This is an unedited manuscript accepted for publication and provided as an Article in Press for early access at the author’s request. The article will undergo copyediting, typesetting, and galley proof review before final publication. Please be aware that errors may be identified during production that could affect the content. All legal disclaimers of the journal apply.
Prakash Vaithyanathan,
- Science Teacher and Innovator, 50 L.B. Road, Adyar, Chennai, Tamil Nadu, India
Abstract document.addEventListener(‘DOMContentLoaded’,function(){frmFrontForm.scrollToID(‘frm_container_abs_111646’);});Edit Abstract & Keyword
Hypercholesterolemia, a lipid disorder responsible for high levels of low-density lipoprotein (LDL) or ‘bad’ cholesterol, is a factor contributing to the progression of hormone-dependent breast cancer and the development of resistance to hormonal therapy. Proprotein convertase subtilisin/kexin type-9 (PCSK9) protein regulates cholesterol metabolism by promoting the degradation of the LDL receptor (LDLR) after binding to it. Preliminary research has shown that inhibiting the PCSK9-LDLR interaction, known as the PCSK9-LDLR axis, with small molecules may help manage hypercholesterolemia and suppress the growth and recurrence of hormone-dependent breast tumors. For the first time, docking studies have shown that a rare and non-toxic sugar, trehalulose, found in the honey produced by stingless honey bees, can aid in clearing LDL cholesterol, potentially benefiting breast cancer patients worldwide.
Keywords: Bad cholesterol, hormone-dependent breast cancer, hypercholesterolemia, LDLR, PCSK9, stingless honey bee, trehalulose.
Prakash Vaithyanathan. Stingless Honey Bee’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. 2024; ():-.
Prakash Vaithyanathan. Stingless Honey Bee’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. 2024; ():-. Available from: https://journals.stmjournals.com/ijci/article=2024/view=0
References
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- 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.
- Siegel RL, Miller KD, Jemal A. Cancer statistics. 2020. CA Cancer J. Clin. 2020; 70: 7–30p.
- 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.
- 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.
- White CP. On the occurrence of crystals in tumours. J. Pathol. Bacteriol. 1909. 13 (1), 3–10.
- Kuzu O, Noory MA, Robertson GP. The role of cholesterol in cancer. Cancer Res. 2016, 76, 2063–2070p.
- Mcdonnell DP, Park S, Goulet MT, et al. Obesity, cholesterol metabolism, and breast cancer pathogenesis. Cancer Res. 2014; 74: 4976–82p.
- Huang JF, Li, Lian JH, et al. Tumor-induced hyperlipidemia contributes to tumor growth. Cell Rep. 2016, 15, 336–48p.
- Gabitova L, Gorin A, Astsaturov I. Molecular pathways: Sterols and receptor signaling in cancer. Clin. Cancer Res. 2014; 19(23): 6344–50p.
- 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.
- https://pubchem.ncbi.nlm.nih.gov/compound/162104
- https://www.rcsb.org/structure/3gcw
- 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.
- Hajar R. PCSK9 Inhibitors: A Short History and a New Era of Lipid-lowering Therapy. Heart Views. 2019; 20(2):74-75p.
- 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.
- Mercep I, Strikic D. Hrabac P, et al. PCSK9 inhibition: from effectiveness to cost-effectiveness. Frontiers in Cardiovascular Medicine, 2024; 1-9p.
- 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.
| Volume | |
| Received | 01/11/2024 |
| Accepted | 08/11/2024 |
| Published | 08/11/2024 |
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