curcumin and Endometrial-Neoplasms

Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade in gynecological cancers showed objective responses in 13-17% of patients. This could be due to immunosuppressive effects exerted by gynecological tumors on the microenvironment and an altered tumor vasculature. In other malignancies, combining checkpoint blockade with radiation delivers benefit that is believed to be due to the abscopal effect. Addition of immune modulation agents has also shown to enhance immune checkpoint blockade efficacy. Therefore we designed a regimen consisting of PD-1 blockade combined with radiation, and different immune/environmental-targeting compounds: repurposed drugs, metronomic chemotherapy and a food supplement. We hypothesize that these will synergistically modulate the tumor microenvironment and induce and sustain an anti-tumor immune response, resulting in tumor regression.. PRIMMO is a multi-center, open-label, non-randomized, 3-cohort phase 2 study with safety run-in in patients with recurrent/refractory cervical carcinoma, endometrial carcinoma or uterine sarcoma. Treatment consists of daily intake of vitamin D, lansoprazole, aspirin, cyclophosphamide and curcumin, starting 2 weeks before the first pembrolizumab dose. Pembrolizumab is administered 3-weekly for a total of 6 cycles. Radiation (3 × 8 Gy) is given on days 1, 3 and 5 of the first pembrolizumab dose. The safety run-in consists of 6 patients. In total, 18 and 25 evaluable patients for cervical and endometrial carcinoma respectively are foreseen to enroll. No sample size is determined for uterine sarcoma due to its rarity. The primary objective is objective response rate at week 26 according to immune-related response criteria. Secondary objectives include safety, objective response rate at week 26 according to RECIST v1.1, best overall response, progression-free survival, overall survival and quality of life. Exploratory, translational research aims to evaluate immune biomarkers, extracellular vesicles, cell death biomarkers and the gut microbiome.. In this study, a combination of PD-1 blockade, radiation and immune/environmental-targeting compounds is tested, aiming to tackle the tumor microenvironment and induce anti-tumor immunity. Translational research is performed to discover biomarkers related to the mode of action of the combination.. EU Clinical Trials Register: EudraCT 2016-001569-97 , registered on 19-6-2017. Clinicaltrials.gov: NCT03192059 , registered on 19-6-2017.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Aspirin; Chemoradiotherapy; Curcumin; Cyclophosphamide; Drug Repositioning; Endometrial Neoplasms; Female; Humans; Immunotherapy; Lansoprazole; Neoplasm Recurrence, Local; Sarcoma; Survival Analysis; Treatment Outcome; Uterine Cervical Neoplasms; Vitamin D

Topics: Catheter Obstruction; Curcumin; Endometrial Neoplasms; Female; Humans; Infusions, Intravenous

Curcumin has been shown to have anticancer effects in a variety of tumors. However, there are fewer studies on the role of curcumin in endometrial carcinoma (EC). The purpose of this experiment was to examine the inhibitory effect of curcumin on endometrial carcinoma cells and ERK/c-Jun signaling pathway. We first predicted the mechanism of action of curcumin on endometrial carcinoma by network pharmacology. Then, we found that curcumin can decrease the cell viability of Ishikawa cells, inhibit the migration of cancer cells, induce apoptosis, and cause cell cycle arrest in the S phase. For molecular mechanism, curcumin reduced the mRNA expression levels of ERK2 and JUN genes and inhibited the phosphorylation of ERK and c-Jun. This suggests that curcumin inhibits the proliferation of endometrial carcinoma cells by downregulating ERK/c-Jun signaling pathway activity.

