Document Type : Original Article(s)
Authors
- Abduladheem AL-Attabi 1
- Mohammed Sabah Mohammed 2
- Noor Ali Yazi AL-Khazali 3
- Sami Awad Alkubaisy 4
- Muna S. Merza 5
- Mohanad Ali Abdulhadi 6
- Yasser Fakri Mustafa 7
1 College of Medicine, University of Thi-Qar, Al-Nasiriyah, Iraq
2 Department of Medical Laboratory Techniques, Al-Maarif University College, Al-Anbar Governorate, Ramadi City, Iraq
3 Department of Medical Laboratory Techniques, Al-Safwa University College, Karbala, Iraq
4 Desert Studies Center, University of Anbar, Al-Anbar, Iraq
5 Prosthetic Dental Techniques Department, Al-Mustaqbal, University College, Hillah, Babylon, Iraq
6 Department of Biochemistry, College of Medicine, University of Anbar, Al-Anbar Governorate, Ramadi City, Iraq
7 Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, Iraq
Abstract
Background: Medicinal plants, predominantly those rich in polyphenolic mixtures, have been recommended to have chemopreventive and chemotherapeutic effects. This study aimed to investigate the effects of Urtica dioica L. extract (UDE) on angiogenesis and prostate cancer (PCa) cell progression through the phosphoinositide 3-kinase/Protein kinase B/ endothelial nitric oxide synthase (PI3K/AKT/eNOS) signaling pathway.
Method: This study employed an in vitro experimental design using PCa cell lines. To gain mechanistic insights into the anti-proliferative properties of UDE, PCa cell proliferation was assessed using an MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay in DU-145 cells (incubated for 48h). Also, we explored expression patterns of PI3K/AKT/eNOS pathway genes with therapeutic potential (with 50 µg/ml of UDE) in DU-145 cells by quantitative polymerase chain reaction and western blotting assay. Furthermore, we applied the ELISA cell death assay kit to reveal the apoptotic effects of UDE on PCa cells. Statistical analysis was determined using the Mann-Whitney U test and P ≤ 0.05 was considered statistically significant.
Results: UDE significantly decreased the cell viability after 48 h of treatment in DU-145 cells. Also, reducing the vascular endothelial growth factor (VEGF) levels revealed anti-angiogenic outcomes. Also, the eNOS level in the PI3K/AKT/eNOS pathway is dramatically alleviated upon treatment with UDE. Moreover, the apoptosis rate of DU-145 cells was enhanced compared with the control group.
Conclusion: The antitumoral activity of UDE was prominent in its persuasive anti-angiogenic potential, as UDE contributed to a striking diminish in PI3K/AKT/eNOS pathway in PCa and diminished the VEGF expression.
Highlights
Abduladheem AL-Attabi (Google Scholar)
Keywords
Main Subjects
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.30476/mejc.2024.102467.2086
- Miller KD, Nogueira L, Devasia T, Mariotto AB, Yabroff KR, Jemal A, et al. Cancer treatment and survivorship statistics, 2022. CA Cancer J Clin. 2022;72(5):409-36. doi: 10.3322/caac.21731PMID: 35736631.
- Targhazeh N, Yousefi B, Asghari S, Mohammadnejhad R, Mansouri P, Valizadeh A. MiR-622 acts as a tumor suppressor to induce cell apoptosis and inhibit metastasis in human prostate cancer. Andrologia. 2021;53(9):e14174. doi: 10.1111/and.14174. PMID: 34231241.
- Gould Rothberg BE, Quest TE, Yeung SJ, Pelosof LC, Gerber DE, Seltzer JA, et al. Oncologic emergencies and urgencies: A comprehensive review. CA Cancer J Clin. 2022;72(6):570-93. doi: 10.3322/caac.21727. PMID: 35653456.
