Atorvastatin and Celecoxib Inhibit Prostate PC-3 Tumors in Immunodeficient Mice

Zheng, Xi; Cui, Xiaojie; Avila, Gina E.; Huang, Mou‐Tuan; Liu, Yue; Patel, Jagruti A.; Kong, Ah Ng Tony; Paulino, Raphael; Shih, Weichung Joe; Lin, Yong; Rabson, Arnold B.; Reddy, Bandaru S.; Conney, Allan H.

doi:10.1158/1078-0432.ccr-07-0242

Cited by 69 publications

(65 citation statements)

References 35 publications

(33 reference statements)

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“…In a xenograft tumor model, daily introperitoneal injections of high dose of atorvastatin (10 lg/g body weight) or celecoxib (10 lg/g body weight) showed little or no effect on the formation of androgen-independent prostate tumors that occurred after subcutaneous injection of PC-3 cells in male severe combined immunodeficient mice. 57 In contrast, the administration with a low-dose combination of atorvastatin (5 lg/g body weight) plus celecoxib (5 lg/g body weight) significantly delayed the formation of the tumors, and some of mice the remained tumor-free throughout the whole experiment period. The low-dose combination of the 2 agents also had a stronger inhibitory effect on the tumor burden (53.3% reduction in the tumor size) than the higher dose of individual agent (20% reduction for atorvastatin, and 24.4% reduction for celecoxib).…”

Section: Cancer Chemoprevention By the Combinations Of Statins And Nsmentioning

confidence: 94%

Combination regimen with statins and NSAIDs: A promising strategy for cancer chemoprevention

Xiao

Yang

2008

Intl Journal of Cancer

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Statins and nonsteroidal antiinflammatory drugs (NSAIDs) are commonly prescribed for lowering cholesterol and antiinflammation, respectively. Recently, their potential roles as cancer chemopreventive agents have been subject to intensive studies. Human trials have not provided conclusive results on the protective effects of statins against different cancers, while more convincing results have been observed for cancer preventive effects of NSAIDs, especially on colorectal cancer. A promising strategy to enhance the cancer preventive efficacy of statins and NSAIDs is to use them in combination, which may produce synergy and lower the dose required for each agent. This strategy is of particular interest for potential use of low doses of statins and NSAIDs on a long-term basis for cancer chemoprevention; increased risks for gastrointestinal and cardiovascular side effects associated with the use of NSAIDs have been observed in colorectal cancer chemopreventive trials. This article reviews the evidence for the cancer preventive actions of statins and NSAIDs, as well as their possible synergistic action and the mechanisms involved. ' 2008 Wiley-Liss, Inc.Key words: statins; NSAIDs; cancer chemoprevention While the mortality from major chronic diseases, such as cardiovascular and cerebrovascular diseases, has decreased substantially during the past half century in the United States, the mortality from cancer has just begun to show a slight decrease. Cancer has become the number one killer of both men and women under age 85 years in the United States.1 A promising approach to controlling cancer is to prevent it before malignant events have occurred.2 Cancer chemoprevention refers to the use of natural or synthetic substances to inhibit, retard or reverse the carcinogenesis.3 A wealth of evidence from preclinical studies have convincingly demonstrated the cancer preventive efficacy of various agents in different animal models. However, the data from observational, case-control, cohort studies, and randomized trials in humans have overall demonstrated mixed results. Statins and nonsteroidal antiinflammatory drugs (NSAIDs) have been reported to be potential cancer chemopreventive agents. This review focuses on an attractive approach of chemoprevention using the combination of statins and NSAIDs. Statin and cancer chemopreventionStatins are small-molecule inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which are widely used as cholesterol-lowering drugs. Besides their use in the treatment of lipid disorders, statins have showed anticarcinogenic activities in many in vitro and in vivo preclinical studies, and attracted much attention in exploring their roles in cancer chemoprevention. Several observational human studies reported potential protective effects of statin use against overall risk of cancer, 4-6 whereas other studies did not 7,8 (Table I). In a case-control study in Quebec, Canada, statin use was found to be associated with a 28% reduction in the risk of developing cancer (RR 5 0.72, 95% ...

