Skip to main content

Advertisement

SpringerLink
Log in

Phytocompounds of Onion Target Heat Shock Proteins (HSP70s) to Control Breast Cancer Malignancy

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Globally, breast cancer is one of the leading invasive cancers in women. Moreover, the use of chemotherapeutic drugs for treating cancer produces toxic side effects and has even led to drug resistance. This research paper focuses on targeting three heat shock proteins belonging to 70 kDa subfamily (HSP70s), predominantly, Mortalin, Binding Immunoglobulin Protein (BiP), and Stress Inducible HSP70 (Stress Inducible Heat Shock Protein 70) involved in breast cancer malignancy using different phytocompounds of onion. Phytocompounds of onion (ligands) obtained from different literature sources and the conventional drug, Tamoxifen (standard ligand), used for treating breast cancer are docked against three HSP70s (target proteins) through molecular docking. Molecular docking helps to determine protein–ligand interactions with minimum binding affinity. A comparative analysis revealed that fourteen phytocompounds of onion have lesser binding affinity and formed more stable complexes with the target proteins compared to that of the conventional drug. This evidence can be used and confirmed further through in vitro (cell culture) and in vivo (animal models) studies, and then, these phytocompounds can be modulated efficiently as potential therapeutics for treating breast cancer with less or nearly no side effects.

Graphical Abstract

In Silico work represented here targets three heat shock proteins belonging to 70 kDa subfamily (HSP70s)—Mortalin, Binding Immunoglobulin Protein (BiP), and Stress Inducible HSP70 involved in breast cancer malignancy using different phytocompounds of onion to identify potential phytocompounds that can treat breast cancer with nearly no side effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

Data will be available on request.

Code Availability

Not applicable.

References

  1. Lei, S., Zheng, R., Zhang, S., Wang, S., Chen, R., Sun, K., et al. (2021). Global patterns of breast cancer incidence and mortality: A population-based cancer registry data analysis from 2000 to 2020. Cancer Communications, 41(11), 1183–1194. https://doi.org/10.1002/cac2.12207

    Article  PubMed  PubMed Central  Google Scholar 

  2. Abinaya, M., Priya, S., Karunya, J. R., Ranjani, S., & Hemalatha, S. (2021). Screening the efficacy of compounds from ghee to control cancer: An in silico approach. Biointerface Research in Applied Chemistry., 11(6), 14115–14126. https://doi.org/10.33263/BRIAC116.1411514126

    Article  Google Scholar 

  3. Devlin, E. J., Denson, L. A., & Whitford, H. S. (2017). Cancer treatment side effects: A meta-analysis of the relationship between response expectancies and experience. Journal of Pain and Symptom Management., 54(2), 245-258.E2. https://doi.org/10.1016/j.jpainsymman.2017.03.017

    Article  PubMed  Google Scholar 

  4. Iqbal, J., Abbasi, B., Batool, R., Mahmood, T., Ali, B., Khalil, A., et al. (2018). Potential phytocompounds for developing breast cancer therapeutics: Nature’s healing touch. European Journal of Pharmacology, 827, 125–148. https://doi.org/10.1016/j.ejphar.2018.03.007

    Article  CAS  PubMed  Google Scholar 

  5. Asma, B., & Hemalatha, S. (2022). SARS-CoV-2 Inhibitors from Nigella Sativa. Applied Biochemistry and Biotechnology, 194, 1051–1090. https://doi.org/10.1007/s12010-021-03790-8

    Article  CAS  Google Scholar 

  6. Abraham, J.T., Maharifa, H.N.S., Hemalatha, S. In silico molecular docking approach against enzymes causing Alzheimer’s disease using Borassus flabellifer Linn. Applied Biochemistry and Biotechnology. Published online 2022:1–10. https://doi.org/10.1007/s12010-021-03779-3

  7. Mendie, L. E., & Hemalatha, S. (2022). Molecular docking of phytochemicals targeting GFRs as therapeutic sites for cancer: An in silico study. Applied Biochemistry and Biotechnology., 194(1), 215–231. https://doi.org/10.1007/s12010-021-03791-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dashti, S., Taheri, M., & Ghafouri-Fard, S. (2020). An in-silico method leads to recognition of hub genes and crucial pathways in survival of patients with breast cancer. Science and Reports, 10, 18770. https://doi.org/10.1038/s41598-020-76024-2

