Effect of Adiantum capillus-veneris Extract on Expression of P16 and Bax in breast cancer (MCF-7) cell line
DOI:
https://doi.org/10.24237/04.04.693Keywords:
Adiantum capillus-veneris, p16 gene, Bax gene, (MCF-7) cell line.Breast cancerAbstract
Medical hebes are intriguing and have expanded as potential therapeutic agents against cancer cells. Plant extract identification is the most significant aerea of study in the world. In this research the extract of Adiantum capillus veneris L. (ACV).was prepared using an ethanolic solution.The toxicity of AVC was measured by MTT assay with different drug concentrations (1000,5000,250,65.5) ug/ml in MCF-7 breast cancer cell line for 24 hrs. P16 is a tumor suppressor protein , it slows down cell cycle by preventing from G1 phase to S phase. Bax gene plays an important role as an activator of apoptosis, its function is necessary for balance among the main apoptotic members Bcl2. P16 and Bax mRNA levels were detected by real time PCR PCR (qRT-PCR). The MTT results showed that 1746 ug/ml of ACV had 50% toxicity in MCF-7 after 24 hours of incubation. qRT-PCR results showed an increase of gene expression for P16 and Bax mRNA.
In conclusion: A significant increase overexpression of P16 and Bax was observed in MCF-7 cells induced by treating with ACV extract which may give a potential therapy to treat breast cancer by targeting the important genes in cell cycle and apoptosis.
Downloads
References
[1]
World Health Organization, WHO Bacterial Priority Pathogens List, 2024: Bacterial Pathogens of Public Health Importance, to Guide Research, Development, and Strategies to Prevent and Control Antimicrobial Resistance, Geneva, Switzerland: WHO, 2024.
[2]
J. Loscalzo, “Harrison’s Principles of Internal Medicine”, 2022nd ed. New York, NY, USA: McGraw Hill, (2022).
[3]
F. Mohammadizadeh, and F. Nasri, “P16 expression in human breast carcinoma and its relationship to clinicopathological parameters”, Advanced Biomedical Research, vol. 12, no. 1, p. 154(2023), DOI: 10.4103/abr.abr_180_22
[4]
X. Sheng, Y. Guo, and Y. Lu, “Prognostic role of methylated GSTP1, p16, ESR1 and PITX2 in patients with breast cancer: A systematic meta-analysis under the guideline of PRISMA”, Medicine, vol. 96, no. 28, p. e7476(2017), DOI: https://doi.org/10.1097/MD.0000000000007476 .
[5]
J. Ni, “p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases”, Nature Communications, vol. 13, no. 1, p. 1473(2022), DOI: https://doi.org/10.1038/s41467-022-29081-2 .
[6]
E. Peurala, P. Koivunen, K. M. Haapasaari, R. Bloigu, and A. Jukkola-Vuorinen, “The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer”, Breast Cancer Research, vol. 15, pp. 1–10(2013), DOI: 10.1186/bcr3376.
[7]
J. Krishnamurthy et al., “p16INK4a induces an age-dependent decline in islet regenerative potential,” Nature, vol. 443, no. 7110, pp. 453–457(2006), DOI: https://doi.org/10.1038/nature05092 .
[8]
D. N. Danforth Jr., “Genomic changes in normal breast tissue in women at normal risk or at high risk for breast cancer”, Breast Cancer: Basic and Clinical Research, vol. 10, pp. BCBCR-S39384, (2016), DOI: https://doi.org/10.4137/BCBCR.S39384.
[9]
M. Hassan, O. Feyen, and E. Grinstein, “Fas‐induced apoptosis of renal cell carcinoma is mediated by apoptosis signal‐regulating kinase 1 via mitochondrial damage‐dependent caspase‐8 activation”, Analytical Cellular Pathology, vol. 31, no. 6, pp. 437–456(2009), DOI: https://doi.org/10.3233/CLO-2009-0488
[10]
J. M. Adams, and S. Cory, “The Bcl-2 apoptotic switch in cancer development and therapy”, Oncogene, vol. 26, no. 9, pp. 1324–1337(2007), DOI: https://doi.org/10.1038/sj.onc.1210220
[11]
T. Khamis, “The antiproliferative activity of Adiantum pedatum extract and/or piceatannol in phenylhydrazine-induced colon cancer in male albino rats: the miR-145 expression of the PI-3K/Akt/p53 and Oct4/Sox2/Nanog pathways”, Molecules, vol. 28, no. 14, p. 5543(2023), DOI: https://doi.org/10.3390/molecules28145543.
[12]
S. K. Ibrahim, “Study the effect of Linum usitatissimum (flax seeds) and Eucalyptus rostrata (Eucalyptus) leaves extracts on Pseudomonas aeruginosa growth in vivo and in vitro”, Biochemical & Cellular Archives, vol. 20, no. 2, (2020).
[13]
H. Q. Hameed, A. A. Hasan, and R. M. Abdullah, “Effect of Olea europaea L. extraction and TiO₂ nanoparticles against Pseudomonas aeruginosa”, Indian Journal of Public Health Research & Development, vol. 10, no. 6, (2019).