Topics: Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcumin; Down-Regulation; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Genes, jun; Humans; MAP Kinase Signaling System; Phosphorylation; Signal Transduction

Emerging evidence suggests that curcumin possesses chemopreventive properties against various cancers. However, its poor bioavailability limits its clinical application. In this study, we aimed to utilize encapsulation in liposomes (Lipo) as a strategy for the clinical administration of curcumin for endometrial carcinoma (EC).. Curcumin was encapsulated in a liposomal delivery system to prepare a formulation of liposomal curcumin (LC). EC cell lines Ishikawa and HEC-1 were treated with the compound and cell proliferation was measured using MTT assay. Hoechst 33258 staining assay and flow cytometry were used to detect apoptosis of the cells. Wound healing and cell invasion assays were employed to monitor cell motility. Underlying target signaling, such as NF-κB, caspases, and MMPs, were further studied via qRT-PCR and western blot. Thereafter, a zebrafish model was used to assess the toxicity of LC. Finally, a zebrafish transplantation tumor model of EC was grown and treated with LC. Tumors were monitored and harvested to study the expression of NF-κB.. The formation of LC was successfully developed with excellent purity and physical properties. In vitro, LC resulted in dose-dependent inhibition of proliferation, induction of apoptosis, and suppression of Ishikawa and HEC-1 cell motility. LC treatment also suppressed the activation and/or expression of NF-κB, caspase-3, and MMP-9. No demonstrable toxicity was found in the zebrafish model and tumors were suppressed after treatment with LC. PCR analysis also showed down-regulated expression of NF-κB.. LC was successfully prepared and played biological roles against EC probably through negative regulation of the NF-κB pathway in vitro and in vivo, which demonstrates its potential therapeutic effects in EC.

Topics: Animals; Apoptosis; Caspase 3; Cell Line, Tumor; Cell Movement; Cell Proliferation; Curcumin; Embryo, Nonmammalian; Endometrial Neoplasms; Female; Humans; Larva; Liposomes; Matrix Metalloproteinase 9; Microscopy, Fluorescence; NF-kappa B; Signal Transduction; Zebrafish

This study aims to investigate the effect of curcumin concentrations on the proliferation and invasion of endometrial cancer cells.. Endometrial cancer cells were cultured with 0, 15, and 30 μmol/l curcumin, and were divided into control group, low concentration group, and high concentration group. The treatment included the silencing and overexpression of MMP-2. The expression of MMP-2 and E-cadherin were detected by Western blot and the expression level changes were recorded after MMP-2 was silenced and overexpressed. Pearson's analysis was used to determine the relationship of curcumin concentration between MMP-2 mRNA. CCK-8 was used to detect the optical density of cancer cells in three groups. Transwell invasion assay was performed to analyze the invasion inhibition rate in the three groups.. Western blot and qPCR results: MMP-2 expression levels were lower and E-cadherin was higher in high concentration group than that in the low concentration group (p<0.01). MMP-2 protein and mRNA decreased after ShRNA and increased after overexpression (p<0.01). Pearson analysis revealed that the curcumin concentration was negatively correlated with the MMP-2 mRNA (r=-0.497, p=0.036). Cell optical density was lower with curcumin and the lowest was in high concentration group (p<0.01). After MMP-2 silencing, optical cell density decreased and this value increased after overexpression (p=0.000). Cell invasion results: Curcumin improves the rate of cell invasion (p<0.01). After silencing of MMP-2, cell invasion inhibition rate increased, while the invasion inhibition rate decreased after overexpression (p<0.01).. Curcumin can downregulate MMP-2, inhibit the proliferation and invasion of cancer cells.

Topics: Cadherins; Cell Line, Tumor; Cell Movement; Cell Proliferation; Curcumin; Endometrial Neoplasms; Female; Humans; Matrix Metalloproteinase 2; RNA Interference; RNA, Small Interfering

Although curcumin shows anti-proliferative and anti-inflammatory activities in various cancers, the effect of curcumin on cellular migration in endometrial adenocarcinoma cells remains to be understood. The current investigation was aimed to explore the anti-proliferative and anti-migratory effects of curcumin and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo experimental studies showed that curcumin inhibited the proliferation of endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells. Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed by scratch wound assay. In transwell migration studies, knock down of Slit-2 reversed the anti-migratory effect of curcumin in these cell lines. Curcumin significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and primary endometrial cancer cells while it down-regulated the expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the migration of endometrial cancer cells. In summary, we have demonstrated that curcumin has inhibitory effect on cellular migration via Slit-2 mediated down-regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These findings helped explore the role of Slit-2 in endometrial cancer cells.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Survival; Chemokine CXCL12; Chlorocebus aethiops; Curcumin; Down-Regulation; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Intercellular Signaling Peptides and Proteins; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred NOD; Mice, SCID; Nerve Tissue Proteins; Reactive Oxygen Species; Receptors, CXCR4; Signal Transduction; Vero Cells; Xenograft Model Antitumor Assays

