Cellular Changes in Boric Acid-treated DU-145 Prostate Cancer Cells

Overview

Journal Br J Cancer

Specialty Oncology

Date 2006 Feb 24

PMID 16495920

Citations 22

Authors

W T Barranco

C D Eckhert

Affiliations

Soon will be listed here.

Abstract

Epidemiological, animal, and cell culture studies have identified boron as a chemopreventative agent in prostate cancer. The present objective was to identify boron-induced changes in the DU-145 human prostate cancer cell line. We show that prolonged exposure to pharmacologically-relevant levels of boric acid, the naturally occurring form of boron circulating in human plasma, induces the following morphological changes in cells: increases in granularity and intracellular vesicle content, enhanced cell spreading and decreased cell volume. Documented increases in beta-galactosidase activity suggest that boric acid induces conversion to a senescent-like cellular phenotype. Boric acid also causes a dose-dependent reduction in cyclins A-E, as well as MAPK proteins, suggesting their contribution to proliferative inhibition. Furthermore, treated cells display reduced adhesion, migration and invasion potential, along with F-actin changes indicative of reduced metastatic potential. Finally, the observation of media acidosis in treated cells correlated with an accumulation of lysosome-associated membrane protein type 2 (LAMP-2)-negative acidic compartments. The challenge of future studies will be to identify the underlying mechanism responsible for the observed cellular responses to this natural blood constituent.

Citing Articles

In vitro cytotoxic and apoptotic effects of boric acid on endometrial adenocarcinoma cell lines (HEC-1B and Ischikawa).

Cil N, Onder E, Damar A, Tabatabaei S, Cabus U, Mete G Med Oncol. 2025; 42(3):79.

PMID: 39971813 PMC: 11839787. DOI: 10.1007/s12032-025-02625-4.

Boric acid and zinc borate doped graphene hydrogels designed for burn treatment: In vitro viability-biocompatibility tests and microbiological analysis.

Bayir Y, Erkayman B, Albayrak A, Palabiyik-Yucelik S, Can S, Hanci H J Biomater Appl. 2024; 39(6):592-606.

PMID: 39302915 PMC: 11707965. DOI: 10.1177/08853282241268673.

Protective Effects of Boric Acid Taken in Different Ways on Experimental Ovarian İschemia and Reperfusion.

Karaman E, Onder G, Goktepe O, Karakas E, Cengiz Mat O, Bolat D Biol Trace Elem Res. 2023; 202(6):2730-2743.

PMID: 37743417 DOI: 10.1007/s12011-023-03871-1.

Redox Mechanisms Underlying the Cytostatic Effects of Boric Acid on Cancer Cells-An Issue Still Open.

Paties Montagner G, Dominici S, Piaggi S, Pompella A, Corti A Antioxidants (Basel). 2023; 12(6).

PMID: 37372032 PMC: 10294879. DOI: 10.3390/antiox12061302.

Therapeutic Efficacy of Boric Acid Treatment on Brain Tissue and Cognitive Functions in Rats with Experimental Alzheimer's Disease.

Ozdemir C, Arslan M, Kucuk A, Yigman Z, Dursun A Drug Des Devel Ther. 2023; 17:1453-1462.

PMID: 37220543 PMC: 10200114. DOI: 10.2147/DDDT.S405963.

References

Gallardo-Williams M, Chapin R, King P, Moser G, Goldsworthy T, Morrison J . Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicol Pathol. 2004; 32(1):73-8. DOI: 10.1080/01926230490260899. View

Giehl K . Oncogenic Ras in tumour progression and metastasis. Biol Chem. 2005; 386(3):193-205. DOI: 10.1515/BC.2005.025. View

Glunde K, Guggino S, Solaiyappan M, Pathak A, Ichikawa Y, Bhujwalla Z . Extracellular acidification alters lysosomal trafficking in human breast cancer cells. Neoplasia. 2004; 5(6):533-45. PMC: 1502575. DOI: 10.1016/s1476-5586(03)80037-4. View

