Effect of artesunate on inhibiting proliferation and inducing apoptosis of SP2/0 myeloma cells through affecting NFkappaB p65.
The initial treatment of multiple myeloma (MM) experienced a paradigm shift, in the past decade, with the introduction of novel agents such as thalidomide, lenalidomide and bortezomib, leading to improved outcomes. High dose therapy and autologous stem cell transplantation remain an important therapeutic option for patients with MM eligible for the procedure. However, most of these treatment regimens are too expensive for Chinese patients. Therefore, we investigated the effects of artesunate, which is commonly used in the treatment of severe malaria, on inhibition of proliferation and induction of apoptosis of a mouse myeloma cell line SP2/0. The growth inhibition of SP2/0 cell proliferation induced by artesunate (ART) treatment was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and the rate of apoptosis and cell cycle changes induced by ART were analyzed by flow cytometry. ART-induced morphology changes of apoptosis in SP2/0 cells, as observed by light and transmission electron microscopy. Additionally, DNA laddering, which is a hallmark of apoptosis, was observed by agarose gel electrophoresis of DNA harvested from SP2/0 cells treated with ART. The levels of nuclear factor kappa B p65 (NFkappaB p65) protein in nucleus and the inhibitor of NFkappaB (IkappaBalpha) in the cytoplasm were measured by western blot analysis and ELISA to evaluate NFkappaB p65 transcription activity indirectly. The results show that artesunate inhibited the proliferation and induced apoptosis of SP2/0 cells in a dose- and time-dependent manner. Artesunate also increased the proportion of SP2/0 cells in G0/G1 phase, while decreased the proportion of cells in G2/M or S phase. Additionally, artesunate treatment decreased the level of NFkappaB p65 protein in the nucleus, while increased the level of IkappaBalpha protein in the cytoplasm. The present result is the first report to show that artesunate may be useful in the treatment of MM.
Li
Shihui
S
Department of Hematology, The Second Hospital of Hebei Medical University, 215, Heping Xi Road, 050000, Shijiazhuang City, People's Republic of China.
Xue
Fang
F
Department of Hematology, The Second Hospital of Hebei Medical University, 215, Heping Xi Road, 050000, Shijiazhuang City, People's Republic of China.
Cheng
Zhiyong
Z
Department of Hematology, The Second Hospital of Hebei Medical University, 215, Heping Xi Road, 050000, Shijiazhuang City, People's Republic of China.
Yang
Xiaoyang
X
Department of Hematology, Affiliated Haikou Hospital, Xiangya School of Medicine, Central South University, Haikou Municipal Hospital, 570208, Haikou, People's Republic of China.
Wang
Suyun
S
Department of Hematology, The Second Hospital of Hebei Medical University, 215, Heping Xi Road, 050000, Shijiazhuang City, People's Republic of China.
Geng
Fengyong
F
Department of General Surgery, Aviation Central Hospital, No. 3, Anwai Bei Yuan, ChaoYang District, 100012, Peking City, People's Republic of China.
Pan
Ling
L
Department of Hematology, The Second Hospital of Hebei Medical University, 215, Heping Xi Road, 050000, Shijiazhuang City, People's Republic of China. lingpan20002000@yahoo.com.cn.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D009368:Neoplasm Transplantation; D011506:Proteins / Q000378:metabolism; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D037621:Artemisinins; D000077332:Artesunate; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D051996:Transcription Factor RelA; C454819:Nfkbid protein, mouse; C498144:Rela protein, mouse