Amygdalin Blocks Bladder Cancer Cell Growth in Vitro by Diminishing Cyclin A and Cdk2

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Aug 20

PMID 25136960

Citations 29

Authors

Jasmina Makarevic

Jochen Rutz

Eva Juengel

Silke Kaulfuss

Michael Reiter

Igor Tsaur

Georg Bartsch

Axel Haferkamp

Roman A Blaheta

Affiliations

Soon will be listed here.

Abstract

Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.

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References

Mundhenk J, Hennenlotter J, Zug L, Alloussi S, Todenhoefer T, Gakis G . Evidence for PTEN-independent Akt activation and Akt-independent p27(Kip1) expression in advanced bladder cancer. Oncol Lett. 2012; 2(6):1089-1093. PMC: 3406569. DOI: 10.3892/ol.2011.374. View

Gillett J, Ientile C, Hiscock J, Plank A, Martin J . Complementary and alternative medicine use in radiotherapy: what are patients using?. J Altern Complement Med. 2012; 18(11):1014-20. DOI: 10.1089/acm.2011.0334. View

Gupta S, Hau A, Beach J, Harwalker J, Mantuano E, Gonias S . Mammalian target of rapamycin complex 2 (mTORC2) is a critical determinant of bladder cancer invasion. PLoS One. 2013; 8(11):e81081. PMC: 3842329. DOI: 10.1371/journal.pone.0081081. View

Edwards B, Ward E, Kohler B, Eheman C, Zauber A, Anderson R . Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2009; 116(3):544-73. PMC: 3619726. DOI: 10.1002/cncr.24760. View

Boss D, Schwartz G, Middleton M, Amakye D, Swaisland H, Midgley R . Safety, tolerability, pharmacokinetics and pharmacodynamics of the oral cyclin-dependent kinase inhibitor AZD5438 when administered at intermittent and continuous dosing schedules in patients with advanced solid tumours. Ann Oncol. 2009; 21(4):884-894. PMC: 2844945. DOI: 10.1093/annonc/mdp377. View

Moss R . Patient perspectives: Tijuana cancer clinics in the post-NAFTA era. Integr Cancer Ther. 2005; 4(1):65-86. DOI: 10.1177/1534735404273918. View

Mirmiranpour H, Khaghani S, Zandieh A, Khalilzadeh O, Gerayesh-Nejad S, Morteza A . Amygdalin inhibits angiogenesis in the cultured endothelial cells of diabetic rats. Indian J Pathol Microbiol. 2012; 55(2):211-4. DOI: 10.4103/0377-4929.97874. View

Citrin D, Bloom D, Grutsch J, Mortensen S, Lis C . Beliefs and perceptions of women with newly diagnosed breast cancer who refused conventional treatment in favor of alternative therapies. Oncologist. 2012; 17(5):607-12. PMC: 3360900. DOI: 10.1634/theoncologist.2011-0468. View

Juengel E, Makarevic J, Tsaur I, Bartsch G, Nelson K, Haferkamp A . Resistance after chronic application of the HDAC-inhibitor valproic acid is associated with elevated Akt activation in renal cell carcinoma in vivo. PLoS One. 2013; 8(1):e53100. PMC: 3553088. DOI: 10.1371/journal.pone.0053100. View

10.

Kwon H, Hong S, Hahn D, Kim J . Apoptosis induction of Persicae Semen extract in human promyelocytic leukemia (HL-60) cells. Arch Pharm Res. 2003; 26(2):157-61. DOI: 10.1007/BF02976663. View

11.

Liang P, Li W, Wang Y, Wu T, Wu W, Liao A . HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma. BMC Cancer. 2012; 12:611. PMC: 3571926. DOI: 10.1186/1471-2407-12-611. View

12.

Rabbani F, Koppie T, Charytonowicz E, Drobnjak M, Bochner B, Cordon-Cardo C . Prognostic significance of p27Kip1 expression in bladder cancer. BJU Int. 2007; 100(2):259-63. DOI: 10.1111/j.1464-410X.2007.06927.x. View

13.

Canavese M, Santo L, Raje N . Cyclin dependent kinases in cancer: potential for therapeutic intervention. Cancer Biol Ther. 2012; 13(7):451-7. DOI: 10.4161/cbt.19589. View

14.

Lohberger B, Rinner B, Stuendl N, Kaltenegger H, Steinecker-Frohnwieser B, Bernhart E . Sesquiterpene lactones downregulate G2/M cell cycle regulator proteins and affect the invasive potential of human soft tissue sarcoma cells. PLoS One. 2013; 8(6):e66300. PMC: 3682952. DOI: 10.1371/journal.pone.0066300. View

15.

Gogolin S, Ehemann V, Becker G, Brueckner L, Dreidax D, Bannert S . CDK4 inhibition restores G(1)-S arrest in MYCN-amplified neuroblastoma cells in the context of doxorubicin-induced DNA damage. Cell Cycle. 2013; 12(7):1091-104. PMC: 3646865. DOI: 10.4161/cc.24091. View

16.

Huebner J, Micke O, Muecke R, Buentzel J, Prott F, Kleeberg U . User rate of complementary and alternative medicine (CAM) of patients visiting a counseling facility for CAM of a German comprehensive cancer center. Anticancer Res. 2014; 34(2):943-8. View

17.

Tang Y, Simoneau A, Liao W, Yi G, Hope C, Liu F . WIF1, a Wnt pathway inhibitor, regulates SKP2 and c-myc expression leading to G1 arrest and growth inhibition of human invasive urinary bladder cancer cells. Mol Cancer Ther. 2009; 8(2):458-68. PMC: 2768341. DOI: 10.1158/1535-7163.MCT-08-0885. View

18.

Merrick K, Larochelle S, Zhang C, Allen J, Shokat K, Fisher R . Distinct activation pathways confer cyclin-binding specificity on Cdk1 and Cdk2 in human cells. Mol Cell. 2008; 32(5):662-72. PMC: 2643088. DOI: 10.1016/j.molcel.2008.10.022. View

19.

MOERTEL C, Fleming T, Rubin J, Kvols L, Sarna G, Koch R . A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. N Engl J Med. 1982; 306(4):201-6. DOI: 10.1056/NEJM198201283060403. View

20.

Chen Y, Ma J, Wang F, Hu J, Cui A, Wei C . Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells. Immunopharmacol Immunotoxicol. 2012; 35(1):43-51. DOI: 10.3109/08923973.2012.738688. View