak, Barbara Gajkowska, Arkadiusz Orzechowski
DOI: 10.2478/v10042-008-0019-2
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Folia Histochem Cytobiol 2008;46(2):129-135.
Vol 46, No 2 (2008)
ORIGINAL PAPERS
Submitted: 2011-12-19
Published online: 2008-06-04
Abstract
This review outlines the molecular events that accompany the anti-tumor action of parthenolide (PN). Parthenolide (PN) is naturally derived compound, isolated from plant Tanacetum parthenium. PN has been previously shown to withdraw cells from cell cycle or to promote cell differentiation, and finally to induce programmed cell death. Recent advances in molecular biology indicate that this sesquiterpene lactone might evoke the above-mentioned effects by indirect action on genes. PN was shown to inhibit NF-kappaB- and STATs-mediated antiapoptotic gene transcription. On one hand, the proapoptotic activity of PN includes stimulation of intrinsic apoptotic pathway with the higher level of intracellular ROS and modifications of Bcl-2 family proteins (conformational changes of Bak and Bax, Bid cleavage). On the other hand, PN amplifies the apoptotic signal through the sensitization of cancer cells to extrinsic apoptosis, induced by TNF-alpha. These effects are specific to tumor cells. Unique properties of PN make this agent a promising metabolic inhibitor to retard tumorigenesis and to suppress tumor growth.
Abstract
This review outlines the molecular events that accompany the anti-tumor action of parthenolide (PN). Parthenolide (PN) is naturally derived compound, isolated from plant Tanacetum parthenium. PN has been previously shown to withdraw cells from cell cycle or to promote cell differentiation, and finally to induce programmed cell death. Recent advances in molecular biology indicate that this sesquiterpene lactone might evoke the above-mentioned effects by indirect action on genes. PN was shown to inhibit NF-kappaB- and STATs-mediated antiapoptotic gene transcription. On one hand, the proapoptotic activity of PN includes stimulation of intrinsic apoptotic pathway with the higher level of intracellular ROS and modifications of Bcl-2 family proteins (conformational changes of Bak and Bax, Bid cleavage). On the other hand, PN amplifies the apoptotic signal through the sensitization of cancer cells to extrinsic apoptosis, induced by TNF-alpha. These effects are specific to tumor cells. Unique properties of PN make this agent a promising metabolic inhibitor to retard tumorigenesis and to suppress tumor growth.
Title
Molecular basis of parthenolide-dependent proapoptotic activity in cancer cells.
Journal
Folia Histochemica et Cytobiologica
Issue
Vol 46, No 2 (2008)
Article type
Original paper
Pages
129-135
Published online
2008-06-04
Page views
3615
Article views/downloads
3484
DOI
10.2478/v10042-008-0019-2
Bibliographic record
Folia Histochem Cytobiol 2008;46(2):129-135.
Authors
Beata Pajak
Barbara Gajkowska
Arkadiusz Orzechowski