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Open Access Highly Accessed Research article

Involvement of Seladin-1 in goniothalamin-induced apoptosis in urinary bladder cancer cells

Heng Kai Yen15, Afifah-Radiah Fauzi1, Laily Bin Din2, Valerie J McKelvey-Martin3, Chan Kok Meng45, Salmaan Hussain Inayat-Hussain45 and Nor Fadilah Rajab15*

Author Affiliations

1 Biomedical Science Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

2 Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600 Selangor, Malaysia

3 School of Pharmacy and Pharmaceutical Sciences, University of Ulster, Coleraine BT52 1SA, United Kingdom

4 Environmental Health and Industrial Safety Science Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

5 Toxicology Laboratory, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

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BMC Complementary and Alternative Medicine 2014, 14:295  doi:10.1186/1472-6882-14-295

Published: 9 August 2014

Abstract

Background

Selective Alzheimer Disease Indicator-1 (or Seladin-1) is a multifunctional protein first discovered by downregulation of its expression in Alzheimer’s disease. Interestingly, the expression of this protein is upregulated in several cancers, including primary bladder cancer. However, its role in cancer formation has yet to be discovered. Goniothalamin is a natural product that has been demonstrated to induce apoptosis in various cancer cell lines. In this study, we have elucidated the role of Seladin-1 in goniothalamin-induced cytotoxicity towards human urinary bladder cancer cell line RT4.

Methods

The cytotoxicity of goniothalamin in human urinary bladder cancer cell line RT4 was assessed using MTT assay and the mode of cell death was determined by Annexin V-FITC/PI labeling assay. Finally, the expression of Seladin-1 protein in goniothalamin-treated RT4 cells was determined by Western blot.

Results

MTT assay showed that the cytotoxicity of goniothalamin on RT4 cells was concentration and time dependent with IC50 values of 61 μM (24 hr), 38 μM (48 hr) and 31 μM for 72 hr, respectively. Cell death induced was confirmed through apoptosis; as assessed using the Annexin V-FITC/PI labeling assay. Furthermore, the involvement of Seladin-1 in goniothalamin-induced apoptosis was evidenced through the cleavage of 60 kDa protein to 40 kDa and 20 kDa. This was followed by a gradual increase of 20 kDa fragment suggesting the involvement of Seladin-1 in goniothalamin-induced apoptosis on RT4 cells.

Conclusion

This study demonstrates that goniothalamin induce cytotoxicity and apoptosis on RT4 cells. The involvement of Seladin-1 in goniothalamin-induced apoptosis further suggested that Seladin-1 may play a role in the formation of primary bladder cancer.

Keywords:
Seladin-1; Bladder cancer; Goniothalamin; Apoptosis