Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Indole-3-acetate induces apoptosis and stimulates phosphorylation of p65NF-KB in 143B and HOS osteosarcoma cells

Yanhui Zhang¹, Yang Li¹, Chao Wang¹, Kewen Zheng², Chen Feng², Wenbo Wang¹

¹Department of Orthopaedic Surgery, First Affiliated Hospital of Harbin Medical University, Harbin 150010; ²Department of Orthopaedic Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang 157011, China.

For correspondence:- Wenbo Wang Email: WadsworthCbeish@yahoo.com

Accepted: 17 June 2018 Published: 28 July 2018

Citation: Zhang Y, Li Y, Wang C, Zheng K, Feng C, Wang W. Indole-3-acetate induces apoptosis and stimulates phosphorylation of p65NF-KB in 143B and HOS osteosarcoma cells. Trop J Pharm Res 2018; 17(7):1279-1285 doi: 10.4314/tjpr.v17i7.8

© 2018 The authors.
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Abstract

Purpose: To investigate the effect of indole-3-acetate (IAA) on the proliferation of 143B and HOS osteosarcoma cells, and its mechanism of action.

Methods: Indole-3-acetate (IAA)-induced changes in cell proliferation and apoptosis were investigated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. The effects of IAA on expressions of mRNAs for phosphatase and tensin homolog (PTEN), fas ligand (FasL), and fas receptor (FasR) were evaluated using western blot assay.

Results: Early apoptosis in 143B cell cultures due to addition of IAA (5 µM) was 34.67 %, relative to 2.82 % in untreated cultures. In HOS cells, IAA caused 39.21 % apoptosis, relative to 3.53 % apoptosis in control. The addition of IAA to the cell cultures significantly enhanced the expressions of mRNAs for PTEN, FasL and FasR, compared to untreated cells (p < 0.05). Western blot analysis showed that IAA caused a significant decrease in the level of IκBα expression in both cell lines (p < 0.05). In 143B and HOS cells, treatment with IAA led to accumulation of higher levels of NF-κB in the nucleus than in the cytosol. The levels of cytosolic NF-κB, and nuclear lamin B1 in IAA-treated cells were lower than the corresponding levels in untreated cells.

Conclusion: These results indicate that IAA inhibits proliferation, and induces apoptosis in 143B and HOS cells via activation of NF-κB, and its translocation to the nucleus. Therefore, IAA may be a useful drug target in the treatment of osteosarcoma.

Keywords: Indole-3-acetate, Phosphatase, Fas receptor, Translocation, Proliferation, Tumoricidal activity