    Article  CAS  Google Scholar 

  9. Kabakov, A. E., & Gabai, V. L. (2021). HSP70s in breast cancer: Promoters of tumorigenesis and potential targets/tools for therapy. Cells, 10(12), 3446. https://doi.org/10.3390/cells10123446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang, R., Meng, Z., Wu, X., Zhang, M., Zhang, S., & Jin, T. (2021). Mortalin promotes breast cancer malignancy. Experimental and Molecular Pathology, 118, 104593. https://doi.org/10.1016/j.yexmp.2020.104593

    Article  CAS  PubMed  Google Scholar 

  11. Kulkarni, U., Nayak, V., Prabhu, M. M., & Rao, R. (2020). Tamoxifen-induced vasculitis. Journal of Oncology Pharmacy Practice, 26(3), 735–737. https://doi.org/10.1177/1078155219862342

    Article  PubMed  Google Scholar 

  12. Wang, M., Ma, J., & Zhong, Y. (2021). Ocular toxicity induced by tamoxifen: An overview. Zhonghua Yan Ke Za Zhi, Chinese., 57(3), 232–236. https://doi.org/10.3760/cma.j.cn112142-20200324-00221

    Article  CAS  Google Scholar 

  13. Fung, K., Imeson, J., & Cusano, F. (2018). The clinical significance of QT prolongation associated with tamoxifen: A review of the literature. Journal of Oncology Pharmacy Practice, 24(7), 525–530. https://doi.org/10.1177/1078155217720006

    Article  CAS  PubMed  Google Scholar 

  14. Duman, B., Kuşman, A., Çolak, B., Şenler, F. Ç., & Kumbasar, H. (2020). Tamoxifen-induced acute mania: A case report. Journal of Oncology Pharmacy Practice, 26(8), 2025–2027. https://doi.org/10.1177/1078155220915959

    Article  PubMed  Google Scholar 

  15. Asemani, Y., Zamani, N., Bayat, M., Amirghofran, Z. (2019). Allium vegetables for possible future of cancer treatment. Phytotherapy Research, 33(8). https://doi.org/10.1002/ptr.6490

  16. Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry., 31(2), 455–461. https://doi.org/10.1002/jcc.21334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Osborne, C. (1998). Tamoxifen in the treatment of breast cancer. New England Journal of Medicine, 339(22), 1609–1618. https://doi.org/10.1056/NEJM199811263392207

    Article  CAS  PubMed  Google Scholar 

  18. Lanzotti, V. (2006). The analysis of onion and garlic. Journal of Chromatography A, 1112(1–2), 3–22. https://doi.org/10.1016/j.chroma.2005.12.016

    Article  CAS  PubMed  Google Scholar 

  19. Lanzotti, V., Barile, E., Antignani, V., Bonanomi, G., & Scala, F. (2012). Antifungal saponins from bulbs of garlic, Allium sativum L. var. Voghiera. Phytochemistry, 78, 126–134. https://doi.org/10.1016/j.phytochem.2012.03.009

    Article  CAS  PubMed  Google Scholar 

  20. Fredotović, Ž, Šprung, M., Soldo, B., Ljubenkov, I., Budić-Leto, I., Bilušić, T., et al. (2017). Chemical composition and biological activity of Allium cepa L. and Allium × cornutum (Clementi ex Visiani 1842) methanolic extracts. Molecules., 22(3), 448. https://doi.org/10.3390/molecules22030448

    Article  CAS  PubMed Central  Google Scholar 

  21. Țigu, A. B., Moldovan, C. S., Toma, V. A., Farcaș, A. D., Moț, A. C., Jurj, A., et al. (2021). Phytochemical analysis and in vitro effects of Allium fistulosum L. and Allium sativum L. extracts on human normal and tumor cell lines: A comparative study. Molecules., 26(3), 574. https://doi.org/10.3390/molecules26030574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Fredotović, Ž, Puizina, J., Nazlić, M., Maravić, A., Ljubenkov, I., Soldo, B., et al. (2021). Phytochemical characterization and screening of antioxidant, antimicrobial and antiproliferative properties of Allium × cornutum Clementi and two varieties of Allium cepa L. peel extracts. Plants., 10(5), 832. https://doi.org/10.3390/plants10050832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mullen, W., Edwards, C. A., & Crozier, A. (2006). Absorption, excretion and metabolite profiling of methyl-, glucuronyl-, glucosyl- and sulpho-conjugates of quercetin in human plasma and urine after ingestion of onions. British Journal of Nutrition, 96(1), 107–116. https://doi.org/10.1079/bjn20061809