Survivin is up-regulated in 83% of endometrial cancer leading to resistance development. As endometrial tumor advances, it also elicits chronic inflammation characterized by increased cytokine secretion and immune cells infiltration. The present study was designed to engineer mixed micellar curcumin loaded formulation for investigating survivin down-regulation, its anti-cancer and cytokine modulatory potential against endometrial cancer Ishikawa cells. Flory-Huggins interaction parameter (χ

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Curcumin; Cytokines; Down-Regulation; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Immunotherapy; Inhibitor of Apoptosis Proteins; Membrane Potential, Mitochondrial; Micelles; Rhodamines; Survivin

The current study aimed to explore the effect ofcurcumin on androgen receptor (AR) expression in endometrial carcinoma cells, as well as the underlying mechanisms.. Endometrial carcinoma cells were treated with curcumin (10, 50, and 100 micromol/l) for 12, 24, and 48 hours. Their growth curves were drawn using MTT assays and their apoptotic rates were determined using flow cytometry. The mRNA and protein expression of AR was detected using PCR and that of the Wnt signal related nucleopro- tein beta-cantenin was observed using western blot analysis. The influence of beta-cantenin on the action of curcumin was observed.. Curcumin downregulated the proliferation and apoptosis of human endometrial carcinoma cells in concentration and time-dependent manners. It downregulated the expression of AR and beta-cantenin in the cells. rWnt3a partially cancelled the effects of curcumin on the proliferation and apoptosis of human endometrial carcinoma cells as well as the AR expression-downregulating effect of curcumin.. Curcumin inhibits the proliferation and apoptosis of human endometrial carcinoma cells by downregulating their AR expression through the Wnt signal pathway.

Topics: Antineoplastic Agents; Apoptosis; beta Catenin; Cell Line, Tumor; Cell Proliferation; Curcumin; Down-Regulation; Endometrial Neoplasms; Female; Humans; Receptors, Androgen; RNA, Messenger; Wnt Signaling Pathway

Aberrant expression of potassium (K(+)) channels contributes to cancer cell proliferation and apoptosis, and K(+) channel blockers can inhibit cell proliferation. TREK-1 and -2 belong to the two-pore domain (K2P) superfamily. We report TREK-1 and -2 expression in ovarian cancer and normal ovaries, and the effects of TREK-1 modulators on cell proliferation and apoptosis.. The cellular localisation of TREK-1 and -2 was investigated by immunofluorescence in SKOV-3 and OVCAR-3 cell lines and in cultured ovarian surface epithelium and cancer. Channel expression in normal ovaries and cancer was quantified by western blotting. Immunohistochemical analysis demonstrated the association between channel expression and disease prognosis, stage, and grade. TREK-1 modulation of cell proliferation in the cell lines was investigated with the MTS-assay and the effect on apoptosis determined using flow cytometry.. Expression was identified in both cell lines, ovarian cancer (n = 22) and normal ovaries (n = 6). IHC demonstrated positive staining for TREK-1 and -2 in 95.7 % of tumours (n = 69) and 100 % of normal ovaries (n = 9). A reduction in cell proliferation (P < 0.05) was demonstrated at 96 h in SKOV-3 and OVCAR-3 cells incubated TREK-1 modulating agents. Curcumin caused a significant reduction in early apoptosis in SKOV-3 (P < 0.001) and OVCAR-3 (P < 0.0001) cells and a significant increase in late apoptosis in SKOV-3 (P < 0.01) and OVCAR-3 cells (P < 0.0001).. TREK-1 and -2 are expressed in normal ovaries and ovarian cancer. TREK-1 modulators have a significant effect on cell proliferation and apoptosis. We propose investigation of the therapeutic potential of TREK-1 blockers is warranted.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Blotting, Western; Case-Control Studies; Cell Proliferation; Cells, Cultured; Curcumin; Cystadenocarcinoma, Serous; Endometrial Neoplasms; Female; Flow Cytometry; Fluorescent Antibody Technique; Follow-Up Studies; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Grading; Ovarian Neoplasms; Ovary; Potassium Channels, Tandem Pore Domain; Prognosis; Survival Rate

