Cytotoxicity anticancer activities of anastrozole against breast, liver hepatocellular, and prostate cancer cells
Abstract
Objectives: To investigate the cytotoxic effect of anastrozole on breast (MCF7), liver hepatocellular (HepG2), and prostate (PC3) cancer cells.
Methods: This is a prospective study. Anastrozole’s mechanism of apoptosis in living cells was also determined by high content screening (HCS) assay. Methylthiazol tetrazolium (MTT) assay was carried out at the Centre of Biotechnology Research’s, Al-Nahrain University, Baghdad, Iraq between July 2015 and October 2015. The HCS assay was performed at the Centre for Natural Product Research
and Drug Discovery, Department of Pharmacology,
Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia between November 2015 and February 2016.
Results: The most significant cytotoxic effect of anastrozole towards 3 cancer cell lines was obtained when its concentration was 400 µg/mL. The MCF7 cells were more sensitive to anastrozole compared with the HepG2 and PC-3 cells. There was a significant increase in membrane permeability, cytochrome c and nuclear intensity when anastrozole (200 µg/mL) was used compared with doxorubicin (20 µg/mL) as a standard. Also, there was a significant decrease in cell viability and mitochondrial membrane permeability when anastrozole (200 µg/mL) was used compared with positive control.
Conclusion: Anastrozole showed cytotoxic effects against the MCF7, HepG2, and PC3 cell lines as determined in-vitro by the MTT assay. The HCS technique also showed toxic effect towards MCF7. It is evident that anastrozole inhibits the aromatase enzyme preventing the aromatization mechanism; however, it has a toxic effect.
Saudi Med J 2017; Vol. 38 (4): 359-365
doi: 10.15537/smj.2017.4.17061
How to cite this article:
Hassan F, El-Hiti GA, Abd-Allateef M, Yousif E. Cytotoxicity anticancer activities of anastrozole against breast, liver hepatocellular, and prostate cancer cells. Saudi Med J. 2017 Apr;38(4):359-365. doi: 10.15537/smj.2017.4.17061.Keywords
References
Yamamoto M, Hosoda M, Nakano K, Jia S, Hatanaka KC, Takakuwa E, et al. P53 accumulation is a strong predictor of recurrence in estrogen receptor-positive breast cancer patients treated with aromatase inhibitors. Cancer Sci 2014; 105: 81-88.
Lauring L, Wolff AC. Evolving role of the estrogen receptor as a predictive biomarker: ESR1 mutational status and endocrine resistance in breast cancer. J Clin Oncol 2016; 34: 2950-2952.
Bao T, Rudek MA. The clinical pharmacology of anastrozole. Eur Oncol Haematol 2011; 7: 106-108.
Miller WR, Larionov AA. Understanding the mechanisms of aromatase inhibitor resistance. Breast Cancer Res 2012; 14; 201.
Kümler I, Knoop AS, Jessing CAR, Ejlertsen B, Nielsen DL. Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant. ESMO Open-Cancer Horizons 2016; 1: e000062.
Dahir M, Travers-Gustafson D. Breast cancer, aromatase inhibitor therapy, and sexual functioning: a pilot study of the effects of vaginal testosterone therapy. Sex Med 2014; 2: 8-15.
Das M, Manna K. Chalcone scaffold in anticancer armamentarium: A molecular insight. J Toxicol 2016; 7651047.
American Cancer Society. Global Cancer Facts and Figures. 2nd ed. Atlanta (GA): American Cancer Society, USA; 2011.
Alison MR. Cancer, Encyclopedia of life sciences. Nature Publishing Group; 2011.
Peter ME. Programmed cell death: apoptosis meets necrosis. Nature 2011; 471: 310-312.
Eaton SR, Mazuski JE. Overview of severe clostridium difficile infection. Critical Care Clinics 2013; 29: 827-839.
Muthigi A, George AK, Brancato SJ, Agarwal, PK. Novel immunotherapeutic approaches to the treatment of urothelial carcinoma. Ther Adv Urol 2016; 8: 203-214.
Wellington KW. Understanding cancer and the anticancer activities of naphthoquinones – a review. RSC Adv 2015; 5: 20309−20338.
Skandarajah A. Cancer Council Australia Oncology Education Committee. In: Sabesan S, Olver I, editors. Principles of cancer surgery. Sydney (Australia): Cancer Council Australia; 2014.
