A retrospective comparison of outcome in IB2 and IIA cervical cancer patients treated with primary concurrent chemoradiation versus radical hysterectomy with or without tailored adjuvant therapy

OBJECTIVE: The aim of our study is to compare the overall survival (OS), progression-free survival (PFS), and treatment-related morbidities between primary concurrent chemoradiation therapy (CCRT) vs. radical hysterectomy (RH) with or without tailored adjuvant therapy in patients with stages IB2 and IIA cervical cancer. METHODS: This was a retrospective study of 113 patients with IB2 or IIA cervical cancer treated with either primary CCRT (n=49) or RH (n=64) with or without tailored adjuvant therapy between 2002 and 2011 at Keimyung University Dongsan Medical Center. Patients in RH group was divided into those undergoing surgery alone (n=26) and those undergoing surgery with adjuvant therapy (n=38). RESULTS: The median follow up period was 66 months. The 5-year OS by treatment modality was 88.7% for the 64 patients in the RH group and 72.8% for 49 patients in the CCRT group (P=0.044). The 5-year PFS was 82.3% and 65.6% after RH group and CCRT group (P=0.048), respectively. Grade 3–4 complication was less frequent after RH alone (7.7%) than RH with adjuvant therapy (34.2%) or CCRT group (28.6%) (P=0.047). CONCLUSION: The RH group seems to be superior to the CCRT group in oncologic outcomes. However, considering the selection bias including tumor size, lymph node meta, and parametrial invasion in pretreatment magnetic resonance imaging, both treatment modalities are reasonable and feasible in cervical cancer IB2 and IIA. It is important to choose the appropriate treatment modality considering the age and general condition of the patient. Randomized controlled study is needed to confirm the result of our study and determine the optimal treatment.

Salinomycin reduces stemness and induces apoptosis on human ovarian cancer stem cell / 부인종양

OBJECTIVE: Cancer stem cells (CSCs) represent a subpopulation of undifferentiated tumorigenic cells thought to be responsible for tumor initiation, maintenance, drug resistance, and metastasis. The role of CSCs in drug resistance and relapse of cancers could significantly affect outcomes of ovarian cancer patient. Therefore, therapies that target CSCs could be a promising approach for ovarian cancer treatment. The antibiotic salinomycin has recently been shown to deplete CSCs. In this study, we evaluated the effect of salinomycin on ovarian cancer stem cells (OCSCs), both alone and in combination with paclitaxel (PTX). METHODS: The CD44⁺CD117⁺CSCs were obtained from the ascitic fluid of patients with epithelial ovarian cancer by using an immune magnetic-activated cell sorting system. OCSCs were treated with PTX and salinomycin either singly or in combination. Cell viability and apoptosis assays were performed and spheroid-forming ability was measured. The expression of sex determining region Y-box 2 (SOX2) and octamer-binding transcription factor 3/4 (OCT3/4) mRNA was determined using reverse transcription polymerase chain reaction, and protein expression was observed using western blot analysis. RESULTS: Treatment with salinomycin alone reduced the stemness marker expression and spheroid-forming ability of OCSCs. Treatment with PTX alone did not decrease the viability of OCSCs. Treatment with a combination of salinomycin decreased the viability of OCSCs and promoted cell apoptosis. The enhancement of combination treatment was achieved through the apoptosis as determined by annexin V/propidium iodide (PI) staining, caspase-3 activity, and DNA fragmentation assay. CONCLUSION: Based on our findings, combining salinomycin with other anti-cancer therapeutic agents holds promise as an ovarian cancer treatment approach that can target OCSCs.

The effect of salinomycin on ovarian cancer stem-like cells

OBJECTIVE: The identification of cancer stem-like cells is a recent development in ovarian cancer. Compared to other cancer cells, cancer stem-like cells present more chemo-resistance and more aggressive characteristics. They play an important role in the recurrence and drug resistance of cancer. Therefore, the target therapy of cancer stem-like cell may become a promising and effective approach for ovarian cancer treatment. It may also help to provide novel diagnostic and therapeutic strategies. METHODS: The OVCAR3 cell line was cultured under serum-free conditions to produce floating spheres. The CD44⁺CD117⁺ cell line was isolated from the human ovarian cancer cell line OVCAR3 by using immune magnetic-activated cell sorting system. The expression of stemness genes such as OCT3/4, NANOG and SOX2 mRNA were determined by reverse transcription polymerase chain reaction. OVCAR3 parental and OVCAR3 CD44⁺CD117⁺ cells were grown in different doses of paclitaxel and salinomycin to evaluate the effect of salinomycin. And growth inhibition of OVCAR3 CD44+CD117+ cells by paclitaxel combined with salinomycin was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. RESULTS: Tumor spheroids generated from the OVCAR3 cell line are shown to have highly enriched CD44 and CD117 expression. Treatment with a combination of paclitaxel and salinomycin demonstrated growth inhibition of OVCAR3 CD44+CD117+ cells. CONCLUSION: The present study is a detailed investigation on the expression of CD44 and CD117 in cancer stem cells and evaluates their specific tumorigenic characteristics in ovarian cancer. This study also demonstrates significant growth inhibition of cancer stem-like cells by paclitaxel combined with salinomycin. Identification of these cancer stem-like cell markers and growth inhibition effect of salinomycin may be the next step to the development of novel target therapy in ovarian cancer.