[14]
A. M. A. Al-Shuwaikh, R. M. A. Al-Shwaikh, and J. S. Hassan, “Effect of Trigonella foenum extract and ZnO₂ nanoparticles on Some Pathogenic Fungi and Bacteria”, La Prensa Medica, 105(4), (2019).
[15]
T. A. Muhsen, S. N. Hawar, T. S. Mahdi, and R. Khaleel, “Effect of Eucalyptus and Myrtus extracts identification by gas chromatography-mass spectrometry on some species of Candida as a model of medical plants”, Annals of Tropical Medicine and Public Health, vol. 23, no. S10, pp. 1–11(2020).
[16]
O. Z. Al-Hayali, M. F. A. Marjani, and A. Maleki, “Evaluation of Rosmarinus officinalis leaves essential oils activity against vancomycin intermediate Staphylococcus aureus (VISA) isolated from Baghdad hospital patients”, Iraqi Journal of Science, pp. 2153–2167(2023), DOI: https://doi.org/10.24996/ijs.2023.64.5.5
[17]
K. K. Ghudhaib, and F. M. Khaleel, “Evaluation of antioxidants, antibacterial and antidiabetic activities of aqua-alcoholic marjoram extract”, Baghdad Science Journal, (2024),DOI: https://doi.org/10.21123/bsj.2024.9328
[18]
H. S. Al-Shmgani, Z. T. Alasady, E. M. Ali, and M. J. Al-Jassani, “Antioxidant, cytotoxicity and phytochemical analysis of Larinus maculates F. cocoon aqueous extract against lung cancer”, in Journal of Physics: Conference Series, vol. 1879, no. 2, p. 022025(2021), DOI: 10.1088/1755-1315/421/2/022025
[19]
S. M. Fathi, and I. A. Ali, “Cytotoxic effect of the alcoholic extract of Conocarpus erectus leaves on MDA-MB 231 and MCF7 breast cancer cell lines”, Iraqi Journal of Science, pp. 84–90(2023), DOI: https://doi.org/10.24996/ijs.2023.64.1.9.
[20]
Z. O. Salman, B. M. Alwash, and E. J. Kadhim, “Isolation and identification of flavonoid compounds from Euphorbia milii plant cultivated in Iraq and evaluation of its genetic effects on two types of cancer cell line”, Baghdad Science Journal, (2024), DOI: https://doi.org/10.21123/bsj.2024.9276
[21]
A. N. Khalaf, and I. J. Abed, “Evaluating the in vitro cytotoxicity of Thymus vulgaris essential oil on MCF-7 and HeLa cancer cell lines”, Iraqi Journal of Science, pp. 2862–2871(2021), DOI: https://doi.org/10.24996/ijs.2021.62.9.3.
[22]
C. Pan, “Phytochemical constituents and pharmacological activities of plants from the genus Adiantum: A review”, Tropical Journal of Pharmaceutical Research, vol. 10, no. 5, pp. 681–692(2011), DOI: https://doi.org/10.4314/tjpr.v10i5.18
[23]
J. Gruenwald, T. Brendler, and C. Jaenicke, PDR for Herbal Medicines. Montvale, NJ, USA: Medical Economics Company, (2008).
[24]
S. Rautray, S. Panikar, T. Amutha, and A. U. Rajananthini, “Anticancer activity of Adiantum capillus veneris and Pteris quadriureta L. in human breast cancer cell lines”, Molecular Biology Reports, vol. 45, no. 6, pp. 1897–1911(2018), DOI: https://doi.org/10.1007/s11033-018-4337-y
[25]
Y. C. Wong, M. Y. Ahmad-Mudzaqqir, and W. A. Wan-Nurdiyana, “Extraction of essential oil from cinnamon (Cinnamomum zeylanicum)”, Oriental Journal of Chemistry, vol. 30, no. 1, p. 37(2014), DOI: http://dx.doi.org/10.13005/ojc/300105.
[26]
M. I. Salman, M. A. Emran, and A. M. Al-Shammari, “Spheroid-formation 3D engineering model assay for in vitro assessment and expansion of cancer cells”, in AIP Conference Proceedings, vol. 2372, no. 1, (2021), DOI: https://doi.org/10.1063/5.0065362
[27]
T. Mosmann, “Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays”, Journal of Immunological Methods, vol. 65, no. 1–2, pp. 55–63(1983), DOI: https://doi.org/10.1016/0022-1759(83)90303-4.
[28]
S. Wu, and D. K. Shah, “Determination of ADC cytotoxicity in immortalized human cell lines”, in Antibody-Drug Conjugates: Methods and Protocols, pp. 329–340(2020), DOI: https://doi.org/10.1007/978-1-4939-9929-3_23
[29]
K. J. Livak, “User bulletin no. 2: ABI PRISM 7700 sequence detection system”, Applied Biosystems, Foster City, CA, USA, (2001), DOI: https://doi.org/10.1006/meth.2001.1262.