Price P, Sikora K. Treatment of Cancer. 6th ed. FL, USA, CRC Press; 2014.
Saraswathy M, Gong S. Different strategies to overcome multidrug resistance in cancer. Biotechnol Adv 2013; 31: 1397−1407.
IRSA, Radiation Therapy. [Accessed 2016 September 1]. Available form: http://www.irsa.org/radation_therapy.html. 18. Abd-Allateef M, Hassan FA-A, Saleh WA. Study the effect of anastrozole on estradiol and aromatase enzyme in postmenopausal breast cancer patients. J Al-Nahrain Univ 2016; 19: 43−50.
Abdel-Megeed MF, Badr BE, Azaam MM, El-Hiti GA. Synthesis, antimicrobial and anticancer activities of a novel series of diphenyl 1-(pyridin-3-yl)ethylphosphonates. Bioorg Med Chem 2012; 20: 2252-2258.
Sweeney EE, McDaniel RE, Maximov PY, Fan P, Jordan VC. Models and mechanisms of acquired antihormone resistance in breast cancer: significant clinical progress despite limitations. Horm Mol Biol Clin Investig 2012; 9: 143-163.
Hole S, Pedersen A, Hasen S, Lundqvist J, Yde CW, Lykkesfeldt AE. New cell culture model for aromatase inhibitor-resistant breast cancer shows sensitivity to fulvestrant treatment and cross-resistance between letrozole and exemestane. Int J Oncol 2015; 46: 1481-1490.
Duellman SJ, Zhou W, Meisenheimer P, Vidugiris G, Cali JJ, Gautam P, et al. Bioluminescent, Nonlytic, Real-Time Cell Viability Assay and Use in Inhibitor Screening. Assay Drug Dev Tech 2015; 13: 456-465.
Hassan F, Abdul-Hameed A, Alshanon A, Abdullah MB, Huri HZ, et al. Antitumor activity for gold(III) complex by high content screening technique (HCS) and cell viability assay. Asian J Biochem 2015; 10: 252-266.
Al-Jailawi MH, Nasir HM, Aziz GM. Cytotoxic effect of biosurfactants produced by novel thermophillic Geobacillus thermoleovorans (JQ 912239). Int J Adv Res 2015; 3: 632-637.
Ingle JN, Kalari KR, Buzdar AU, Robson ME, Goetz MP, Desta Z, et al. Estrogens and their precursors in postmenopausal women with early breast cancer receiving anastrozole. Steroids 2015; 99: 32-83.
Topcul M, Cetin I, Ozlem KOM. The effects of anastrozole on the proliferation of FM3A cells. J BUON 2013; 18: 874-878.
Arimidex (Anastrozole) Tablet: AstraZeneca Pharmaceuticals LP. USA, Astrazeneca 2016. Available from: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=5257
Stoddart M. J. Cell viability assays: introduction. Methods Mol Biol 2011; 740: 1-6.
In: Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ, et al, editors. Assay Guidance Manual: Cell Viability Assays, In: Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences, 2013. editors Available from: https://www.ncbi.nlm.nih.gov/books/NBK53196/
Dive C, Watson JV, Workman, P. Multiparametric analysis of cell membrane permeability by two colour flow cytometry with complementary fluorescent probes. Cytometry 1990, 11: 244-252.
Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int 2011; 79: 33-45.
Wang Y-H, Xuan Z-H, Tian S, He G-R, Du G-H. Myricitrin attenuates 6-hydroxydopamine-induced mitochondrial damage and apoptosis in PC12 cells via inhibition of mitochondrial oxidation. J Funct Foods 2013; 5: 337-345.
Kim R, Emi M, Tanabe K. Role of mitochondria as the gardens of cell death. Cancer Chemother Pharmacol 2006; 57: 545-553.
Kilbride SM, Prehn JHM. Central roles of apoptotic proteins in mitochondrial function. Oncogene 2013; 32: 2703-2711.
Refbacks
- There are currently no refbacks.
Saudi Medical Journal is copyright under the Berne Convention and the International Copyright Convention. Saudi Medical Journal is an Open Access journal and articles published are distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC). Readers may copy, distribute, and display the work for non-commercial purposes with the proper citation of the original work. Electronic ISSN 1658-3175. Print ISSN 0379-5284.