Salinomycin inhibited cell proliferation and induced apoptosis in human uterine leiomyoma cells

OBJECTIVE: The aim of this study was to investigate the anti-proliferative effect of the salinomycin in cell proliferation and apoptosis in primary cultured human uterine leiomyoma cells. METHODS: Cell viability was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Caspase-3 activity assay and DNA fragmentation assay were performed to determine the effect of apoptosis. The expression of apoptosis regulatory-related proteins was evaluated by western blot. RESULTS: The cell viability and proliferation of uterine leiomyoma cells were significantly reduced by salinomycin treatment in a dose-dependent manner. DNA fragmentation assay results showed apoptotic cell death after salinomycin incubation. Salinomycin activated caspase-3, -8, and -9, causing apoptosis in uterine leiomyoma cells. Down-regulation of Bcl-2, XIAP, and FLIP with a concomitant increase in Bax, Fas, and DR5 were observed. CONCLUSION: These results provided the first evidence that salinomycin induce both intrinsic and extrinsic apoptosis. Therefore, salinomycin may be a promising chemopreventive and therapeutic agent against human uterine leiomyoma.

The Synergistic Apoptotic Interaction of Indole-3-Carbinol and Genistein with TRAIL on Endometrial Cancer Cells

Induction of apoptosis in target cells is a key mechanism by which chemotherapy promotes cell killing. The purpose of this study was to determine whether Indole-3-Carbinol (I3C) and Genistein in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce apoptosis in endometrial cancer cell (Ishikawa) and to assess apoptotic mechanism. The MTT assay and flow cytometry were performed to determine cell viability and cell cycle. The induction of apoptosis was measured by caspase-3 activity test, DNA fragmentation assay, annexin V binding assay and western blot analysis. There was no effect in cell growth inhibition and cell cycle progression alone or in two-combination. However, the treatment of I3C and Genistein followed by TRAIL showed significant cell death and marked increase in sub-G1 arrest. Three-combination treatment revealed elevated expression of DR4, DR5 and cleaved forms of caspase-3, caspase-8, PARP. The Flip was found down regulated. Moreover, increase in caspase-3 activity and DNA fragmentation indicated the induction of apoptosis. The results indicate that I3C and Genistein with TRAIL synergistically induced apoptosis via death receptor dependent pathway. Our findings might provide a new insight into the development of novel combination therapies against endometrial cancer.

A case of laparoscopic assisted suture of small bowel perforation / 대한산부인과내시경학회지

The use of laparoscopic surgical techniques is now being applied to a variety of operations traditionally performed in an open fashion. The indication for surgery included polyps, obstruction, bleeding, and perforation. Small bowel perforation was usually treated with open surgery, but now, laparoscopic-guided bowel surgery is technically feasible and should translate into shorter hospitalization and less patient discomfort. Recently, we successfully treated a case of laparoscopic assisted suture of small bowel perforation. Here we report this case with a brief review of literature.

Vaccination with a Human Papillomavirus (HPV)-16/18 AS04-Adjuvanted Cervical Cancer Vaccine in Korean Girls Aged 10-14 Years

The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.

Erratum

No abstract available.

Induction of growth inhibition and apoptosis in human endometrial cancer cells by histone deacetylase inhibitors / 대한산부인과학회지

OBJECTIVE: Endometrial cancer is the most common malignant tumor of the female genital tract. Its incidence has increased in recent years, making up 13% of female genital cancers. Nevertheless, the search for agents effective in the treatment of either advanced or recurrent endometrial cancer has been disappointing. Histone deacetylase inhibitors (HDACIs) were recently found to be well-tolerated in patients with hematologic and solid malignancies. HDACIs have been shown to inhibit cancer cell proliferation, stimulate apoptosis, and induce cell cycle arrest. Our purpose was to investigate the antiproliferative effects of the HDACIs (sodium butyrate and HDAC-I1) against endometrial cancer cell line (Hec 1A) and normal endometrial cell line (T-HESCs). METHODS: MTS reduction assay was carried out to determine the cell viability. Cell cycle analysis and DNA fragmentation assay was done by fluorescent activated cell sorter analysis. The expression of cell cycle-regulatory and apoptosis-related proteins were evaluated by Western blot. Caspase 3 and 7 activity were measured by immuno-flouorescent staining. RESULTS: Each sodium butyrate and HDAC-I1 induced growth inhibition in a dose and time dependent manner in endometrial cancer cells but did not induce growth inhibition in normal endometrial cells. Treatment with each drugs in endometrial cancer cells increased the percentage of cells in subG1 phase. The expression of p53, p21, p27, FAS, and FAS legand were increased and it was associated with increased p21 and p27 expression in a p53-dependent manner. Activation of caspase-3, 7, 8, 9 and down-regulation of Bcl-2, up-regulation of Bax, with concomitant increase in PARP cleavage, were observed. CONCLUSION: These results demonstrate that sodium butyrate induced growth inhibition and apoptosis in human endometrial cancer cells rising their possibility applicable against human endometrial cancers.