- Giri VN, Morgan TM, Morris DS, Berchuck JE, Hyatt C, Taplin ME. Genetic testing in prostate cancer management: Considerations informing primary care. CA Cancer J Clin. 2022;72(4):360-71. doi: 10.3322/caac.21720. PMID: 35201622.
- Khan F, Pandey P, Jha NK, Jafri A, Khan I. Anti-proliferative effect of Moringa oleifera methanolic leaf extract by down-regulation of Notch signaling in DU145 prostate cancer cells. Gene Reports. 2020;34:100619. doi:10.1016/j.genrep.2020.100619.
- Ahmed SI, Sarwar S, Verma H, Lakkireddy C, Adil MAM, Khan AA, et al. Implication of circulating microRNA-21 as a potential non-invasive diagnostic predictor of prostate cancer patients. Human Gene. 2022;34: 201081. doi: 10.1016/j.humgen.2022.201081.
- Wong HY, Sheng Q, Hesterberg AB, Croessmann S, Rios BL, Giri K, et al. Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease. Nat Commun. 2022;13(1):6036. doi: 10.1038/s41467-022-33780-1. PMID: 36229464; PMCID: PMC9562361.
- Al-Marzook FA, Hassan DM, Alghazal MW, Kadheem RAA, Jalil AT, Saleh MM. MicroRNA-32 suppression: its effects on prostate cancer cells' capability to proliferate and migrate. Drug Res (Stuttg). 2023;73(3):170-4. doi: 10.1055/a-1977-8848. PMID: 36626918.
- Chung MS, Bae WJ, Choi SW, Lee KW, Jeong HC, Bashraheel F, et al. An Asian traditional herbal complex containing Houttuynia cordata Thunb, Perilla frutescens Var. acuta and green tea stimulates hair growth in mice. BMC Complement Altern Med. 2017;17(1):515. doi: 10.1186/s12906-017-2003-x. PMID: 29197368; PMCID: PMC5712091.
- Shehata MG, Abu-Serie MM, Abd El-Aziz NM, El-Sohaimy SA. Nutritional, phytochemical, and in vitro anticancer potential of sugar apple (Annona squamosa) fruits. Sci Rep. 2021;11(1):6224. doi: 10.1038/s41598-021-85772-8. PMID: 33737634; PMCID: PMC7973736.
- Esposito S, Bianco A, Russo R, Di Maro A, Isernia C, Pedone PV. Therapeutic perspectives of molecules from Urtica dioica extracts for cancer treatment. Molecules. 2019;24(15):2753. doi: 10.3390/molecules24152753. PMID: 31362429; PMCID: PMC6695697.
- Telo S, Halifeoglu I, Ozercan IH. Effects of stinging nettle (Urtica Dioica L.,) on antioxidant enzyme activities in rat model of mammary gland cancer. Iran J Pharm Res. 2017;16(Suppl):164-70. PMID: 29844787; PMCID: PMC5963657.
- Bhusal KK, Magar SK, Thapa R, Lamsal A, Bhandari S, Maharjan R, et al. Nutritional and pharmacological importance of stinging nettle (Urtica dioica L.): A review. Heliyon. 2022;8(6):e09717. doi: 10.1016/j.heliyon.2022.e09717. PMID: 35800714; PMCID: PMC9253158.
- Harrison F, Furner-Pardoe J, Connelly E. An assessment of the evidence for antibacterial activity of stinging nettle (Urtica dioica) extracts. Access Microbiol. 2022;4(3):000336. doi: 10.1099/acmi.0.000336. PMID: 35693473; PMCID: PMC9175978.
- Tavallali H, Bahmanzadegan A, Rowshan V, Tavallali V. Essential oil composition, antioxidant activity, phenolic compounds, total phenolic and flavonoid contents from pomace of citrus aurantifolia. Journal of Medicinal plants and By-Products. 2021; 10(Special): 103-16. doi: 10.22092/jmpb.2020.341476.1175
- Dar SA, Ganai FA, Yousuf AR, Balkhi MU, Bhat TM, Sharma P. Pharmacological and toxicological evaluation of Urtica dioica. Pharm Biol. 2013;51(2):170-80. doi: 10.3109/13880209.2012.715172. PMID: 23036051.