[30]
A. Allameh, A. Moazeni-Roodi, I. Harirchi, M. Ravanshad, M. Motiee-Langroudi, A. Garajei, A. Hamidavi, and S. A. Mesbah-Namin, “Promoter DNA methylation and mRNA expression level of p16 gene in oral squamous cell carcinoma: Correlation with clinicopathological characteristics”, Pathology & Oncology Research, vol. 25, no. 4, pp. 1535–1543(2019), DOI: https://doi.org/10.1007/s12253-018-0542-1
[31]
N. K. Rana, P. Singh, and B. Koch, "CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis", Biological Research, vol. 52, no. 1, p. 12, (2019), DOI: https://doi.org/10.1186/s40659-019-0221-z.
[32]
K. M. Yap, M. Sekar, C. R. Wu, S. H. Gan, S. R. Sani, M. K. Sahu, and Y. S. Wu, “Drug delivery of natural products through nanocarriers for effective breast cancer therapy: A comprehensive review of literature”, International Journal of Nanomedicine, vol. 16, pp. 7891–7941(2021), DOI: https://doi.org/10.2147/IJN.S328135.
[33]
A. Wahi, “Recent updates on nano-phyto-formulations based therapeutic intervention for cancer treatment”, Oncology Research, vol. 32, no. 1, p. 19(2023), DOI: https://doi.org/10.32604/or.2023.042228
[34]
M. K. Rana, A. P. S. Rana, and U. Khera, “Expression of p53 and p16 in carcinoma breast tissue: depicts prognostic significance or coincidence”, Cureus, vol. 13, no. 11, (2021), DOI: https://doi.org/10.7759/cureus.19395.
[35]
A. V. Lee, S. Oesterreich, and N. E. Davidson, “MCF-7 cells—changing the course of breast cancer research and care for 45 years”, Journal of the National Cancer Institute, vol. 107, no. 7, p. djv073(2015), DOI: https://doi.org/10.1093/jnci/djv073.
[36]
R. Vadi, V. Manisha, and K. Swati, “Hansraj (Adiantum capillus veneris Linn.): A systematic review on its ethnobotany, phytochemical and pharmacological profile”, International Journal of Ayurveda and Pharma Research, (2017).
[37]
Z. Ayoub, S. Malik, and A. Mehta, “In vitro and in vivo anti-cancer efficacy of Adiantum capillus-veneris L. against some selected human cancer cell lines and on Ehrlich ascites carcinoma mouse model”, Int. J. Pharm. Sci. Drug Res., vol. 12, pp. 267–274(2020), DOI: https://doi.org/10.25004/IJPSDR.2020.120309
[38]
S. Rautray, S. Panikar, T. Amutha, and A. U. Rajananthini, "Anticancer activity of Adiantum capillus veneris and Pteris quadriureta L. in human breast cancer cell lines", Molecular Biology Reports, vol. 45, no. 6, pp. 1897–1911(2018), DOI: https://doi.org/10.1007/s11033-018-4337-y
[39]
K. J. Van Zee, J. E. Calvano, and M. Bisogna, “Hypomethylation and increased gene expression of p16INK4a in primary and metastatic breast carcinoma as compared to normal breast tissue”, Oncogene, vol. 16, no. 21, pp. 2723–2727(1998), DOI: https://doi.org/10.1038/sj.onc.1201794
[40]
M. Li, “p16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis”, Journal of Cancer, vol. 11, no. 6, p. 1457(2020), DOI: https://doi.org/10.7150/jca.35479
[41]
M. Feriancova, I. Walter, C. F. Singer, J. Gazdarica, and K. Pohlodek, “Expression of COX-2, p16, and Ki67 in the range from normal breast tissue to breast cancer”, Neoplasma, vol. 68, no. 2, pp. 342–351(2021) , DOI: https://doi.org/10.4149/neo_2020_200731N798
[42]
Y. Tsujimoto and S. Shimizu, “Bcl-2 family: life-or-death switch”, FEBS Letters, vol. 466, no. 1, pp. 6–10(2000), DOI: https://doi.org/10.1016/S0014-5793(99)01761-5
[43]
M. Yadegari, S. Riahy, S. Mirdar, G. Hamidian, and P. Mosadegh Zavaragh, “Effect of the Adiantum capillus veneris extract on Bax and Bcl2 apoptotic markers of lung modulation in trained rats and exposed to hypoxic stress”, (2017).
[44]
N. Kazemi and S. B. Shahrestani, “Effect of saffron extract on expression of Bax and Bcl-2 genes in gastric adenocarcinoma cell line (AGS)”, Gene, Cell and Tissue, vol. 5, no. 3, (2018), DOI: https://doi.org/10.5812/gct.63608
[45]
T. Bagherian, S. H. Tackallou, and A. Mohammadgholi, “Quantitative measurement of Bax and Bcl2 genes and protein expression in MCF7 cell-line when treated by Aloe Vera extract”, Gene Reports, vol. 23, p. 101123(2021), DOI: https://doi.org/10.1016/j.genrep.2021.101123.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 CC BY 4.0
This work is licensed under a Creative Commons Attribution 4.0 International License.
