Genistein Inhibits the Growth of AKR1C3 Anti-castration Resistance Prostate Cancer and Its Mechanism

CHEN Jin; FU Tianyu; LIU Jiang; ZHOU Hengping; SUN Yongxia; CHEN Siqi; AI li; ZHU Yanfeng

doi:10.13386/j.issn1002-0306.2021020001

Volume 42 Issue 22

Nov. 2021

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Science and Technology of Food Industry > 2021 > 42(22): 350-354. > DOI: 10.13386/j.issn1002-0306.2021020001

CHEN Jin, FU Tianyu, LIU Jiang, et al. Genistein Inhibits the Growth of AKR1C3 Anti-castration Resistance Prostate Cancer and Its Mechanism[J]. Science and Technology of Food Industry, 2021, 42(22): 350−354. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2021020001.

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Genistein Inhibits the Growth of AKR1C3 Anti-castration Resistance Prostate Cancer and Its Mechanism

Department of Public Health, Chengdu Medical College, Chengdu 610500, China

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Received Date: February 01, 2021
Available Online: September 12, 2021

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Abstract

Objective: To study the inhibition of akr1c3 expression by phytoestrogen genistein(Gen), thereby inhibiting the growth of castration-resistant prostate cancer(CRPC), and provide a theoretical basis for the clinical treatment of CRPC with genistein. Methods: 22RV1, VCaP, RWPE-1 cells were cultured in a hormone-free serum environment, and treated with different concentrations (0, 12.5, 25, 50, 100) μmol/L of GEN for 48 h. CCK-8 was used to detect cell proliferation activity. AKR1C3 siRNA and AKR1C3 inhibitor(ASP-9521) were combined with GEN to interfere with 22RV1 and VCaP cells, respectively, and the expression levels of PSA and AKR1C3 proteins in the cells were detected by Western blot. Results: Genistein could inhibit castration and resist the growth of prostate cancer. Western blot results showed that GEN could inhibit the expression of PSA and AKR1C3 proteins, and when combined with AKR1C3 siRNA and AKR1C3 inhibitor (ASP-9521), the inhibitory effect on AKR1C3 was more significant. Conclusion: Genistein expression in prostate cancer cells can resist by inhibiting AKR1C3 castration, thereby inhibiting cell proliferation CRPC.