    Article  CAS  PubMed  Google Scholar 

  24. Wang, T., Zhou, Y., & Cao, G. (2021). Pharmacogenetics of tamoxifen therapy in Asian populations: From genetic polymorphism to clinical outcomes. European Journal of Clinical Pharmacology, 77(8), 1095–1111. https://doi.org/10.1007/s00228-021-03088-y

    Article  CAS  PubMed  Google Scholar 

  25. Wu, Q., Kroon, P. A., Shao, H., Needs, P. W., & Yang, X. (2018). Differential effects of quercetin and two of its derivatives, isorhamnetin and isorhamnetin-3-glucuronide, in inhibiting the proliferation of human breast-cancer MCF-7 cells. Journal of Agriculture and Food Chemistry, 66(27), 7181–7189. https://doi.org/10.1021/acs.jafc.8b02420

    Article  CAS  Google Scholar 

  26. Sharma, K., Mahato, N., Nile, S. H., Lee, E. T., & Lee, Y. (2016). Economical and environmentally-friendly approaches for usage of onion (Allium cepa L.) waste. Food & Function., 7, 3354–3369. https://doi.org/10.1039/c6fo00251j

    Article  CAS  Google Scholar 

  27. Sethi, G., Shanmugam, M. K., Warrier, S., Merarchi, M., Arfuso, F., Kumar, A. P., et al. (2018). Pro-apoptotic and anti-cancer properties of diosgenin: A comprehensive and critical review. Nutrients, 10(5), 645. https://doi.org/10.3390/nu10050645

    Article  CAS  PubMed Central  Google Scholar 

  28. Lee, K. T., Choi, J. H., Kim, D. H., Son, K. H., Kim, W. B., Kwon, S. H., et al. (2001). Constituents and the antitumor principle of Allium victorialis var. platyphyllum. Archives of Pharmacal Research., 24(1), 44–50. https://doi.org/10.1007/BF02976492

    Article  CAS  PubMed  Google Scholar 

  29. Boyle, S. P., Dobson, V. L., Duthie, S. J., Kyle, J. A., & Collins, A. R. (2000). Absorption and DNA protective effects of flavonoid glycosides from an onion meal. European Journal of Nutrition, 39, 213–223. https://doi.org/10.1007/s003940070014

    Article  CAS  PubMed  Google Scholar 

  30. Le Marchand, L. (2002). Cancer preventive effects of flavonoids—A review. Biomedicine & Pharmacotherapy, 56(6), 296–301. https://doi.org/10.1016/S0753-3322(02)00186-5

    Article  Google Scholar 

Download references

Acknowledgements

The authors are very much grateful to the School of Life Sciences, B S Abdur Rahman Crescent Institute of Science and Technology, Chennai, for providing research facilities and also for their constant support and encouragement.

Funding

This project work was sanctioned by the Tamil Nadu State Council for Science and Technology (TNSCST) under the Student Project Scheme (SPS)-Science Stream (2021–2022) Code: MS-017, DOTE Campus, Chennai-600 025, Tamil Nadu, India.

Author information

Authors and Affiliations

  1. School of Life Sciences, B. S. Abdur Rahman Crescent Institute of Science & Technology, Vandalur, Chennai, 600048, India

    Karunya Jenin Ravindranath, Noorul Samsoon Maharifa Haja Mohaideen & Hemalatha Srinivasan

Authors
  1. Karunya Jenin Ravindranath
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Noorul Samsoon Maharifa Haja Mohaideen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hemalatha Srinivasan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Karunya Jenin Ravindranath: Designed art work, performed in silico research, and wrote manuscript. Noorul Samsoon Maharifa Haja Mohaideen: Performed research, analyzed data, designed art work, reviewing and editing. Hemalatha Srinivasan: Conceived, supervision, data curation, validation and project administration.

Corresponding author

Correspondence to Hemalatha Srinivasan.

Ethics declarations

Ethical Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

All authors contributed equally and approved the manuscript for publication.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ravindranath, K.J., Mohaideen, N.S.M.H. & Srinivasan, H. Phytocompounds of Onion Target Heat Shock Proteins (HSP70s) to Control Breast Cancer Malignancy. Appl Biochem Biotechnol 194, 4836–4851 (2022). https://doi.org/10.1007/s12010-022-04016-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-022-04016-1

Keywords

Search

Navigation