Asarone Possesses Antiproliferative Potential in Breast Cancer Cell Line (MCF-7) Through Via Apoptosis and Inflammatory-Mediated Signaling Pathways

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DOI: 10.21522/TIJPH.2013.SE.25.01.Art008

Authors : Selvaraj Jayaraman, Vishnu Priya Veeraraghavan, Shalini Vadivel, Pranav Raaj R

Abstract:

Breast cancer is a significant global health challenge, requiring continuous exploration of new treatments. Asarone, a bioactive compound from the Acorus genus, shows promising anticancer properties but its effects on breast cancer cells are underexplored. This study investigates asarone's anticancer potential against breast cancer cell lines using in vitro and in silico approaches. Asarone's antioxidant activity was evaluated using DPPH radical scavenging assays, revealing a dose-dependent (25.56, 32.18, 47.73, 54.83 and 66.74%) effect on free radicals. MTT assays showed a dose-dependent decrease in cell viability, indicating asarone's cytotoxicity towards breast cancer cells. mRNA expression analysis showed that targeting apoptosis regulators such as Bax (1, 1.3, 1.52 fold change upregualtion) and Bad (1, 1.4, and 1.6 fold upregulation) gene expression demonstrated that asarone induces apoptosis via the intrinsic pathway. Additionally, asarone inhibited Akt mNRA (1, 0.6, and 0.4 fold change down regulation), caspase-3 (1, 1.4, and 1.7 upregulation) and cytochrome-c mRNA (1, 1.2 and 1,54 fold change upregulation) suggesting interference with key cancer progression pathways. Molecular docking studies predicted favorable binding interactions between asarone and crucial proteins involved in apoptosis and cell survival, including Bax, Bad, cytochrome c, caspase 3, and Akt. These findings collectively highlight the multifaceted anticancer mechanisms of asarone against breast cancer cells. This study underscores the potential of asarone as a natural therapeutic agent for breast cancer, offering avenues for further exploration in translational research and clinical trials. The current study significantly advances our understanding of asarone's anticancer properties, offering promising directions for developing new and effective breast cancer therapies.

References:

[1].  Alkabban, F. M., Ferguson, T., 2022, Breast Cancer. In: StatPearls. Treasure Island (FL): StatPearls Publishing; September 26.

[2].  Jayaraman, S., Raj Natarajan, S., Ponnusamy, B., Veeraraghavan, V.P., Jasmine, S., 2023, Unlocking the potential of beta sitosterol: Augmenting the suppression of oral cancer cells through extrinsic and intrinsic signalling mechanisms. Saudi Dent J,35(8):1007-1013. doi: 10.1016/j.sdentj.2023.08.003.

[3].  Janani, K. S., Gayatri Devi, R., Selvaraj, J., 2022, Antiproliferative effect of Merremia emarginata (Burm. F.) leaf extract on SAOS-2 cell line. J Pharm Negat Results, 13:1805-1810. doi:10.47750/pnr.2022.13.S06237.

[4].  JinJin, P., Yuqiang, Y., Selvaraj, J., Ponnulakshmi, R., Prabhu Manickam, N,, Vidhya Rekha, U, Sridevi, G., Jeane Rebecca, R., Janaki, C. S., Dwarakesh, T., Chella Perumal., Monica, M., 2024, A review on advancements in the application of starch-based nanomaterials in biomedicine: Precision drug delivery and cancer therapy. International Journal of Biological Macromolecules, 26(1):130746.,https://doi.org/10.1016/j.ijbiomac.2024.130746.

[5].  Benedict, A., Suresh, V., Muthamizh, S., Jayaraman, S., & Hussein, M. A., 2024, Merremia emarginata Extract Potentiating the Inhibition of Human Colon Cancer Cells (HT-29) via the Modulation of Caspase-3/Bcl-2 Mediated Pathways. Curēus, https://doi.org/10.7759/cureus.56300.

[6].  Roy, J. R., Janaki, C. S., Jayaraman, S., Veeraraghavan, V. P., Periyasamy, V., Balaji, T., Vijayamalathi, M., Bhuvaneswari, P., Swetha, P., 2023, Hypoglycemic Potential of Carica Papaya in Liver Is Mediated through IRS-2/PI3K/SREBP-1c/GLUT2 Signaling in High-Fat-Diet-Induced Type-2 Diabetic Male Rats. Toxics, 11(3):240. doi: 10.3390/toxics11030240.

[7].  Butti, R., Das, S., Gunasekaran, V.P., Yadav, A.S., Kumar, D., Kundu, G.C., 2018, Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges. Mol Cancer,17(1):34. doi:10.1186/s12943-018-0797-x.

