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Activation of polyamine catabolic enzymes involved in diverse responses against epibrassinolide-induced apoptosis in LNCaP and DU145 prostate cancer cell lines.
Amino Acids. 2014 Mar; 46(3):553-64.AA

Abstract

Epibrassinolide (EBR) is a biologically active compound of the brassinosteroids, steroid-derived plant growth regulator family. Generally, brassinosteroids are known for their cell expansion and cell division-promoting roles. Recently, EBR was shown as a potential apoptotic inducer in various cancer cells without affecting the non-tumor cell growth. Androgen signaling controls cell proliferation through the interaction with the androgen receptor (AR) in the prostate gland. Initially, the development of prostate cancer is driven by androgens. However, in later stages, a progress to the androgen-independent stage is observed, resulting in metastatic prostate cancer. The androgen-responsive or -irresponsive cells are responsible for tumor heterogeneity, which is an obstacle to effective anti-cancer therapy. Polyamines are amine-derived organic compounds, known for their role in abnormal cell proliferation as well as during malignant transformation. Polyamine catabolism-targeting agents are being investigated against human cancers. Many chemotherapeutic agents including polyamine analogs have been demonstrated to induce polyamine catabolism that depletes polyamine levels and causes apoptosis in tumor models. In our study, we aimed to investigate the mechanism of apoptotic cell death induced by EBR, related with polyamine biosynthetic and catabolic pathways in LNCaP (AR+), DU145 (AR-) prostate cancer cell lines and PNT1a normal prostate epithelial cell line. Induction of apoptotic cell death was observed in prostate cancer cell lines after EBR treatment. In addition, EBR induced the decrease of intracellular polyamine levels, accompanied by a significant ornithine decarboxylase (ODC) down-regulation in each prostate cancer cell and also modulated ODC antizyme and antizyme inhibitor expression levels only in LNCaP cells. Catabolic enzymes SSAT and PAO expression levels were up-regulated in both cell lines; however, the specific SSAT and PAO siRNA treatments prevented the EBR-induced apoptosis only in LNCaP (AR+) cells. In a similar way, MDL 72,527, the specific PAO and SMO inhibitor, co-treatment with EBR during 24 h, reduced the formation of cleaved fragments of PARP in LNCaP (AR+) cells.

Authors+Show Affiliations

Department of Molecular Biology and Genetics, Istanbul Kultur University, Atakoy Campus, Bakirkoy, 34156, Istanbul, Turkey.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23963538

Citation

Obakan, Pinar, et al. "Activation of Polyamine Catabolic Enzymes Involved in Diverse Responses Against Epibrassinolide-induced Apoptosis in LNCaP and DU145 Prostate Cancer Cell Lines." Amino Acids, vol. 46, no. 3, 2014, pp. 553-64.
Obakan P, Arisan ED, Calcabrini A, et al. Activation of polyamine catabolic enzymes involved in diverse responses against epibrassinolide-induced apoptosis in LNCaP and DU145 prostate cancer cell lines. Amino Acids. 2014;46(3):553-64.
Obakan, P., Arisan, E. D., Calcabrini, A., Agostinelli, E., Bolkent, S., & Palavan-Unsal, N. (2014). Activation of polyamine catabolic enzymes involved in diverse responses against epibrassinolide-induced apoptosis in LNCaP and DU145 prostate cancer cell lines. Amino Acids, 46(3), 553-64. https://doi.org/10.1007/s00726-013-1574-1
Obakan P, et al. Activation of Polyamine Catabolic Enzymes Involved in Diverse Responses Against Epibrassinolide-induced Apoptosis in LNCaP and DU145 Prostate Cancer Cell Lines. Amino Acids. 2014;46(3):553-64. PubMed PMID: 23963538.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of polyamine catabolic enzymes involved in diverse responses against epibrassinolide-induced apoptosis in LNCaP and DU145 prostate cancer cell lines. AU - Obakan,Pinar, AU - Arisan,Elif Damla, AU - Calcabrini,Annarica, AU - Agostinelli,Enzo, AU - Bolkent,Sehnaz, AU - Palavan-Unsal,Narçin, Y1 - 2013/08/21/ PY - 2013/05/22/received PY - 2013/07/31/accepted PY - 2013/8/22/entrez PY - 2013/8/22/pubmed PY - 2015/2/11/medline SP - 553 EP - 64 JF - Amino acids JO - Amino Acids VL - 46 IS - 3 N2 - Epibrassinolide (EBR) is a biologically active compound of the brassinosteroids, steroid-derived plant growth regulator family. Generally, brassinosteroids are known for their cell expansion and cell division-promoting roles. Recently, EBR was shown as a potential apoptotic inducer in various cancer cells without affecting the non-tumor cell growth. Androgen signaling controls cell proliferation through the interaction with the androgen receptor (AR) in the prostate gland. Initially, the development of prostate cancer is driven by androgens. However, in later stages, a progress to the androgen-independent stage is observed, resulting in metastatic prostate cancer. The androgen-responsive or -irresponsive cells are responsible for tumor heterogeneity, which is an obstacle to effective anti-cancer therapy. Polyamines are amine-derived organic compounds, known for their role in abnormal cell proliferation as well as during malignant transformation. Polyamine catabolism-targeting agents are being investigated against human cancers. Many chemotherapeutic agents including polyamine analogs have been demonstrated to induce polyamine catabolism that depletes polyamine levels and causes apoptosis in tumor models. In our study, we aimed to investigate the mechanism of apoptotic cell death induced by EBR, related with polyamine biosynthetic and catabolic pathways in LNCaP (AR+), DU145 (AR-) prostate cancer cell lines and PNT1a normal prostate epithelial cell line. Induction of apoptotic cell death was observed in prostate cancer cell lines after EBR treatment. In addition, EBR induced the decrease of intracellular polyamine levels, accompanied by a significant ornithine decarboxylase (ODC) down-regulation in each prostate cancer cell and also modulated ODC antizyme and antizyme inhibitor expression levels only in LNCaP cells. Catabolic enzymes SSAT and PAO expression levels were up-regulated in both cell lines; however, the specific SSAT and PAO siRNA treatments prevented the EBR-induced apoptosis only in LNCaP (AR+) cells. In a similar way, MDL 72,527, the specific PAO and SMO inhibitor, co-treatment with EBR during 24 h, reduced the formation of cleaved fragments of PARP in LNCaP (AR+) cells. SN - 1438-2199 UR - https://www.unboundmedicine.com/medline/citation/23963538/Activation_of_polyamine_catabolic_enzymes_involved_in_diverse_responses_against_epibrassinolide_induced_apoptosis_in_LNCaP_and_DU145_prostate_cancer_cell_lines_ L2 - https://dx.doi.org/10.1007/s00726-013-1574-1 DB - PRIME DP - Unbound Medicine ER -