Molecular Simulations Identify Target Receptor Kinases Bound by Astaxanthin to Induce Breast Cancer Cell Apoptosis

Mossa Gardaneh (1), Zahra Nayeri (2), Parvin Akbari (3), Mahsa Gardaneh (4), Hasan Tahermansouri (5)
(1) ,
(2) Department of Stem Cells and Regenerative Medicine, Division of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Iran, Islamic Republic of,
(3) , Iran, Islamic Republic of,
(4) , Canada,
(5) , Iran, Islamic Republic of

Abstract

Background: We investigated molecular mechanisms behind astaxanthinmediated induction of apoptosis in breast cancer cell lines toward combination therapy against cancer drug resistance.


Methods: Breast cancer cell lines were treated with serial concentrations of astaxanthin to determine its IC50. We used drug-design software to predict interactions between astaxanthin and receptor tyrosine kinases or other key gene products involved in intracellular signaling pathways. Changes in gene expression were examined using RT-PCR. The effect of astaxanthin-nanocarbons combinations on cancer cells was also evaluated.


Results: Astaxanthin induced cell death in all three breast cancer cell lines was examined so that its IC50 in two HER2-amplifying lines SKBR3 and BT-474 stood, respectively, at 36 and 37 ?M; however, this figure for MCF-7 was significantly lowered to 23 ?M (P<0.05). Astaxanthin-treated SKBR3 cells showed apoptotic death upon co-staining. Our in silico examinations showed that some growth-promoting molecules are strongly bound by astaxanthin via their specific amino acid residues with their binding energy standing below -6 KCa/Mol. Next, astaxanthin was combined with either graphene oxide or carboxylated multi-walled carbon nanotube, with the latter affecting SKBR cell survival more extensively than the former (P<0.05). Finally, astaxanthin coinduced tumor suppressors p53 and PTEN but downregulated the expression of growth-inducing genes in treated cells.


Conclusion: These findings indicate astaxanthin carries' multitarget antitumorigenic capacities and introduce the compound as a suitable candidate for combination therapy regimens against cancer growth and drug resistance. Development of animal models to elucidate interactions between the compound and tumor microenvironment could be a major step forward towards the inclusion of astaxanthin in cancer therapy trials.

Full text article

Generated from XML file

Authors

Mossa Gardaneh
mossabenis65@gmail.com (Primary Contact)
Zahra Nayeri
Parvin Akbari
Mahsa Gardaneh
Hasan Tahermansouri
1.
Gardaneh M, Nayeri Z, Akbari P, Gardaneh M, Tahermansouri H. Molecular Simulations Identify Target Receptor Kinases Bound by Astaxanthin to Induce Breast Cancer Cell Apoptosis. Arch Breast Cancer [Internet]. 2020 May 31 [cited 2024 May 28];:72-8. Available from: https://www.archbreastcancer.com/index.php/abc/article/view/298

Article Details