[8].  Chellian, R., Pandy, V., Mohamed, Z., 2017, Pharmacology and toxicology of α- and β-Asarone: A review of preclinical evidence. Phytomedicine, 32:41-58. doi:10.1016/j.phymed.2017.04.003

[9].  Hatano, T., Edamatsu, R., Hiramatsu, M., MORI, A., Fujita, Y., Yasuhara, T., OKUDA, T., 1989, Effects of the interaction of tannins with co-existing substances. VI.: effects of tannins and related polyphenols on superoxide anion radical, and on 1, 1-Diphenyl-2-picrylhydrazyl radical. Chemical and Pharmaceutical Bulletin37(8):2016-2021.

[10]. Perumal, S., Langeshwaran, K., Selvaraj, J., Ponnulakshmi, R., Shyamaladevi, B., Balasubramanian, M. P., 2018, Effect of diosmin on apoptotic signaling molecules in N-nitrosodiethylamine-induced hepatocellular carcinoma in experimental rats. Molecular and Cellular Biochemistry, 449: 27-37.

[11]. Zhang, X., Abdelrahman, A., Vollmar, B., & Zechner, D., 2018, The Ambivalent Function of YAP in Apoptosis and Cancer. International journal of molecular sciences, 19(12), 3770. https://doi.org/10.3390/ijms19123770.

[12]. Ramalingam, K., Yadalam, P. K., Ramani, P., Krishna, M., Hafedh, S., Badnjević, A., Cervino, G., & Minervini, G., 2024, Light gradient boosting-based prediction of quality of life among oral cancer-treated patients. BMC oral health, 24(1), 349. https://doi.org/10.1186/s12903-024-04050-x

[13]. Neralla, M., M, H., Preethi, A., Selvakumar, S. C., & Sekar, D., 2024, Expression levels of microRNA-7110 in oral squamous cell carcinoma. Minerva Dental and Oral Science, 73(3), 155–160. https://doi.org/10.23736/S2724-6329.23.04801-5

[14]. Prasad, M., Jayaraman, S., Rajagopal, P., Veeraraghavan, V. P., Kumar, P. K., Piramanayagam, S., Pari, L., 2022, Diosgenin inhibits ER stress-induced inflammation in aorta via iRhom2/TACE mediated signaling in experimental diabetic rats: An in vivo and in silico approach. Chem Biol Interact,358:109885. doi: 10.1016/j.cbi.2022.109885.

[15]. Kumar Subramanian, Aravind & Katyal, Deepika., 2023, The Effect of Topical Melatonin Gel on the oral health and salivary nickel and chromium content of orthodontic Patients: An In Vivo Study. World Journal of Dentistry. 14. 326-330. 10.5005/jp-journals-10015-2218.

[16]. Roy, J. R., Janaki, C. S., Jayaraman, S., Periyasamy, V., Balaji, T., Vijayamalathi, M., Veeraraghavan, V. P., 2022, Effect of Carica papaya on IRS-1/Akt signaling mechanisms in High-Fat-Diet–Streptozotocin-Induced type 2 diabetic experimental rats: a mechanistic approach. Nutrients, 14(19):4181.

[17]. Selvaraj, J., Veeraraghavan, V., Periyasamy, V., and Rajagopal, P., 2021., In Silico and in Vitro Study on the Inhibition of FtsZ Protein of Staphylococcus Aureus by Active Compounds from Andrographis Paniculata. Journal of Biologically Active Products from Nature, 11(2): 116–128. doi:10.1080/22311866.2021.1908163.

[18]. Ponnulakshmi, R., Shyamaladevi, B., Vijayalakshmi, P., & Selvaraj, J., 2019, In silico and in vivo analysis to identify the antidiabetic activity of beta sitosterol in adipose tissue of high fat diet and sucrose induced type-2 diabetic experimental rats. Toxicology Mechanisms and Methods, 29(4): 276–290. https://doi.org/10.1080/15376516.2018.1545815.

[19]. Babu, S., Jayaraman, S., 2020, An update on β-sitosterol: A potential herbal nutraceutical for diabetic management. Biomed Pharmacother, 131:110702. doi: 10.1016/j.biopha.2020.110702. Epub 2020 Aug 31. PMID: 32882583.

[20]. Guo, J., Gan, C., Cheng, B., Cui, B., Yi, F., 2023, Exploration of binding mechanism of apigenin to pepsin: Spectroscopic analysis, molecular docking, enzyme activity and antioxidant assays. pectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 290:122281. doi:10.1016/j.saa.2022.122281.