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References

[1]	ATAN A, TUNCEL A, YESIL S, et al. Serum testosterone level, testosterone replacement treatment, and prostate cancer[J]. Advances in Urology,2013,2013(1):275945.
[2]	BAHMAD H F, SAMMAN H, MONZER A, et al. The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem-like cells[J]. Molecular Carcinogenesis,2019,58(7):1208−1220.
[3]	ZILLI T, DAL PRA A, KOUNTOURI M, et al. Prognostic value of biochemical response to neoadjuvant androgen deprivation before external beam radiotherapy for prostate cancer: A systematic review of the literature[J]. Cancer Treatment Reviews,2016,46:35−41. doi: 10.1016/j.ctrv.2016.03.016
[4]	BERLIN A, FERNÁNDEZ M I. Advances in the treatment of castration-resistant prostate cancer: Emphasis in new hormonal therapies[J]. Revista médica de Chile,2015,143(2):223−236.
[5]	LEE D J, CHA E K, DUBIN J M, et al. Novel therapeutics for the management of castration-resistant prostate cancer (CRPC)[J]. BJU International,2012,109(7):968−985. doi: 10.1111/j.1464-410X.2011.10643.x
[6]	TIAN Y, ZHAO L, WANG Y, et al. Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells[J]. Asian Journal of Andrology,2016,18(4):607−612. doi: 10.4103/1008-682X.169997
[7]	SÁNCHEZ B G, BORT A, MATEOS-GÓMEZ P A, et al. Combination of the natural product capsaicin and docetaxel synergistically kills human prostate cancer cells through the metabolic regulator AMP-activated kinase[J]. Cancer Cell International,2019,19(1):54. doi: 10.1186/s12935-019-0769-2
[8]	ZHENG X, JIANG Z, LI X, et al. Screening, synthesis, crystal structure, and molecular basis of 6-amino-4-phenyl-1, 4-dihydropyrano[2, 3-c]pyrazole-5-carbonitriles as novel AKR1C3 inhibitors[J]. Bioorganic & Medicinal Chemistry,2018,26(22):5934−5943.
[9]	PRELAJ A, REBUZZI S E, BUZZACCHINO F, et al. Radium-223 in patients with metastatic castration-resistant prostate cancer: Efficacy and safety in clinical practice[J]. Oncology Lerrers,2019,17(2):1467−1476.
[10]	HAMID A R, PFEIFFER M J, VERHAEGH G W, et al. Aldo-keto reductase family 1 member C3 (AKR1C3) is a biomarker and therapeutic target for castration-resistant prostate cancer[J]. Molecular Medicine,2013,18(1):1449−1455.
[11]	KARUNASINGHE N, MASTERS J, FLANAGAN J U, et al. Influence of aldo-keto reductase 1C3 in prostate cancer-A mini review[J]. Current Cancer Drug Targets,2017,17(7):603−616.
[12]	DOBBS R W, MALHOTRA N R, GREENWALD D T, et al. Estrogens and prostate cancer[J]. Prostate Cancer and Prostatic Diseases,2019,22(2):185−194. doi: 10.1038/s41391-018-0081-6
[13]	PFEIFFER M J, SMIT F P, SEDELAAR J P, et al. Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer[J]. Molecular Medicine,2011,17(7-8):657−664. doi: 10.2119/molmed.2010.00143
[14]	CHEN J, YANG Y, XU D, et al. Mesoporous silica nanoparticles combined with AKR1C3 siRNA inhibited the growth of castration-resistant prostate cancer by suppressing androgen synthesis in vitro and in vivo[J]. Biochem Biophys Res Commun,2021,540:83−89. doi: 10.1016/j.bbrc.2020.11.074
[15]	PENNING T M. AKR1C3 (type 5 17β-hydroxysteroid dehydrogenase/prostaglandin F synthase): Roles in malignancy and endocrine disorders[J]. Molecular and Cellular Endocrinology,2019,489:82−91. doi: 10.1016/j.mce.2018.07.002
[16]	HOFLAND J, VAN WEERDEN W M, DITS N F, et al. Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer[J]. Cancer Research,2010,70(3):1256−1264. doi: 10.1158/0008-5472.CAN-09-2092
[17]	LI C, ZHAO Y, ZHENG X, et al. In vitro CAPE inhibitory activity towards human AKR1C3 and the molecular basis[J]. Chemico-Biological Interactions,2016,253:60−65. doi: 10.1016/j.cbi.2016.05.012
[18]	PIPPIONE A C, GIRAUDO A, BONANNI D, et al. Hydroxytriazole derivatives as potent and selective aldo-keto reductase 1C3(AKR1C3) inhibitors discovered by bioisosteric scaffold hopping approach[J]. European Journal of Medical Chemistry,2017,139:936−946. doi: 10.1016/j.ejmech.2017.08.046
[19]	MUKUND V, MUKUND D, SHARMA V, et al. Genistein: Its role in metabolic diseases and cancer[J]. Critical Reviews in Oncology Hematology,2017,119:13−22. doi: 10.1016/j.critrevonc.2017.09.004
[20]	SUN G, ZHANG X, CHEN J, et al. What kind of patients with castration-naïve prostate cancer can benefit from upfront docetaxel and abiraterone: A systematic review and a network meta-analysis[J]. Urologic Oncology,2018,36(12):505−517. doi: 10.1016/j.urolonc.2018.09.005
[21]	MAILIN G, SHEN L, WANG S, et al. Genistein inhibits high fat diet-induced obesity through miR-222 by targeting BTG2 and adipor1[J]. Food Funct,2020,11(3):2418−2426. doi: 10.1039/C9FO00861F
[22]	LU Y, ZHAO A, WU Y, et al. Soybean soluble polysaccharides enhance bioavailability of genistein and its prevention against obesity and metabolic syndrome of mice with chronic high fat consumption[J]. Food Funct,2019,10(7):4153−4165. doi: 10.1039/C8FO02379D
[23]	ROCHIGNEUX P, SCHLEINITZ N, EBBO M, et al. Acute myositis: An unusual and severe side effect of docetaxel: A case report and literature review[J]. Anticancer Drugs,2018,29(5):477−481. doi: 10.1097/CAD.0000000000000620
[24]	ZHENG N, WANG L, HOU Y, et al. Rottlerin inhibits cell growth and invasion via down-regulation of EZH2 in prostate cancer[J]. Cell Cycle,2018,17(21-22):2460−2473. doi: 10.1080/15384101.2018.1542897
[25]	CHEN C, WANG Y, CHEN S, et al. Genistein inhibits migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways[J]. Taiwan J Obstet Gynecol,2020,59(3):403−408. doi: 10.1016/j.tjog.2020.03.012
[26]	LI F, ZHU Y F, CHEN J Y, et al. Effects of genistein on proliferation of castrate-resistant prostate cancer 22RV1 cells[J]. Journal of Zhengzhou University(Medical Sciences),2017,52(4):393−398.
[27]	SHAFIEE G, SAIDIJAM M, TAYEBINIA H, et al. Beneficial effects of genistein in suppression of proliferation, inhibition of metastasis, and induction of apoptosis in PC3 prostate cancer cells[J]. Archives of Physiology and Biochemistry,2020:1−9.
[28]	MORADI A, SRINIVASAN S, CLEMENTS J, et al. Beyond the biomarker role: Prostate-specific antigen(PSA) in the prostate cancer microenvironment[J]. Cancer Metastasis Rev,2019,38(3):333−346. doi: 10.1007/s10555-019-09815-3
[29]	LIU Y, HE S, CHEN Y, et al. Overview of AKR1C3: Inhibitor achievements and disease insights[J]. Journal of Medical Chemistry,2020,63(20):11305−11329. doi: 10.1021/acs.jmedchem.9b02138
[30]	BATRA N, SAM A, WOLDEMARIAM T, et al. Genistein combined polysaccharide(GCP) can inhibit intracrine androgen synthesis in prostate cancer cells[J]. Biomedicines,2020,8(8):282. doi: 10.3390/biomedicines8080282

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