Platycodin D induces apoptosis in MCF-7 human breast cancer cells.
Platycodin D (PD), a major constituent isolated from the root of Platycodon grandiflorum, has been suggested to possess anticancer activities, as indicated by its capabilities to induce mitotic arrest and apoptosis in several cancer cells. However, little is known of the underlying action mechanism. This study is the first to investigate the anticancer effect of PD in the human breast cancer cell, MCF-7. Our data showed that PD exhibited marked cell growth inhibition by inducing apoptosis. This induction was associated with activation of caspase-8 and -9 activities and poly(ADP-ribose) polymerase. PD triggered the mitochondrial apoptotic pathway, as indicated by up-regulation of levels of cellular Bax and down-regulation of levels of Bcl-2 and caspase-9 activation. We found that PD induced proteolytic activation of Bid, a member of the proapoptotic Bcl-2 family, implicating PD-induced apoptosis as possibly being functionally linked to a death receptor-mediated pathway. The PD treatment also was accompanied by an increase in cellular generation of reactive oxygen species, indicating that PD-induced apoptosis is likely to be mediated through mitochondrial dysfunction. In addition, we revealed that the mitogen-activated protein kinases, including extracellular signal-regulated kinase 1/2, c-Jun NH(2)-terminal kinase 1/2, and p38, which play important roles in apoptosis, were activated by treatment with PD. These results provide a basic mechanism for the anticancer properties of PD and suggest that PD is a promising candidate for chemotherapy and chemoprevention of breast cancer.
Yu
Ji Sun
JS
College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
Kim
An Keun
AK
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D031238:Platycodon / Q000737:chemistry*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D053218:Receptors, Death Domain; D012503:Saponins; D014315:Triterpenes; D011064:Poly Adenosine Diphosphate Ribose; C108953:platycodin D; D011065:Poly(ADP-ribose) Polymerases; D020928:Mitogen-Activated Protein Kinases; D053181:Caspase 8; D053453:Caspase 9