The human endometrial epithelium is pivotal to menstrual cycle progression, implantation and early pregnancy. Endometrial function is directly regulated by local factors that include pH, oxygen tension and ion concentrations to generate an environment conducive to fertilization. A superfamily of potassium channels characterized by two-pore domains (K2P) and encoded by KCNK genes is implicated in the control of the cell resting membrane potential through the generation of leak currents and modulation by various physicochemical stimuli. The aims of the study were to determine the expression and function of K2P channel subtypes in proliferative and secretory phase endometrium obtained from normo-ovulatory women and in an endometrial cancer cell line. Using immunochemical methods, real-time qRT-PCR proliferation assays and electrophysiology. Our results demonstrate mRNA for several K2P channel subtypes in human endometrium with molecular expression of TREK-1 shown to be higher in proliferative than secretory phase endometrium (P < 0.001). The K2P channel blockers methanandamide, lidocaine, zinc and curcumin had antiproliferative effects (P < 0.01) in an endometrial epithelial cancer cell line indicating a role for TASK and TREK-1 channels in proliferation. Tetraethylammonium- and 4-aminopyridine-insensitive outwards currents were inhibited at all voltages by reducing extracellular pH from 7.4 to 6.6. Higher expression of TREK-1 expression in proliferative phase endometrium may, in part, underlie linked to increased cell division. The effects of pH and a lack of effect of non-specific channel blockers of voltage-gated potassium channels imply a role for K2P channels in the regulation of human endometrial function.

Topics: Adult; Arachidonic Acids; Cell Line, Tumor; Cell Proliferation; Curcumin; Endometrial Neoplasms; Endometrium; Epithelial Cells; Female; Gene Expression Regulation; Humans; Hydrogen-Ion Concentration; Lidocaine; Membrane Potentials; Menstrual Cycle; Nerve Tissue Proteins; Ovulation; Potassium Channel Blockers; Potassium Channels, Tandem Pore Domain; Primary Cell Culture; RNA, Messenger

Letrozole is an aromatase inhibitor that is used in the treatment of estrogen-sensitive tumors such as endometrial carcinoma, however, its therapeutic effect is still to be further improved. It is reported that curcumin has antitumor capability and can enhance the sensitivity of tumor cells to anticancer agents. This study was to investigate the inhibitory effect of letrozole combination with curcumin on the implanted endometrial tumor growth.. Nude mice were implanted with endometrial carcinoma RL-952 cells. All tumor-bearing mice were randomly divided into 5 groups: control(without treatment), Let(1) (letrozole, 1 microg/d), Let(10) (letrozole, 10 microg/d), Cur [ curcumin, 300 mg/kg.d)], and Let + Cur group [10microg/d letrozole + 50mg/ (kg.d) curcumin]. The tumor growth was monitored. Tumor cells apoptosis was detected in both control and treated groups. The expressions of bcl-2 mRNA and bcl-2 protein were detected using RT-PCR and Western blot, respectively.. Fifty mice were successfully implanted with the endometrial tumor. Treatment with letrozole markedly inhibited tumor growth; the inhibitory effect was further enhanced by the combination of letrozole and curcumin. The inhibitory rates in Let (1), Let (10), the Cur, and the Let + Cur groups were 15.95%, 22.49%, 21.57%, and 35.89%, respectively. Treatment with curcumin inhibited the expression of bcl-2 in tumor cells at the mRNA and protein levels. The apoptosis rates in the control group and the four experimental groups mentioned above were 16.97%, 32.90%, 35.80%, 34.16%, and 47.24%, respectively. Tumor cells apoptosis were observed in mice treated with either letrozole or curcumin; however, combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth.. Treatment with letrozole or curcumin could inhibit the xenografted endometrial tumor growth by inducing apoptosis in tumor cells. Combination of letrozole and curcumin further enhanced the inhibitory effect of tumor growth.