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Section: Cancer Chemoprevention By the Combinations Of Statins And Nsmentioning

confidence: 94%

Combination regimen with statins and NSAIDs: A promising strategy for cancer chemoprevention

Xiao

Yang

2008

Intl Journal of Cancer

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“…The number of viable cells following each treatment was determined using the trypan blue exclusion assay (31). In brief, 80 µl of cell suspension was mixed with 20 µl of 0.4% trypan blue solution and incubated for 2 min.…”

Section: Determination Of the Number Of Viable Cellsmentioning

confidence: 99%

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Wei

Cui

et al. 2012

Oncology Letters

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Abstract. Curcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Six cyclohexanone analogues of curcumin (A 1 -A 6 ) were investigated for their effects on growth and apoptosis in PC-3 human prostate cancer cells. The ability of these compounds to inhibit NF-κB activity in PC-3 cells was also determined. Five out of the six curcumin analogues (A 2 -A 6 ) had stronger inhibitory effects compared to curcumin on the growth of cultured PC-3 cells. Compounds A 2 -A 6 also had stronger stimulatory effects on apoptosis in PC-3 cells than curcumin, and these curcumin analogues more potently inhibited NF-κB activity than curcumin. The inhibitory effects of these compounds on NF-κB activity correlated with their effects on growth inhibition and apoptosis stimulation in PC-3 cells. The results of the present study provide a rationale for in vivo studies with A 2 -A 6 using suitable animal models of prostate cancer. IntroductionCurcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Curcumin lacks toxicity in humans (1), and extensive research over several decades has revealed that curcumin possesses anticancer, anti-inflammatory, antioxidant, antiviral and anti-bacterial activities (2,3). Curcumin suppressed cell proliferation or induced apoptosis in cultured prostate cancer cells and other types of cancer cells (4-10). Curcumin also inhibited prostate carcinogenesis (11). Studies from our laboratory and those of other authors have demonstrated enhanced anticancer activities of curcumin when combined with other anticancer agents (12-14). Findings of earlier studies showed that curcumin exerts a wide range of anticancer effects by modulating a diversity of signaling pathways, including nuclear factor-κB (NF-κB) and other pathways (15)(16)(17)(18)(19)(20). Curcumin has entered clinical trials for certain types of human cancer (21-23). However, the clinical efficacy of curcumin is limited, which is likely to be due to its low bioavailability (21-23). It was suggested that the β-diketone moiety of curcumin causes instability and poor metabolic properties (24-26). Enhanced stability was found in curcumin analogues by deleting the β-diketone moiety of the molecule (27). Recently, it was demonstrated that the cyclohexanone analogues of curcumin have enhanced stability in biological medium compared to curcumin (28). The cyclohexanone-containing curcumin analogue 2,6-bisp[(3-methoxy-4-hydroxyphenyl)methylene)]-cyclohexanone was found to be more potent than curcumin for inhibiting NF-κB in human breast cancer cells in vitro (29).In an earlier study, we synthesized a series of cyclohexanone curcumin analogues and determined their inhibitory effect on the activity of aldose reductase (30). In the present study, we investigated the effects of these curcumin analogues on the growth and apoptosis of human prostate cancer PC-3 cells. We also determined the inhibitory effect ...

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“…Similarly, in a recent study of fermented ginseng, another compound of Chinese medicine associated with anti-inflammatory effects, inhibition of NF-κB activity was detected (Yuan and Chung, 2010). Anti-tumor agents have also been shown to induce apoptosis by modulating NF-κB expression and activity (Pandey et al, 2007), Thus, strategies to inhibit NF-κB may provide a cancer therapy applicable to many types of carcinomas Zheng et al, 2007;Paule et al, 2007;Nonn et al, 2007). In this study, SN suppressed NF-κB activity and PGE2 production in a dose-dependent manner.…”

mentioning

confidence: 61%

Sinomenine induces apoptosis of prostate cancer cells by blocking activation of NF-kappa B

Fan¹,

Wang²,

Chen³

et al. 2011

Afr. J. Biotechnol.

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Sinomenine (SN) is an alkaloid that has previously been shown to have a role in such varied processes as inflammation, angiogenesis, arthritis and immunosuppression. Therefore, in this study, possible anti-tumor effects of SN on the human prostate cancer cell lines, PC-3 and DU-145, was investigated. After treatment with varying doses of SN, apoptosis was measured by flow cytometry. Prostaglandin E2 production was detected by ELISA, and expression levels of cyclooxygenase-2 and nuclear factorkappa B were evaluated by western blot. In both PC-3 and DU-145 cells, SN treatment induced apoptosis, inhibited in vitro production of prostaglandin E2, and decreased activation of cyclooxygenase-2 and nuclear factor-kappa B. Growth inhibition assays were also performed to determine whether cell viability was responsible for the decrease in the activation observed. In combination, these results suggest that SN can induce an anti-tumor response by suppressing the activation of cyclooxygenase-2 and nuclear factor-kappa B signaling pathways.

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Atorvastatin and Celecoxib Inhibit Prostate PC-3 Tumors in Immunodeficient Mice

Cited by 69 publications

References 35 publications

Combination regimen with statins and NSAIDs: A promising strategy for cancer chemoprevention

Combination regimen with statins and NSAIDs: A promising strategy for cancer chemoprevention

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Sinomenine induces apoptosis of prostate cancer cells by blocking activation of NF-kappa B

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