Sulindac derivatives inhibit growth and induce apoptosis in human prostate cancer cell lines

Lim, Jin T. E.; Piazza, Gary A.; Han, Edward K.; Delohery, Thomas; Han, Li; Finn, Tyler S.; Buttyan, Ralph; Yamamoto, Hideya; Sperl, Gerhard; Brendel, Klaus; Gross, Paul R.; Pamukcu, Rifat; Weinstein, I. Bernard

doi:10.1016/s0006-2952(99)00200-2

Cited by 178 publications

(97 citation statements)

References 30 publications

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“…2, higher concentrations of sulindac sulfide were required to inhibit the growth of HCT-116 on soft agar than were required to induce apoptosis. This finding is in agreement with previous reports in the literature and may be related to the presence of 10% serum in the incubation mixture that would bind up the sulindac sulfide thus requiring a higher concentration to elicit a response (38) similar to that seen here by FACS analysis (Fig. 1).…”

Section: Sulindac Sulfide Induces Apoptosis and Inhibits Clonogenicsupporting

confidence: 93%

Gene Modulation by the Cyclooxygenase Inhibitor, Sulindac Sulfide, in Human Colorectal Carcinoma Cells

Bottone

Martinez

Collins

et al. 2003

Journal of Biological Chemistry

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The mechanisms underlying the anti-tumorigenic properties of cyclooxygenase inhibitors are not well understood. One novel hypothesis is alterations in gene expression. To test this hypothesis sulindac sulfide, which is used to treat familial adenomatous polyposis, was selected to detect gene modulation in human colorectal cells at physiological concentrations with microarray analysis. At micromolar concentrations, sulindac sulfide stimulated apoptosis and inhibited the growth of colorectal cancer cells on soft agar. Sulindac sulfide (10 M) altered the expression of 65 genes in SW-480 colorectal cancer cells, which express cyclooxygenase-1 but little cyclooxygenase-2. A more detailed study of 11 genes revealed that their expression was altered in a time-and dose-dependent manner as measured by real-time RT-PCR. Northern analysis confirmed the expression of 9 of these genes, and Western analysis supported the conclusion that sulindac sulfide altered the expression of these proteins. Cyclooxygenase-deficient HCT-116 cells were more responsive to sulindac sulfide-induced gene expression than SW-480 cells. However, this response was diminished in HCT-116 cells overexpressing cyclooxygenase-1 compared with normal HCT-116 cells suggesting the presence of cyclooxygenase attenuates this response. However, prostaglandin E 2 , the main product of cyclooxygenase, only suppressed the sulindac sulfide-induced expression of two genes, with little known biological function while it modulated the expression of two more. The most likely explanation for this finding is the metabolism of sulindac sulfide to inactive metabolites by the peroxidase activity of cyclooxygenase. In conclusion, this is the first report showing sulindac sulfide, independent of cyclooxygenase, altered the expression of several genes possibly linked to its anti-tumorigenic and pro-apoptotic activity.

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Section: Sulindac Sulfide Induces Apoptosis and Inhibits Clonogenicsupporting

confidence: 93%

Gene Modulation by the Cyclooxygenase Inhibitor, Sulindac Sulfide, in Human Colorectal Carcinoma Cells

Bottone

Martinez

Collins

et al. 2003

Journal of Biological Chemistry

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“…Nontransformed WI-38 lung fibroblasts were grown in Eagle's MEM supplemented with 10% (vol/vol) FBS and antibiotics. Not transformed (BPH1) and transformed (PC3) prostate cell lines were maintained in RPMI 1640 medium supplemented with 10% (vol/vol) FBS and antibiotics (18). Three subcloned cell lines from human ovarian cancer primary cells were maintained in KO-DMEM media, 15% (vol/vol) FBS, 16.5% (vol/vol) Medium 199, 3.5 mM L-glutamine, and antibiotics.…”

Section: Methodsmentioning

confidence: 99%

Alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation

Rotem

Janzer

Izar

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

110

100

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Colony formation in soft agar is the gold-standard assay for cellular transformation in vitro, but it is unsuited for high-throughput screening. Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-agar assay. Using GILA, we describe high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. Such molecules are unlikely to be found through conventional drug screening, and they include kinase inhibitors and drugs for noncancer diseases. In addition to known oncogenes, the genetic screen identifies genes that contribute to cellular transformation. Lastly, we demonstrate the ability of Food and Drug Administration-approved noncancer drugs to selectively kill ovarian cancer cells derived from patients with chemotherapy-resistant disease, suggesting this approach may provide useful information for personalized cancer treatment.

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“…It might be suggested that COX-2 inhibitors, through inhibition of the proinflammatroy cytokines, inhibit the procession of precancerous lesions and the angiogenesis of tumors. In fact, studies in experimental models have shown that COX-2 inhibitors suppress the growth and angiogenesis of prostate cancer (7,14,37,43,44). In addition, several studies have already recognized that nonsteroidal anti-inflammatory drugs have a dramatic antitumor effect in prostate cancer both in vivo (45) and in vitro (10).…”

Section: Imaging Diagnosis Prognosismentioning

confidence: 99%

Cyclooxygenase-2 Expression Correlates with Local Chronic Inflammation and Tumor Neovascularization in Human Prostate Cancer

Wang

Bergh

Damber

2005

Clinical Cancer Research

140

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Purpose: Chronic inflammation is linked to the development of cancer in several organs, including the prostate. Up-regulated cyclooxygenase-2 (COX-2) may play a role in influencing cell proliferation, differentiation, apoptosis, or angiogenesis.This study aimed to derive data from human prostate cancer to investigate whether chronic inflammation and angiogenesis were correlated with the expression of COX-2. Experimental Design: In this study, we did double-immunohistochemical analysis of a set of 43 human prostate cancer for COX-2 expression and the correlation with T-lymphocyte and macrophage densities and CD31-marked microvessel density (MVD) in situ. Results: COX-2 positive staining was detected in 40/43 cancer samples with the very heterogeneous expression. Elevated COX-2 expression was associated with high Gleason score (P = 0.002). Foci of chronic inflammation were found in all 43 samples. COX-2^positive areas were noted with high T-lymphocyte and macrophage densities than COX-2^negative tumor areas (P < 0.0001and P = 0.001, respectively). MVD were also found higher in COX-2^positive areas than in COX-2^negative tumor areas (P = 0.001).Conclusions: This study shows a novel relationship between COX-2 expression and the local chronic inflammation within prostate cancer and the increased angiogenesis. It is likely that the proinflmmatory cytokines, released by T-lymphocytes and macrophages, up-regulate COX-2 in adjacent tumor cells and stimulate the angiogenesis in stromal tissues.These findings suggest that COX-2 may be an effective therapeutic target in prostate cancer treatment.

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Sulindac derivatives inhibit growth and induce apoptosis in human prostate cancer cell lines

Cited by 178 publications

References 30 publications

Gene Modulation by the Cyclooxygenase Inhibitor, Sulindac Sulfide, in Human Colorectal Carcinoma Cells

Gene Modulation by the Cyclooxygenase Inhibitor, Sulindac Sulfide, in Human Colorectal Carcinoma Cells

Alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation

Cyclooxygenase-2 Expression Correlates with Local Chronic Inflammation and Tumor Neovascularization in Human Prostate Cancer

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