, Volume 20, Issue 8, pp 1122–1133 | Cite as

Alantolactone induces G1 phase arrest and apoptosis of multiple myeloma cells and overcomes bortezomib resistance

  • Yao Yao
  • Dandan Xia
  • Yueping Bian
  • Yueyue Sun
  • Feng Zhu
  • Bin Pan
  • Mingshan Niu
  • Kai Zhao
  • Qingyun Wu
  • Jianlin Qiao
  • Chunling Fu
  • Zhenyu LiEmail author
  • Kailin XuEmail author
Original Paper


Several sesquiterpene lactones have been extracted and demonstrated to exert various pharmacological functions in a variety of cancers. Here, we investigated anti-tumor effect of alantolactone, an allergenic sesquiterpene lactone, on human multiple myeloma (MM) and showed alantolactone inhibited growth of MM cells, both in the presence or absence of bone marrow (BM)-derived stromal cells (HS-5), and subsequent G1 phase arrest, and apoptosis as demonstrated by increased Annexin-V/7-AAD binding, caspase-3 or caspase-9 activation and down-modulation of activation of extracellular signal-regulated kinases 1/2. In addition, alantolactone reduced the secretion of MM survival and growth-related cytokines, vascular endothelial growth factor, from MM cells or HS-5 cells, and inhibited cytokine-induced osteoclastogenesis. Notably, alantolactone also inhibited cell proliferation in bortezomib-resistant MM cells. Taken together, alantolactone exerted anti-tumor effect on MM by suppressing cell proliferation, triggering apoptosis, partly damaging the BM microenvironment and overcoming proteasome inhibitor resistance, suggesting alantolactone may be a novel therapeutic approach for the treatment of human MM.


Alantolactone Multiple myeloma Cytotoxicity Bortezomib resistance ERK1/2 



Multiple myeloma


Extracellular signal-regulated kinases1/2


Vascular endothelial growth factor


Bone marrow




b-Fibroblast growth factor


Hepatocyte growth factor


Insulin-like growth factor-1


Mitogen-activated protein kinases


Chronic myelogenous leukemia


Testes-specific protease 50


Dimethyl sulfoxide


Propidium iodide

RNase A

Ribonuelease A


Macrophage colony-stimulating factor


Soluble receptor activator of NFκB


Enzyme-linked immunosorbent assay


Cyclin-dependent kinase


Osteoclast cell



This work was supported by the National Natural Science Foundation of China (81302034, 81272622).

Conflict of interest

The authors have no conflict of interest to declare.

Supplementary material

10495_2015_1140_MOESM1_ESM.docx (4.3 mb)
Supplementary material 1 (DOCX 4374 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of HematologyThe Affiliated Hospital of Xuzhou Medical CollegeXuzhouChina
  2. 2.Blood Diseases InstituteXuzhou Medical CollegeXuzhouChina
  3. 3.Key Laboratory of Bone Marrow Stem Cell, Jiangsu ProvinceXuzhou Medical CollegeXuzhouChina

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