Lupeol inhibits proliferation of human prostate cancer cells by targeting β-catenin signaling

Mohammad Saleem, Imtiyaz Murtaza, Rohinton S. Tarapore, Yewseok Suh, Vaqar Mustafa Adhami, Jeremy James Johnson, Imtiaz Ahmad Siddiqui, Naghma Khan, Mohammad Asim, Bilal Hafeez, Mohammed Talha Shekhani, Benyi Li, Hasan Mukhtar

Research output: Contribution to journalArticle

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Abstract

Lupeol, a dietary triterpene, was shown to decrease serum prostate-specific antigen levels and inhibit the tumorigenicity of prostate cancer (CaP) cells in vivo. Here, we show that Lupeol inhibits the proliferative potential of CaP cells and delineated its mechanism of action. Employing a focused microarray of human CaP-associated genes, we found that Lupeol significantly modulates the expression level of genes such as ERBB2, tissue inhibitor of metalloproteinases-3, cyclin D1 and matrix metalloproteinase (MMP)-2 that are known to be associated with proliferation and survival. A common feature of these genes is that all of them are known to either regulate or act as downstream target of β-catenin signaling that is highly aberrant in CaP patients. Lupeol treatment significantly (1) reduced levels of β-catenin in the cytoplasmic and nuclear fractions, (2) modulated expression levels of glycogen synthase kinase 3 beta (GSK3β)-axin complex (regulator of β-catenin stability), (3) decreased the expression level and enzymatic activity of MMP-2 (downstream target of β-catenin), (4) reduced the transcriptional activation of T Cell Factor (TCF) responsive element (marker for β-catenin signaling) in pTK-TCF-Luc-transfected cells and (5) decreased the transcriptional activation of MMP-2 gene in pGL2-MMP-2-Luc-transfected cells. Effects of Lupeol treatment on β-catenin degradation were significantly reduced in CaP cells where axin is knocked down through small interfering RNA transfection and GSK3β activity is blocked. Collectively, these data suggest the multitarget efficacy of Lupeol on β-catenin-signaling network thus resulting in the inhibition CaP cell proliferation. We suggest that Lupeol could be developed as an agent for chemoprevention as well as chemotherapy of human CaP.

Original languageEnglish (US)
Pages (from-to)808-817
Number of pages10
JournalCarcinogenesis
Volume30
Issue number5
DOIs
StatePublished - May 13 2009
Externally publishedYes

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Catenins
Prostatic Neoplasms
Matrix Metalloproteinase 2
TCF Transcription Factors
Transcriptional Activation
Tissue Inhibitor of Metalloproteinase-3
Genes
Triterpenes
Cyclin D1
Chemoprevention
Prostate-Specific Antigen
lupeol
Small Interfering RNA
Transfection
Cell Proliferation
Gene Expression
Drug Therapy
Survival
Therapeutics
Serum

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Saleem, M., Murtaza, I., Tarapore, R. S., Suh, Y., Adhami, V. M., Johnson, J. J., ... Mukhtar, H. (2009). Lupeol inhibits proliferation of human prostate cancer cells by targeting β-catenin signaling. Carcinogenesis, 30(5), 808-817. https://doi.org/10.1093/carcin/bgp044

Lupeol inhibits proliferation of human prostate cancer cells by targeting β-catenin signaling. / Saleem, Mohammad; Murtaza, Imtiyaz; Tarapore, Rohinton S.; Suh, Yewseok; Adhami, Vaqar Mustafa; Johnson, Jeremy James; Siddiqui, Imtiaz Ahmad; Khan, Naghma; Asim, Mohammad; Hafeez, Bilal; Shekhani, Mohammed Talha; Li, Benyi; Mukhtar, Hasan.

In: Carcinogenesis, Vol. 30, No. 5, 13.05.2009, p. 808-817.

Research output: Contribution to journalArticle

Saleem, M, Murtaza, I, Tarapore, RS, Suh, Y, Adhami, VM, Johnson, JJ, Siddiqui, IA, Khan, N, Asim, M, Hafeez, B, Shekhani, MT, Li, B & Mukhtar, H 2009, 'Lupeol inhibits proliferation of human prostate cancer cells by targeting β-catenin signaling', Carcinogenesis, vol. 30, no. 5, pp. 808-817. https://doi.org/10.1093/carcin/bgp044
Saleem M, Murtaza I, Tarapore RS, Suh Y, Adhami VM, Johnson JJ et al. Lupeol inhibits proliferation of human prostate cancer cells by targeting β-catenin signaling. Carcinogenesis. 2009 May 13;30(5):808-817. https://doi.org/10.1093/carcin/bgp044
Saleem, Mohammad ; Murtaza, Imtiyaz ; Tarapore, Rohinton S. ; Suh, Yewseok ; Adhami, Vaqar Mustafa ; Johnson, Jeremy James ; Siddiqui, Imtiaz Ahmad ; Khan, Naghma ; Asim, Mohammad ; Hafeez, Bilal ; Shekhani, Mohammed Talha ; Li, Benyi ; Mukhtar, Hasan. / Lupeol inhibits proliferation of human prostate cancer cells by targeting β-catenin signaling. In: Carcinogenesis. 2009 ; Vol. 30, No. 5. pp. 808-817.
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