Stingless Honeybee’s Rare Sugar and PCSK 9 – LDLR Interaction, A New Hope for Hormone Dependent Breast Cancer Patients – An In-silico Study

Year : 2025 | Volume : 03 | Issue : 01 | Page : 1 6
    By

    Prakash Vaithyanathan,

  1. Science Teacher and Innovator, D3 Drug Tech Lab Private Limited, Majithbstreet, Dharmapuri, Tamil Nadu, India

Abstract

Hypercholesterolemia is a lipid disorder characterized by elevated levels of low-density lipoprotein (LDL), commonly known as “bad” cholesterol. This condition is a significant risk factor in the development and progression of hormone-dependent breast cancer, as well as in the emergence of resistance to hormonal therapy. One of the key regulators of cholesterol metabolism is the proprotein convertase subtilisin/kexin type-9 (PCSK9) protein, which facilitates the degradation of the LDL receptor (LDLR) after binding to it. The reduction of LDL receptors leads to increased circulating LDL cholesterol levels, thereby exacerbating hypercholesterolemia. Recent studies suggest that targeting the PCSK9-LDLR interaction, often referred to as the PCSK9-LDLR axis, may provide a promising strategy for managing hypercholesterolemia while also mitigating the progression of hormone-dependent breast tumors. Small molecule inhibitors that disrupt this interaction have emerged as potential therapeutic agents in both cardiovascular and cancer research. Notably, docking studies have now identified trehalulose, a rare and non-toxic sugar present in the honey produced by stingless honey bees, as a potential candidate for lowering LDL cholesterol levels. By enhancing LDL clearance, trehalulose could offer significant benefits to breast cancer patients globally, presenting a novel and natural approach to cholesterol management and cancer prevention.

Keywords: Hypercholesterolemia, hormone dependent breast cancer, PCSK9, LDLR, stingless honey bee, Trehalulose, bad cholesterol

[This article belongs to International Journal of Cheminformatics ]

How to cite this article:
Prakash Vaithyanathan. Stingless Honeybee’s Rare Sugar and PCSK 9 – LDLR Interaction, A New Hope for Hormone Dependent Breast Cancer Patients – An In-silico Study. International Journal of Cheminformatics. 2025; 03(01):1-6.
How to cite this URL:
Prakash Vaithyanathan. Stingless Honeybee’s Rare Sugar and PCSK 9 – LDLR Interaction, A New Hope for Hormone Dependent Breast Cancer Patients – An In-silico Study. International Journal of Cheminformatics. 2025; 03(01):1-6. Available from: https://journals.stmjournals.com/ijci/article=2025/view=181669


References

  1. Khaldoun S, Wahed A Siddique AB, et al. Pseurotin A as a novel suppressor of hormone dependent breast cancer progression and recurrence by inhibiting PCSK9 secretion and interaction with LDL receptor. Pharmacological Research. 2020; 158:104847.
  2. Siegel RL, Miller KD, Jemal A. Cancer statistics. 2020. CA Cancer J. Clin. 2020; 70: 7–30p.
  3. Lu CW, Lo YH, Chen CH, et al. VLDL and LDL, but not HDL, promote breast cancer cell proliferation, metastasis and angiogenesis. Cancer Lett. 2017, 388, 130–8p.
  4. Guan X, Liu Z, Zhao Z, et al. Emerging roles of low-density lipoprotein in the development and treatment of breast cancer. Lipids Health Dis. 2019; 18: 1-9p.
  5. White CP. On the occurrence of crystals in tumours. J. Pathol. Bacteriol. 1909. 13 (1), 3–10.
  6. Kuzu O, Noory MA, Robertson GP. The role of cholesterol in cancer. Cancer Res. 2016, 76, 2063–2070p.
  7. Mcdonnell DP, Park S, Goulet MT, et al. Obesity, cholesterol metabolism, and breast cancer pathogenesis. Cancer Res. 2014; 74: 4976–82p.
  8. Huang JF, Li, Lian JH, et al. Tumor-induced hyperlipidemia contributes to tumor growth. Cell Rep. 2016, 15, 336–48p.
  9. Gabitova L, Gorin A, Astsaturov I. Molecular pathways: Sterols and receptor signaling in cancer. Clin. Cancer Res. 2014; 19(23): 6344–50p.
  10. Fletcher MT, Hungerford NL, Webber D, et al. Stingless bee honey, a novel source of trehalulose: a biologically active disaccharide with health benefits. Sci Rep. 2020; 10: 1-8p.
  11. https://pubchem.ncbi.nlm.nih.gov/compound/162104
  12. https://www.rcsb.org/structure/3gcw
  13. McNutt MC, Kwon HJ, Chen CY et al. Antagonism of Secreted PCSK9 Increases Low Density Lipoprotein Receptor Expression in HepG2 Cells. J. Biol. Chem. 2009; 284 (16): 10561 – 10570.
  14. Hajar R. PCSK9 Inhibitors: A Short History and a New Era of Lipid-lowering Therapy. Heart Views. 2019; 20(2):74-75p.
  15. Agnello F, Mauro MS, Rochira C, et al. PCSK9 inhibitors: current status and emerging frontiers in lipid control. Expert Review of Cardiovascular Therapy. 2024; 22(1-3): 41-58p.
  16. Mercep I, Strikic D. Hrabac P, et al. PCSK9 inhibition: from effectiveness to cost-effectiveness. Frontiers in Cardiovascular Medicine, 2024; 1-9p.
  17. Safarova M, Bimal T, Soffer DE, et al. Advances in targeting LDL cholesterol: PCSK9 inhibitors and beyond. American Journal of Preventive Cardiology. 2024; 19:1-11.
Regular Issue Subscription Original Research
Volume 03
Issue 01
Received 01/11/2024
Accepted 08/11/2024
Published 16/04/2025
Publication Time 166 Days
470

Login


My IP

PlumX Metrics