Maddison L, Huss W, Barrios R, Greenberg N . Differential expression of cell cycle regulatory molecules and evidence for a "cyclin switch" during progression of prostate cancer. Prostate. 2004; 58(4):335-44. DOI: 10.1002/pros.10341. View

Bennett A, Rowe R, Soch N, Eckhert C . Boron stimulates yeast (Saccharomyces cerevisiae) growth. J Nutr. 1999; 129(12):2236-8. DOI: 10.1093/jn/129.12.2236. View

Kurz D, Decary S, Hong Y, Erusalimsky J . Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci. 2000; 113 ( Pt 20):3613-22. DOI: 10.1242/jcs.113.20.3613. View

Lang F, Ritter M, Gamper N, Huber S, Fillon S, Tanneur V . Cell volume in the regulation of cell proliferation and apoptotic cell death. Cell Physiol Biochem. 2000; 10(5-6):417-28. DOI: 10.1159/000016367. View

Chen X, Schauder S, Potier N, Van Dorsselaer A, Pelczer I, Bassler B . Structural identification of a bacterial quorum-sensing signal containing boron. Nature. 2002; 415(6871):545-9. DOI: 10.1038/415545a. View

Coates P . Markers of senescence?. J Pathol. 2002; 196(4):371-3. DOI: 10.1002/path.1073. View

10.

Takano J, Noguchi K, Yasumori M, Kobayashi M, Gajdos Z, Miwa K . Arabidopsis boron transporter for xylem loading. Nature. 2002; 420(6913):337-40. DOI: 10.1038/nature01139. View

11.

Gallardo-Williams M, Maronpot R, Wine R, Brunssen S, Chapin R . Inhibition of the enzymatic activity of prostate-specific antigen by boric acid and 3-nitrophenyl boronic acid. Prostate. 2002; 54(1):44-9. DOI: 10.1002/pros.10166. View

12.

Mukhopadhyay A, Banerjee S, Stafford L, Xia C, Liu M, Aggarwal B . Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation. Oncogene. 2002; 21(57):8852-61. DOI: 10.1038/sj.onc.1206048. View

13.

Lecane P, Kiviharju T, Sellers R, Peehl D . Leptomycin B stabilizes and activates p53 in primary prostatic epithelial cells and induces apoptosis in the LNCaP cell line. Prostate. 2003; 54(4):258-67. DOI: 10.1002/pros.10197. View

14.

Eskelinen E, Tanaka Y, Saftig P . At the acidic edge: emerging functions for lysosomal membrane proteins. Trends Cell Biol. 2003; 13(3):137-45. DOI: 10.1016/s0962-8924(03)00005-9. View

15.

Kim D, Marbois B, Faull K, Eckhert C . Esterification of borate with NAD+ and NADH as studied by electrospray ionization mass spectrometry and 11B NMR spectroscopy. J Mass Spectrom. 2003; 38(6):632-40. DOI: 10.1002/jms.476. View

16.

Cui Y, Winton M, Zhang Z, Rainey C, Marshall J, De Kernion J . Dietary boron intake and prostate cancer risk. Oncol Rep. 2004; 11(4):887-92. View

17.

Tsao A, Kim E, Hong W . Chemoprevention of cancer. CA Cancer J Clin. 2004; 54(3):150-80. DOI: 10.3322/canjclin.54.3.150. View

18.

Lambrechts A, Van Troys M, Ampe C . The actin cytoskeleton in normal and pathological cell motility. Int J Biochem Cell Biol. 2004; 36(10):1890-909. DOI: 10.1016/j.biocel.2004.01.024. View

19.

Semmelhack M, Campagna S, Hwa C, Federle M, Bassler B . Boron binding with the quorum sensing signal AI-2 and analogues. Org Lett. 2004; 6(15):2635-7. DOI: 10.1021/ol048976u. View

20.

Kim D, Faull K, Norris A, Eckhert C . Borate-nucleotide complex formation depends on charge and phosphorylation state. J Mass Spectrom. 2004; 39(7):743-51. DOI: 10.1002/jms.645. View