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Anti-tumor effects of dihydroartemisinin on human osteosarcoma

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Abstract

Dihydroartemisinin (DHA) exhibits antitumor activity against a wide spectrum of cancer cells. However, whether DHA has anti-tumor effect on human osteosarcoma cells remains unknown. This study aims to investigate the anti-tumor activity of DHA and the underlying mechanisms in human osteosarcoma cell lines with different p53 mutation statuses. Four human osteosarcoma cell lines were treated with different concentrations of DHA. Then, cell proliferation was determined by the CCK-8 viability assay; apoptosis and cell cycle progression were evaluated by flow cytometry; protein expression was analyzed by western blot assay; and NF-kB activity was examined by luciferase assay. The results demonstrated that DHA treatment could inhibit the proliferation of four osteosarcoma cell lines in a dose-dependent manner. P53 wild-type osteosarcoma cells were more sensitive to DHA. Moreover, the percentage of apoptotic cell and cell arrest in G2/M phase was increased upon DHA treatment in a dose-dependent manner. Mechanistically, DHA activated caspase-3, caspase-8, and caspase-9; upregulated the expression of Bax, FAS, and cyclin D1; downregulated the expression of Bcl-2, Cdc25B, and cyclin B1; and inhibited the activity of NF-кB. In conclusion, DHA has significant anticancer effects against human osteosarcoma cells, which include induction of apoptosis and cell cycle arrest. The p53 gene may play a certain role in the DHA-induced human osteosarcoma apoptosis and cell cycle arrest. DHA is a novel anti-osteosarcoma drug candidate that merits further study.

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Abbreviations

DHA:

Dihydroartemisinin

DMSO:

Dimethyl sulfoxide

MEM:

Modified eagle medium

FBS:

Fetal bovine serum

BCA:

Bicinchoninic acid

CCK-8:

Cell counting kit-8

ATCC:

American type culture collection

PS:

Phosphatidylserine

TNF:

Tumor necrosis factor

FASL:

Fas ligand

FADD:

Fas-associated protein with death domain

NF-кB:

Nuclear factor-kappa b

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Acknowledgments

The authors appreciate the suggestions of Dr. Hua Chen, the First Affiliated Hospital of Harbin Medical University. The authors also thank the anonymous reviewers for their insightful comments.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng St., Nangang District, Harbin, Heilongjiang, 150001, China

    Ye Ji, Yi-Cai Zhang, Liu-Bao Pei & Jing-Long Yan

  2. Department of Cadres Ward, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China

    Li-Li Shi

  3. Department of Laboratory Diagnostics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China

    Xue-Hua Ma

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  1. Ye Ji
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Correspondence to Jing-Long Yan.

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Ye Ji and Yi-Cai Zhang contributed equally.

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Ji, Y., Zhang, YC., Pei, LB. et al. Anti-tumor effects of dihydroartemisinin on human osteosarcoma. Mol Cell Biochem 351, 99–108 (2011). https://doi.org/10.1007/s11010-011-0716-6

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