Synergic effects of artemisinin and resveratrol in cancer cells
The aim of this study was to investigate whether resveratrol (Res) combined with artemisinin (ART) possess synergistic effect on different cancer cells.
Materials and methods
The viability of HepG2 and HeLa cells treated with ART and Res was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Combination index (CI) analysis and isobologram were used to assess the synergistic effect of ART and Res in different ratios. Wound-healing assay was used to investigate the migration rate. AO staining and fluorescent microscopy measurements were performed to detect the cell apoptosis. Reactive oxygen species (ROS) was measured with 2′7′-dichlorofluorescein diacetate (DCFH-DA).
MTT assay indicated that ART and Res inhibited the growth of HeLa and HepG2 cells in a dose-dependent manner. The combination of ART and Res exhibited the strongest anticancer effect at the ratio of 1:2 (ART to Res). The combination of the two drugs also markedly reduced the ability of cell migration. Apoptosis analysis showed that combination of ART and Res significantly increased the apoptosis and necrosis rather than use singly. Additionally, ROS levels were elevated by combining ART with Res.
Taken together, the present study suggested that ART and Res possessed the synergistic anti-tumor effect. ART in combination with Res could be an effective therapeutic strategy for cancer.
KeywordsArtemisinin Resveratrol Synergistic effect Migration Apoptosis Reactive oxygen species
- Khan MA, Chen HC, Wan XX, Tania, M, Xu AH, Chen FZ, Zhang DZ (2013) Regulatory effects of resveratrol on antioxidant enzymes: A mechanism of growth inhibition and apoptosis induction in cancer cells. Mol Cells, 1–7Google Scholar
- Liu P, Liang H, Xia Q, Li P, Kong H, Lei P, Tu Z et al (2013) Resveratrol induces apoptosis of pancreatic cancers cells by inhibiting miR-21 regulation of BCL-2 expression. Clin Transl Oncol pp 1–6Google Scholar
- Notas G, Nifli AP, Kampa M, Vercauteren J, Kouroumalis E, Castanas E (2006) Resveratrol exerts its antiproliferative effect on HepG2 hepatocellular carcinoma cells, by inducing cell cycle arrest, and NOS activation. Biochimica et Biophysica Acta (BBA)-General Subjects 1760(11):1657–1666Google Scholar
- Tan WF, Shen F, Luo XJ, Su CQ et al (2011) Artemisinin inhibits in vitro and in vivo invasion and metastasis of human hepatocellular carcinoma cells. Phytomedicine 18(2):158–162Google Scholar
- Tin AS, Sundar SN, Tran KQ, Park AH, Poindexter KM, Firestone GL (2012) Antiproliferative effects of artemisinin on human breast cancer cells requires the downregulated expression of the E2F1 transcription factor and loss of E2F1-target cell cycle genes. Anticancer Drugs 23(4):370–379PubMedCrossRefGoogle Scholar
- Willoughby JA, Sundar SN, Cheung M, Tin AS, Modiano J, Firestone GL (2009) Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression. J Biol Chem 284(4):2203–2213PubMedCentralPubMedCrossRefGoogle Scholar
- World Health Organization (2006) Guidelines for the treatment of malaria. World Health OrganizationGoogle Scholar
- Xu H, He Y, Yang X, Liang L, Zhan Z, Ye Y, Sun L et al (2007) Anti-malarial agent artesunate inhibits TNF-α-induced production of proinflammatory cytokines via inhibition of NF-κB and PI3 kinase/Akt signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes. Rheumatology 46(6):920–926PubMedCrossRefGoogle Scholar
- Zhu HL, Huang X (2011) Resveratrol and its analogues: promising antitumor agents. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents) 11(5):479–490Google Scholar