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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.4
- 수록면
- 327 - 335 (9page)
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Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF- 10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factorerythroid- 2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF- 10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells.
Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species.
Instead, piperlongumine, which bears electrophilic , -unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, whichaccounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine.
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참고문헌 (32)
참고문헌 신청
Alam, J. / 1999 / Nrf2, a Cap’n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene / J. Biol.Chem 274:26071~26078
배진범 / 2013 / Berberine Protects 6-Hydroxydopamine-Induced Human Dopaminergic Neuronal Cell Death through the Induction of Heme Oxygenase-1 / Molecules and Cells 35(2):151~157
Bauer, M. / 2002 / Heme oxygenase-1 : Redox regulation and role in the hepatic response to oxidative stress / Antioxid. Redox Signal 4:749~758
Becker, J. C. / 2007 / Colonic expression of heme oxygenase-1 is associated with a better long-term survival in patients with colorectal cancer / Scand. J. Gastroenterol 42:852~858
Bezerra, D. P. / 2012 / Overview of the therapeutic potential of piplartine(piperlongumine) / Eur. J. Pharm. S 48:453~463
배진범 / 2013 / Berberine Protects 6-Hydroxydopamine-Induced Human Dopaminergic Neuronal Cell Death through the Induction of Heme Oxygenase-1 / Molecules and Cells 35(2):151~157
Bauer, M. / 2002 / Heme oxygenase-1 : Redox regulation and role in the hepatic response to oxidative stress / Antioxid. Redox Signal 4:749~758
Becker, J. C. / 2007 / Colonic expression of heme oxygenase-1 is associated with a better long-term survival in patients with colorectal cancer / Scand. J. Gastroenterol 42:852~858
Bezerra, D. P. / 2012 / Overview of the therapeutic potential of piplartine(piperlongumine) / Eur. J. Pharm. S 48:453~463
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