Topics: Adenocarcinoma; Animals; Apoptosis; Cell Cycle; Cell Line, Tumor; Curcumin; Drug Synergism; Endometrial Neoplasms; Female; Humans; Letrozole; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Nitriles; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Receptors, Estrogen; RNA, Messenger; Triazoles; Tumor Burden; Xenograft Model Antitumor Assays

Signal transducer and activator of transcription-3 (STAT-3) is constitutively activated in ovarian and endometrial cancers and is implicated in uncontrolled cell growth. Thus, its disruption could be an effective approach to control tumorigenesis. Curcumin is a dihydroxyphenolic compound, with proven anti-cancer efficacy in various cancer models. We examined the anti-tumor mechanism of curcumin on STAT-3 and on the negative regulators of STAT-3, including suppressors of cytokine signaling proteins (SOCS-1 and SOCS-3), protein inhibitors of activated STAT (PIAS-1 and PIAS-3), and SH2 domain-containing phosphatases (SHP-1 and SHP-2) in ovarian and endometrial cancer cell lines. Treatment of cancer cells with curcumin induced a dose- and time-dependent decrease of constitutive IL-6 expression and of constitutive and IL-6-induced STAT-3 phosphorylation, which is associated with decreased cell viability and increased cleavage of caspase-3. The inhibition of STAT-3 activation by curcumin was reversible, and phosphorylated STAT-3 levels returned to control levels 24 h after curcumin removal. Compared to normal cells baseline expression of SOCS-3 was high in cancer cells and a marked decrease in SOCS-3 expression was seen following curcumin treatment. Overexpression of SOCS-3 in curcumin-treated cells increased expression of phosphorylated STAT-3 and resulted in increased cell viability. Normal ovarian and endometrial cells exhibited high expression of PIAS-3 protein, whereas in cancer cells the expression was greatly reduced. Curcumin increased PIAS-3 expression in cancer cells. Of significance, siRNA-mediated knockdown of PIAS-3 overcomes the inhibitory effect of curcumin on STAT-3 phosphorylation and cell viability. In conclusion, curcumin suppresses JAK-STAT signaling via activation of PIAS-3, thus attenuating STAT-3 phosphorylation and tumor cell growth.

Topics: Apoptosis; Blotting, Western; Cell Line, Tumor; Curcumin; Endometrial Neoplasms; Female; Humans; Molecular Chaperones; Ovarian Neoplasms; Phosphorylation; Protein Inhibitors of Activated STAT; STAT3 Transcription Factor; Up-Regulation

Endometrial carcinoma is a malignant tumor in the uterus. Its current treatment is not satisfactory. The present study aimed to promote the inhibitory effect on the implanted endometrial tumor growth.. Nude mice were implanted with endometrial carcinoma. Some tumor-laden mice were treated with aromatase inhibitor letrozole and/or curcumin. The tumor growth was monitored. Tumor cell apoptosis was detected in both control and treated groups.. Fifty mice were successfully implanted with the endometrial tumor. Treatment with letrozole markedly inhibited the tumor growth; the inhibitor effect was further strengthened by combination with letrozole and curcumin. The results also showed that letrozole enhanced the expression of Bax and cytochrome c release and suppressed the expression of estrogen receptor in tumor cells. Treatment with curcumin inhibited the expression of Bcl-2 in tumor cells at the mRNA and protein levels. Tumor cell apoptosis was observed in mice treated with either letrozole or curcumin; however, combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth.. Treatment with either letrozole or curcumin could inhibit the xenografted endometrial tumor growth via inducing apoptosis in tumor cells. Combination of letrozole and curcumin further strengthened the inhibitory effect on tumor growth.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Carcinoma; Cell Line, Tumor; Cell Proliferation; Curcumin; Down-Regulation; Drug Synergism; Endometrial Neoplasms; Female; Humans; Letrozole; Mice; Mice, Inbred BALB C; Mice, Nude; Nitriles; Triazoles; Xenograft Model Antitumor Assays