- El Haouari M, Rosado JA. Phytochemical, anti-diabetic and cardiovascular properties of Urtica dioica L. (Urticaceae): A review. Mini Rev Med Chem. 2019;19(1):63-71. doi: 10.2174/1389557518666180924121528. PMID: 30246639.
- Devkota HP, Paudel KR, Khanal S, Baral A, Panth N, Adhikari-Devkota A, et al. Stinging nettle (Urtica dioica L.): Nutritional composition, bioactive compounds, and food functional properties. Molecules. 2022;27(16):5219. doi: 10.3390/molecules27165219. PMID: 36014458; PMCID: PMC9413031.
- Mohammadi A, Mansoori B, Aghapour M, Baradaran B. Urtica dioica dichloromethane extract induce apoptosis from intrinsic pathway on human prostate cancer cells (PC3). Cell Mol Biol (Noisy-le-grand). 2016;62(3):78-83. PMID: 27064877.
- Sekhoacha M, Riet K, Motloung P, Gumenku L, Adegoke A, Mashele S. Prostate cancer review: Genetics, diagnosis, treatment options, and alternative approaches. Molecules. 2022;27(17):5730. doi: 10.3390/molecules27175730. PMID: 36080493; PMCID: PMC9457814.
- Siddique AB, Ebrahim HY, Tajmim A, King JA, Abdelwahed KS, Abd Elmageed ZY, et al. Oleocanthal attenuates metastatic castration-resistant prostate cancer progression and recurrence by targeting SMYD2. Cancers (Basel). 2022;14(14):3542. doi: 10.3390/cancers14143542. PMID: 35884603; PMCID: PMC9317016.
- Fazli J, Fattah K, Moliani A, Valizadeh A, Bazavar M. The expression of miR-181b, CYLD, CBX-7, BCL2, and p53 in osteosarcoma patients and correlation with clinicopathological factors. Chem Biol Drug Des. 2023;101(1):2-8. doi: 10.1111/cbdd.14144. PMID: 36098711.
- D'Abrosca B, Ciaramella V, Graziani V, Papaccio F, Della Corte CM, Potenza N, et al. Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis. Sci Rep. 2019;9(1):4986. doi: 10.1038/s41598-019-41372-1. PMID: 30899059; PMCID: PMC6428841.
- Ghasemi S, Moradzadeh M, Mousavi SH, Sadeghnia HR. Cytotoxic effects of Urtica dioica radix on human colon (HT29) and gastric (MKN45) cancer cells mediated through oxidative and apoptotic mechanisms. Cell Mol Biol (Noisy-le-grand). 2016;62(9):90-6. PMID: 27755943.
- Hodroj MH, Al Bast NAH, Taleb RI, Borjac J, Rizk S. Nettle tea inhibits growth of acute myeloid leukemia cells in vitro by promoting apoptosis. Nutrients. 2020;12(9):2629. doi: 10.3390/nu12092629. PMID: 32872275; PMCID: PMC7551597.
- Fattahi S, Ardekani AM, Zabihi E, Abedian Z, Mostafazadeh A, Pourbagher R, et al. Antioxidant and apoptotic effects of an aqueous extract of Urtica dioica on the MCF-7 human breast cancer cell line. Asian Pac J Cancer Prev. 2013;14(9):5317-23. doi: 10.7314/apjcp.2013.14.9.5317. PMID: 24175819.
- Liu ZL, Chen HH, Zheng LL, Sun LP, Shi L. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduct Target Ther. 2023;8(1):198. doi: 10.1038/s41392-023-01460-1. PMID: 37169756; PMCID: PMC10175505.
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