Recombinant human Erythropoietin enhanced the cytotoxic effects of tamoxifen toward the spheroid MCF-7 breast cancer cells |
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Authors: | Hareth Y Shujaa Edin Nagi A AL-Haj Abdullah Rasedee Noorjahan Banu Alitheen Arifah Abdul Kadir Chee Wun How Heshu Sulaiman Rahman Hussah Abdullah AL-Shwyeh |
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Institution: | 1. Institute of Bioscience, Universiti Putra Malaysia,Malaysia;2. Faculty of Medicine and Health Sciences, Sana’a University, Yemen;3. Faculty of Veterinary Medicine, Universiti Putra Malaysia, Malaysia;4. Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, Malaysia;5. School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia;6. College of Medicine, University of Sulaimani, Kurdistan Region, Iraq;7. Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University (IAU), Dammam 31441-1982, Saudi Arabia |
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Abstract: | Erythropoietin (EPO) is widely used to treat anemia in patients undergoing chemotherapy for cancers. The main objective of this study was to investigate the effect of rHuEPO on the response of spheroid breast cancer, MCF-7, cells to tamoxifen treatment. The MCF-7 spheroids were treated with 10 mg/mL tamoxifen in combination with either 0, 10, 100 or 200 IU/mL rHuEPO for 24, 48 or 72 h. The viability of the MCF-7 cells was determined using the annexin-V, cell cycle, caspases activation and acridine orange/propidium iodide staining. rHuEPO-tamoxifen combination significantly (p greater than 0.05) increased the number of spheroid MCF-7 cells entering early apoptotic phase after 12 h and late apoptotic phase after 24 h of treatment; primarily the result of the antiproliferative effect tamoxifen. Tamoxifen alone significantly (p < 0.05) increased the caspase-3 and ?9 activities in the spheroid MCF-7 cells by 200 to 550% of the control. Combination rHuEPO and tamoxifen produced much lesser effect on the caspase-8 activity. The rHuEPO in the combination treatment had concentration-dependently caused decrease in the caspase activities. rHuEPO-tamoxifen combination markedly increased MCF-7 cells entering the SubG0/G1 phase of the cell cycle by more than 500% of the control, while decreasing those entering the G2 + M and S phases by 50%. After 72 h, the combination treatment produced greater (p < 0.05) change in the SubG0/G1 phase than tamoxifen treatment alone. Morphologically, spheroid MCF-7 cells subjected to combination rHuEPO-tamoxifen treatment showed nuclear condensation and margination, cytoplasmic blebbing, necrosis, and early and late apoptosis. Thus, the study showed that rHuEPO-tamoxifen combination induced apoptosis in the spheroid MCF-7 cells. The apoptotic effect of the rHuEPO-tamoxifen combination treatment on the MCF-7 cells was greater than that produced by tamoxifen alone. The rHuEPO-tamoxifen treatment enhanced the caspase-independent apoptotic effects of tamoxifen on the spheroid MCF-7 cells. |
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Keywords: | Recombinant human erythropoietin Tamoxifen Spheroids Hanging drop Ultra-low adhesive plate Overlay technique rHuEPO"} {"#name":"keyword" "$":{"id":"k0040"} "$$":[{"#name":"text" "_":"Recombinant human erythropoietin TAM Tamoxifen ULAT"} {"#name":"keyword" "$":{"id":"k0050"} "$$":[{"#name":"text" "_":"ultra-low adhesive plate HD"} {"#name":"keyword" "$":{"id":"k0060"} "$$":[{"#name":"text" "_":"Hanging drop poly-HEMA"} {"#name":"keyword" "$":{"id":"k0070"} "$$":[{"#name":"text" "_":"Poly 2-hydroxyethyl methacrylate OLT"} {"#name":"keyword" "$":{"id":"k0080"} "$$":[{"#name":"text" "_":"Overlay technique MCF-7"} {"#name":"keyword" "$":{"id":"k0090"} "$$":[{"#name":"text" "_":"human breast cell line ESBR"} {"#name":"keyword" "$":{"id":"k0100"} "$$":[{"#name":"text" "_":"The Eppendorf swing-bucket rotor with tubes rack ECRB"} {"#name":"keyword" "$":{"id":"k0110"} "$$":[{"#name":"text" "_":"Eppendorf A-4-62 centrifuge rotor 1 MTP buckets MCF-7"} {"#name":"keyword" "$":{"id":"k0120"} "$$":[{"#name":"text" "_":"GMD geometrical mean diameter geometrical mean of diameter S"} {"#name":"keyword" "$":{"id":"k0140"} "$$":[{"#name":"text" "_":"surface area CC"} {"#name":"keyword" "$":{"id":"k0150"} "$$":[{"#name":"text" "_":"correlation coefficient CV"} {"#name":"keyword" "$":{"id":"k0160"} "$$":[{"#name":"text" "_":"coefficient of variance |
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