+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model

A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model

Cancer Research 65(23): 11203-11213

In prostate cancer, a fine balance between cell proliferation and apoptotic death is lost, resulting in increased cellular mass and tumor progression. One approach to redress this imbalance and control this malignancy is its preventive intervention through the use of dietary natural agents. Here, we investigated the growth-inhibitory effect and associated mechanisms of Lupeol, a triterpene present in fruits and vegetables, in androgen-sensitive human prostate cancer cells. Lupeol treatment resulted in significant inhibition of cell viability in a dose-dependent manner and caused apoptotic death of prostate cancer cells. Lupeol was found to induce the cleavage of poly(ADP-ribose) polymerase protein and degradation of acinus protein with a significant increase in the expression of FADD protein. Among all death receptor targets examined, Lupeol specifically caused a significant increase in the expression of Fas receptor. The small interfering RNA-mediated silencing of the Fas gene and inhibition of caspase-6, caspase-8, and caspase-9 by their specific inhibitors confirmed that Lupeol specifically activates the Fas receptor-mediated apoptotic pathway in androgen-sensitive prostate cancer cells. The treatment of cells with a combination of anti-Fas monoclonal antibody and Lupeol resulted in higher cell death compared with the additive effect of the two compounds alone, suggesting a synergistic effect. Lupeol treatment resulted in a significant inhibition in growth of tumors with concomitant reduction in prostate-specific antigen secretion in athymic nude mice implanted with CWR22Rnu1 cells. Because early clinical prostate cancer growth is an androgen-dependent response, the results of the present study suggest that Lupeol may have a potential to be an effective agent against prostate cancer.

(PDF emailed within 0-6 h: $19.90)

Accession: 011697870

Download citation: RISBibTeXText

PMID: 16322271

DOI: 10.1158/0008-5472.CAN-05-1965

Related references

Inositol hexaphosphate inhibits growth and induces G1 arrest and apoptotic death of androgen-dependent human prostate carcinoma LNCaP cells. Neoplasia 6(5): 646-659, 2004

Penta-1,2,3,4,6-O-galloyl-beta-D-glucose induces p53 and inhibits STAT3 in prostate cancer cells in vitro and suppresses prostate xenograft tumor growth in vivo. Molecular Cancer Therapeutics 7(9): 2681-2691, 2008

Lupeol, a fruit and vegetable based triterpene, induces apoptotic death of human pancreatic adenocarcinoma cells via inhibition of Ras signaling pathway. Carcinogenesis 26(11): 1956-1964, 2005

TLR3 engagement induces IRF-3-dependent apoptosis in androgen-sensitive prostate cancer cells and inhibits tumour growth in vivo. Journal of Cellular and Molecular Medicine 19(2): 327-339, 2015

Androgen receptor down regulation by small interference RNA induces cell growth inhibition in androgen sensitive as well as in androgen independent prostate cancer cells. Journal of Steroid Biochemistry and Molecular Biology 96(3-4): 251-258, 2005

Chlorella sorokiniana induces mitochondrial-mediated apoptosis in human non-small cell lung cancer cells and inhibits xenograft tumor growth in vivo. Bmc Complementary and Alternative Medicine 17(1): 88-88, 2017

Resiniferatoxin induces death of bladder cancer cells associated with mitochondrial dysfunction and reduces tumor growth in a xenograft mouse model. Chemico-Biological Interactions 224: 128-135, 2014

ERRgamma suppresses cell proliferation and tumor growth of androgen-sensitive and androgen-insensitive prostate cancer cells and its implication as a therapeutic target for prostate cancer. Cancer Research 67(10): 4904-4914, 2007

Evaluation of androgen-induced effects on the uptake of [18F]FDG, [11C]choline and [11C]acetate in an androgen-sensitive and androgen-independent prostate cancer xenograft model. Ejnmmi Research 3(1): 31-31, 2013

Silibinin suppresses growth and induces apoptotic death of human colorectal carcinoma LoVo cells in culture and tumor xenograft. Molecular Cancer Therapeutics 8(8): 2366-2374, 2010

The fractionated Toona sinensis leaf extract induces apoptosis of human ovarian cancer cells and inhibits tumor growth in a murine xenograft model. Gynecologic Oncology 102(2): 309-314, 2006

Development of an androgen receptor-null model for identifying the initiation site for androgen stimulation of proliferation and suppression of programmed (apoptotic) death of PC-82 human prostate cancer cells. Cancer Research 58(15): 3299-3306, 1998

Anthocyanin induces apoptosis of DU-145 cells in vitro and inhibits xenograft growth of prostate cancer. Yonsei Medical Journal 56(1): 16-23, 2015

Selenite treatment inhibits LAPC-4 tumor growth and prostate-specific antigen secretion in a xenograft model of human prostate cancer. International Journal of Radiation Oncology, Biology, Physics 72(3): 935-940, 2008

ProstaCaid inhibits tumor growth in a xenograft model of human prostate cancer. International Journal of Oncology 40(5): 1339-1344, 2012