Curcumin has been demonstrated to have an anti-tumor activity but the underlying molecular mechanisms are not fully uncovered. The present study was undertaken to determine the effect of curcumin on the expression of the proto-oncogene Ets-1 and the anti-apoptotic molecule Bcl-2 in human endometrial adenocarcinoma HEC-1-A cells.. Confluent HEC-1-A cells were treated with curcumin at various doses for 16 h or at 60 microM for various time points. At the end of the designated treatments, changes in cell morphology, DNA fragmentation and protein contents of Ets-1 and Bcl-2 were determined, respectively, by light microscopy, DNA laddering assay and Western blot analysis. As an initial step towards understanding whether Ets-1 was a possible up-stream regulator of Bcl-2 expression in HEC-1-A cells and if so, whether curcumin could attenuate the Ets-1-induced up-regulation of Bcl-2 expression, cells were transiently transfected with an Ets-1/GFP (Green Fluorescence Protein) fusion construct and the transfectants were treated with 60 microM curcumin for 16 h, followed by whole cell lysate preparation for Western blot analysis of Bcl-2 protein contents.. Curcumin induced apoptosis-like morphological changes and DNA degradation and decreased basal levels of Ets-1 and Bcl-2 protein contents in HEC-1-A cells in a time- and dose-dependent manner. Overexpression of Ets-1 in the cell resulted in an increase in Bcl-2 protein contents and that increase was attenuated by curcumin treatment.. Curcumin down-regulates Ets-1 and Bcl-2 expression and induces apoptosis in HEC-1-A cells, suggesting a novel molecular mechanism for the anti-tumor activity of curcumin.

Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Curcumin; Down-Regulation; Endometrial Neoplasms; Female; Humans; Proto-Oncogene Mas; Proto-Oncogene Protein c-ets-1; Proto-Oncogene Proteins c-bcl-2; Transfection; Up-Regulation

The adenomatous polyposis coli (APC) and mismatch repair (MMR) pathways are both involved in the tumorigenesis of hereditary colorectal cancers. Chemoprevention focuses on the APC pathway in the absence of information concerning MMR targets. This study compared the anticancer effects of sulindac, celecoxib, curcumin, and nifedipine in MMR-deficient cell lines, in order to determine the most appropriate chemopreventive agent for long-term use in patients with hereditary colorectal cancer.. Five human colorectal cell lines (SW480, HCT116, LoVo, SW48, and HCT15) and an endometrial cancer cell line (HEC-1-A) were used for susceptibility testing. Tests included assays for growth inhibition, cell-cycle arrest, and apoptosis.. Sulindac, celecoxib, curcumin, and nifedipine all displayed dose- and time-dependent anti-proliferation activities. Celecoxib was the most effective anti-proliferative agent, and increased the G0/G1 phase proportion in the cell cycle after treatment more significantly than the other agents in all cell lines. Curcumin displayed a more potent apoptosis-inducing activity than the other agents in treated cells.. The tested drugs were effective against colorectal and endometrial cancer cell lines. Celecoxib is more potent with fewer side effects than sulindac. Nifedipine's observed chemopreventive efficacy may complement its known therapeutic application in patients with hypertension.

Topics: Antineoplastic Agents; Apoptosis; Celecoxib; Cell Cycle; Cell Line, Tumor; Chemoprevention; Colorectal Neoplasms; Curcumin; Endometrial Neoplasms; Female; Humans; Nifedipine; Pyrazoles; Sulfonamides; Sulindac