Plumbagin induces ROS-mediated apoptosis in human promyelocytic leukemia cells in vivo.
Plumbagin, a naphtoquinone from the roots of Plumbago zeylanica is known to possess anticancer and anti-bacterial activity. Based on the former finding of our group in vitro demonstrating its effectiveness in human promyelocytic leukemia cells, NB4, in this study we further revealed the mitochondrial pathway involved in plumbagin-induced apoptosis. We also found that the generation of ROS was a critical mediator in plumbagin-induced apoptosis, which would be abrogated completely by antioxidant, NAC. The anticancer effect of plumbagin was investigated in vivo using NB4 tumor xenograft in NOD/SCID mice. The incidence of formation, growth characteristics, body weight and volume of tumors were observed. The histopathologic examination of tumors and organs were made. The results showed that intraperitoneal injection of plumbagin (2mg/kg body weight) daily for 3 weeks resulted to a 64.49% reduction of tumor volume compared with the control. Furthermore, there was no overt manifestation of toxicity such as weight loss, tissue damage and behavior change which appeared in Doxorubicin-treated mice (1mg/kg thrice a week). These results indicate that plumbagin has potential as a novel therapeutic agent for myeloid leukemia.
Xu
Kai-Hong
KH
Peking University People's Hospital, Institute of Hematology, Beijing, China.
Lu
Dao-Pei
DP
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009285:Naphthoquinones / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects; D017382:Reactive Oxygen Species; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D020169:Caspases; C014758:plumbagin