Withanolides from Aeroponically Grown Physalis Peruviana and Their Selective Cytotoxicity to Prostate Cancer and Renal Carcinoma Cells

Overview

Journal J Nat Prod

Date 2017 Jun 16

PMID 28617598

Citations 18

Authors

Ya-Ming Xu

E M Kithsiri Wijeratne

Ashley L Babyak

Hanna R Marks

Alan D Brooks

Poonam Tewary

Li-Jiang Xuan

Wen-Qiong Wang

Thomas J Sayers

A A Leslie Gunatilaka

Affiliations

Soon will be listed here.

Abstract

Investigation of aeroponically grown Physalis peruviana resulted in the isolation of 11 new withanolides, including perulactones I-L (1-4), 17-deoxy-23β-hydroxywithanolide E (5), 23β-hydroxywithanolide E (6), 4-deoxyphyperunolide A (7), 7β-hydroxywithanolide F (8), 7β-hydroxy-17-epi-withanolide K (9), 24,25-dihydro-23β,28-dihydroxywithanolide G (10), and 24,25-dihydrowithanolide E (11), together with 14 known withanolides (12-25). The structures of 1-11 were elucidated by the analysis of their spectroscopic data, and 12-25 were identified by comparison of their spectroscopic data with those reported. All withanolides were evaluated for their cytotoxic activity against a panel of tumor cell lines including LNCaP (androgen-sensitive human prostate adenocarcinoma), 22Rv1 (androgen-resistant human prostate adenocarcinoma), ACHN (human renal adenocarcinoma), M14 (human melanoma), SK-MEL-28 (human melanoma), and normal human foreskin fibroblast cells. Of these, the 17β-hydroxywithanolides (17-BHWs) 6, 8, 9, 11-13, 15, and 19-22 showed selective cytotoxic activity against the two prostate cancer cell lines LNCaP and 22Rv1, whereas 13 and 20 exhibited selective toxicity for the ACHN renal carcinoma cell line. These cytotoxicity data provide additional structure-activity relationship information for the 17-BHWs.

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References

Sang-Ngern M, Youn U, Park E, Kondratyuk T, Simmons C, Wall M . Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity. Bioorg Med Chem Lett. 2016; 26(12):2755-2759. DOI: 10.1016/j.bmcl.2016.04.077. View

Xu Y, Bunting D, Liu M, Bandaranayake H, Gunatilaka A . 17β-Hydroxy-18-acetoxywithanolides from Aeroponically Grown Physalis crassifolia and Their Potent and Selective Cytotoxicity for Prostate Cancer Cells. J Nat Prod. 2016; 79(4):821-30. DOI: 10.1021/acs.jnatprod.5b00911. View

Chiu C, Haung J, Chang F, Huang K, Huang H, Huang H . Golden berry-derived 4β-hydroxywithanolide E for selectively killing oral cancer cells by generating ROS, DNA damage, and apoptotic pathways. PLoS One. 2013; 8(5):e64739. PMC: 3660349. DOI: 10.1371/journal.pone.0064739. View

Park E, Sang-Ngern M, Chang L, Pezzuto J . Induction of cell cycle arrest and apoptosis with downregulation of Hsp90 client proteins and histone modification by 4β-hydroxywithanolide E isolated from Physalis peruviana. Mol Nutr Food Res. 2016; 60(6):1482-500. DOI: 10.1002/mnfr.201500977. View

Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90. DOI: 10.3322/caac.20107. View

Zegarra-Moro O, Schmidt L, Huang H, Tindall D . Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells. Cancer Res. 2002; 62(4):1008-13. View

Schrijvers D, Van Erps P, Cortvriend J . Castration-refractory prostate cancer: New drugs in the pipeline. Adv Ther. 2010; 27(5):285-96. DOI: 10.1007/s12325-010-0038-1. View

Vitali G, Conte L, Nicoletti M . Withanolide composition and in vitro culture of Italian Withania somnifera. Planta Med. 1996; 62(3):287-8. DOI: 10.1055/s-2006-957884. View

Yen C, Chiu C, Chang F, Chen J, Hwang C, Hseu Y . 4beta-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest. BMC Cancer. 2010; 10:46. PMC: 2830937. DOI: 10.1186/1471-2407-10-46. View

10.

Brooks A, Jacobsen K, Li W, Shanker A, Sayers T . Bortezomib sensitizes human renal cell carcinomas to TRAIL apoptosis through increased activation of caspase-8 in the death-inducing signaling complex. Mol Cancer Res. 2010; 8(5):729-38. PMC: 2873082. DOI: 10.1158/1541-7786.MCR-10-0022. View

11.

Asangani I, Dommeti V, Wang X, Malik R, Cieslik M, Yang R . Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014; 510(7504):278-82. PMC: 4075966. DOI: 10.1038/nature13229. View

12.

Mcdermott D, Atkins M . Interleukin-2 therapy of metastatic renal cell carcinoma--predictors of response. Semin Oncol. 2006; 33(5):583-7. DOI: 10.1053/j.seminoncol.2006.06.004. View

13.

Fang S, Liu J, Li B . Ten new withanolides from Physalis peruviana. Steroids. 2011; 77(1-2):36-44. DOI: 10.1016/j.steroids.2011.09.011. View

14.

Sanford M . Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. Drugs. 2013; 73(15):1723-32. DOI: 10.1007/s40265-013-0129-9. View

15.

Damu A, Kuo P, Su C, Kuo T, Chen T, Bastow K . Isolation, structures, and structure - cytotoxic activity relationships of withanolides and physalins from Physalis angulata. J Nat Prod. 2007; 70(7):1146-52. DOI: 10.1021/np0701374. View

16.

Xu Y, Gao S, Bunting D, Gunatilaka A . Unusual withanolides from aeroponically grown Withania somnifera. Phytochemistry. 2011; 72(6):518-22. DOI: 10.1016/j.phytochem.2010.12.020. View

17.

Ozawa M, Morita M, Hirai G, Tamura S, Kawai M, Tsuchiya A . Contribution of Cage-Shaped Structure of Physalins to Their Mode of Action in Inhibition of NF-κB Activation. ACS Med Chem Lett. 2014; 4(8):730-5. PMC: 4027496. DOI: 10.1021/ml400144e. View

18.

Wang H, Tsai Y, Wu Y, Chang F, Liu M, Chen W . Withanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90. PLoS One. 2012; 7(5):e37764. PMC: 3365124. DOI: 10.1371/journal.pone.0037764. View

19.

You B, Wu Y, Lee C, Lee H . Non-homologous end joining pathway is the major route of protection against 4β-hydroxywithanolide E-induced DNA damage in MCF-7 cells. Food Chem Toxicol. 2013; 65:205-12. DOI: 10.1016/j.fct.2013.12.026. View

20.

Fang S, Liu J, Li B . A novel 1,10-seco withanolide from Physalis peruviana. J Asian Nat Prod Res. 2010; 12(7):618-22. DOI: 10.1080/10286020.2010.482523. View