Adv Pharm Bull. 2019;9(3):453-461.
doi: 10.15171/apb.2019.054
  Abstract View: 81
  PDF Download: 54

Research Article

Cell Cycle Modulation of CHO-K1 Cells Under Genistein TreatmentCorrelates with Cells Senescence, Apoptosis and ROS Level but in aDose-Dependent Manner

Riris Istighfari Jenie 1,2 ORCiD, Nur Dina Amalina 2, Gagas Pradani Nur Ilmawati 2, Rohmad Yudi Utomo 1,2 ORCiD, Muthi Ikawati 1,2 ORCiD, Annisa Khumaira 2, Jun- Ya Kato 3, Edy Meiyanto 1,2 * ORCiD

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.
2 Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.
3 Laboratory of Tumor Cell Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, 630-0101, Japan.


Purpose: Genistein, a soy isoflavone, exhibits a biphasic effect on cells proliferation withsome different effects between ER-alpha and ER-beta. The objective of this present study is todetermine the modulatory effect based on cell cycle progression under genistein treatment incombination with 17-β estradiol (E2) on CHO-K1 cells.Methods: The effect of genistein 0.1-100 μM on cells proliferation was examined by MTT assay.The modulation of genistein and estradiol (E2) on cell cycle and apoptosis were observed byusing flowcytometry with PI and PI/AnnexinV staining, respectively. Moreover, the effect ofgenistein and E2 on senescence cells, and ROS level were determined by senescence-associatedβ-galactosidase (SA β-gal) staining and by using flowcytometry with 2’, 7’–dichlorofluorescindiacetate (DCFDA) staining, respectively. The expression level of the cell cycle and senescenceprotein markers were observed by immunoblotting.Results: Single treatment of genistein at physiologically achievable (low) concentration (<2 μM)induced proliferation of CHO-K1 cells while at a pharmacological (high) concentration (50 and100 μM) suppressed cells proliferation. Interestingly, treatment of genistein at the physiologicalconcentration in combination with E2 for 24, 48 and 72 h decreased cells viability on CHO-K1cells compared to untreated cells. Further analysis of the cells showed that 50 μM genisteininduced G2/M phase accumulation and induced apoptosis. Moreover, genistein induced cellsenescence and increased ROS level. Immunoblotting analysis showed the decreasing of ERalpha,Bcl2, and ppRb protein level upon treatment of 1 μM Gen and 1 nM E2.Conclusion: Our results suggest that the cell proliferation inhibitory mechanism of genistein atpharmacological concentration involved the induction of cell senescence, and the elevationof ROS level. Moreover, the decreased of cells proliferation upon treatment of physiologicalconcentration of genistein in combination with E2 may be correlated with the alteration of ERexpression.
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Submitted: 06 Oct 2018
Revised: 13 Feb 2019
Accepted: 14 Apr 2019
First published online: 01 Aug 2019
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