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Molecular and Cellular Biochemistry

, Volume 451, Issue 1–2, pp 79–90 | Cite as

(I-3,II-3)-Biacacetin-mediated cell death involves mitochondria

  • Jyotsna Nambiar
  • Gayathri Vijayakumar
  • G. Drishya
  • Sanu K. Shaji
  • Nanjan Pandurangan
  • Geetha B. Kumar
  • Bipin G. NairEmail author
Article

Abstract

Dysregulation of the dynamic balance between cell proliferation and cell death leads to several malignancies including cancer. Biflavones are known to possess anti-proliferative activity against numerous cancer cell lines. The current study was undertaken to understand the mechanism of action of the biflavonoid (I-3,II-3)-biacacetin on MDA-MB-231. Biacacetin induces dose-dependent cell death in MDA-MB-231 cells from concentrations as low as 0.5 μM, which was further confirmed by an increase in sub-G1 cells. Furthermore, the cell death induced by biacacetin was found to be mitochondria-dependent, since cells devoid of mitochondria were viable in the presence of biacacetin even at the highest concentration tested (25 μM). Fluorescence studies clearly indicated nuclear changes and apoptotic body formation that are characteristic of apoptosis. These results were further corroborated by studies that demonstrate biacacetin to regulate several key markers of apoptosis like Caspase 3, p53, Bax, and poly-ADP-ribose polymerase-1. Furthermore, biacacetin did not induce cell death in normal macrophage cell line, RAW at concentrations up to 15 μM. In addition to MDA-MB-231 cells, biacacetin also induces apoptotic cell death in the highly chemo-resistant cell line, OVISE, where the cells stained positive for annexin. Biacacetin also induces cell death in the highly malignant fibrosarcoma cell line HT1080. Furthermore, biacacetin also induces significant cell death (50%) in 3D tumor spheroids, at a concentration of 25 μM. Taken together, these results provide an understanding of biacacetin-mediated cell death and thereby provides a strong basis for the use of such compounds as novel templates for anti-cancer therapeutics.

Keywords

Biacacetin Cell death Mitochondria Apoptosis 

Notes

Acknowledgements

We acknowledge Mata Amritanandamayi Devi, Chancellor, Amrita Vishwa Vidyapeetham (Amrita University) for being the inspiration behind this study. We would like to acknowledge Dr. Vinay Tergaonkar and Dr. Manikandan Lakshmanan, Institute of Molecular and Cell Biology, A*STAR, Singapore for all the studies with OVISE cells. This work was supported by Institutional funding (Amrita University Research) grant (BGN).

Author contributions

Participated in research design: Nair, Kumar, and Nambiar. Conducted experiments: Nambiar, Drishya, Vijayakumar, and Shaji. Contributed new reagents or analytic tools: Pandurangan. Performed data analysis: Nambiar, Drishya, Vijayakumar, and Shaji. Wrote or contributed to the writing of the manuscript: Nambiar, Kumar, and Nair.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

Supplementary material

11010_2018_3395_MOESM1_ESM.docx (1018 kb)
Supplementary material 1 (DOCX 1018 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jyotsna Nambiar
    • 1
  • Gayathri Vijayakumar
    • 1
  • G. Drishya
    • 1
  • Sanu K. Shaji
    • 1
  • Nanjan Pandurangan
    • 1
  • Geetha B. Kumar
    • 1
  • Bipin G. Nair
    • 1
    Email author
  1. 1.Amrita School of Biotechnology, Amrita Vishwa VidyapeethamAmrita UniversityKollamIndia

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