title: Plumbagin reduces chronic lymphocytic leukemia cell survival by downregulation of Bcl-2 but upregulation of the Bax protein level.
abstract: Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis rates. The aberration of apoptosis-related genes in CLL cells results in defective apoptosis of CLL cells in response to traditional therapeutic medicine. Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a natural compound from Plumbago zeylinica, has been shown to exhibit pro-apoptotic activities in tumor cells. In the present study, we report that plumbagin effectively inhibited CLL cell viability with a lower dose compared to fludarabine, and inhibited cell proliferation in a dose-dependent manner. In addition, plumbagin promoted accumulation of MEC-1 cells in the S phase, and blocked cell cycle transition of HG3 cells from G0/G1 to S phase. Molecularly, plumbagin markedly induced CLL cell apoptosis through reduction of Bcl-2, but through an increase in the Bax protein level. These results suggest that plumbagin may be considered as a potential anticancer agent for CLL therapy.
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Fu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Xuanxuan
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Zengtian
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Mingshan
authors.initials: M
authors.lastname: Niu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sang
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology*; D009285:Naphthoquinones / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C000595707:BCL2 protein, human; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C014758:plumbagin