Natural bioactive 4-Hydroxyisophthalic acid (4-HIPA) exhibited antiproliferative potential by upregulating apoptotic markers in in vitro and in vivo cancer models

Abstract

There is tremendous scope for identifying novel anti-cancer molecules from the unexplored reserves of plant kingdom. The application of dietary supplementation or medicine derived from such sources is a promising approach towards treatment of cancer. In the present study we have evaluated the antiproliferative potential of 4-hydroxyisophthalic acid (4-HIPA), which is a novel antioxidant compound isolated from the roots of the aqueous extract of Decalepis hamiltonii. 4-HIPA was screened in vitro against human breast cancer cell lines MCF-7, MDA-MB-468 and normal human breast epithelial cell MCF-10, and demonstrated that human breast cancer cell lines, in contrast to MCF-10, are sensitive to 4-HIPA .4-HIPA showed marked reduction in cell viability and short-term proliferation assays in these cells. Results of the long-term colony formation and scratch assay further reaffirmed that 4-HIPA inhibited the growth and proliferation in breast cancer cells. We further conducted in vivo studies using murine Ehrlich Ascites Tumor (EAT) cell model. Our in vivo results established that treatment with 4-HIPA reduced the tumorigenesis by promoting apoptosis in EAT-bearing mice. The results of our molecular docking predictions further warranted our claim. This study is valuable as 4-HIPA exhibits antiproliferative potential that can be exploited in the development of anticancer drugs.

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Abbreviations

4-HIPA:

4-Hydroxyisophthalic acid

CP:

Cyclophosphamide

EAT:

Ehrlich ascites tumor cells

LDH:

Lactate dehydrogenase

ALT:

Alanine transaminases

AST:

Aspartate transaminases

ALP:

Alkaline phosphatase

MST:

Mean survival time

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Acknowledgements

The correspondent author wishes to thank Prof. Cletus D'Souza, the Head of the Department of Biochemistry, University of Mysore, for his support and guidance at the time of this study.

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Correspondence to T. Shivanandappa or Mahsa Zarei.

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Zarei, M., Shivanandappa, T. & Zarei, M. Natural bioactive 4-Hydroxyisophthalic acid (4-HIPA) exhibited antiproliferative potential by upregulating apoptotic markers in in vitro and in vivo cancer models. Mol Biol Rep (2020). https://doi.org/10.1007/s11033-020-05617-x

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Keywords

  • Bioactive compound
  • 4-hydroxyisophthalic acid
  • Anti-tumor
  • pro-apoptosis
  • EAT model
  • Molecular docking