Intractable Postpartum Bleeding: A Comparison of the Retrospective Analysis of Angiographic Findings and Transcatheter Arterial Embolization According to Delivery Pattern

PURPOSE: We evaluated the technical aspect and efficacy of transcatheter arterial embolization (TAE) in cases of intractable postpartum bleeding by comparing the angiographic findings women patients according to their delivery pattern. MATERIALS AND METHODS: Between July of 2003 and March of 2008, 55 female patients were enrolled in this study. Of the 55 patients, 36 underwent a vaginal delivery (group 1), whereas 19 underwent a cesarean section delivery (group 2). We retrospectively evaluated the angiographic findings and the embolization technique between groups, using a Pearson Chi-Square test. Medical records and telephone interview findings were also reviewed to evaluate the efficacy of TAE and the outcome of fertility. RESULTS: Significantly greater positive angiographic findings were found in group 2 (63.2%) relative to group 1 (30.6%). For positive angiographic findings, except for AVM, the embolization was performed using coil or glue with gelfoam. For the negative angiographic findings or AVM, the gelfoam was the only embolic agent used. In all patients except for one, bleeding stopped after embolization. Major complications occurred in 2 patients only, and included uterine synechia and perforation. All patients except for one recovered after menstruation. In total, four patients became pregnant and one patient delivered a healthy infant. CONCLUSION: Positive angiographic findings requiring embolization with coil or glue, as well as gelfoam, were more commonly encountered in group 2 than in group 1. Based on the outcome of the study group, TAE is a safe and effective treatment for intractable postpartum bleeding and is also useful for preserving fertility.

A case of cervical branchial cleft cyst diagnosed with antenatal ultrasonography in fetus / 대한산부인과학회지

Cervical branchial cleft cysts are uncommon lesion that are developed from remnants of branchial apparatus in embryonal period. These cysts are found in infancy, childhood and adult by recurrent symptoms related to inflammation. It is difficult to find these cysts with antenatal ultrasonography and differential diagnosis from other cervical cysts is difficult too. We experienced a case of fetal cervical branchial cleft cyst that was found with antenatal ultrasonography and diagnosed with surgical biopsy, so we report our case with brief review of literatures.

Induction of apoptosis by Hibiscus protocatechuic acid in human uterine leiomyoma cells / 부인종양

OBJECTIVE: Hibiscus protocatechuic acid (PCA) is a food-derived polyphenol antioxidants used as a food additive and a traditional herbal medicine. In this study, PCA was to determine its effect on cell proliferation and cell cycle progression in primary cultured human uterine leiomyoma cells. METHODS: The effect of PCA on cell proliferation and cell cycle progression was examined in the primary cultured human uterine leiomyoma cells. MTT reduction assay was carried out to determine the viability of uterine leiomyoma cells. Cell cycle analysis for Hibiscus protocatechuic acid treated leiomyoma cells was done by FACS analysis. DNA fragmentation assay was performed to determine fragmentation rate by PCA in leiomyoma cells. Western blot analysis was done using anti pRB, anti-p21(cip1/waf1), anti-p53, anti-p27(kip1), anti-cyclinE, anti CDK2 antibodies to detect the presence and expression of these proteins in PCA treated myoma cells. RESULTS: PCA induced growth inhibition in a dose dependent manner, treatment with 5 mmol/L PCA blocked 80% cell growth. FACS results showed that there was increased the percentage of cells in sub G1. DNA fragmentation assay by ELISA was done to find the rate of apoptosis. Apoptosis took place but in a dose dependent manner. From Western blot analysis it revealed PCA induced the expression of p21(cip1/waf1) and p27(kip1) increasingly and was not mediated by p53. Caspase-7 pathway was activated and dephosphorylation of pRB took place. CONCLUSION: In Conclusions, PCA, a polyphenol antioxidant, inhibited cell proliferation and induced cell cycle arrest at sub G1 phase by enhancing the production of p21cip1/waf1 and p27kip1. These results indicate that PCA will be a promising agent for use in chemopreventive or therapeutics against human uterine leiomyoma.

Cyclin-Dependent Kinase Inhibitor p27(Kip1) Controls Growth and Cell Cycle Progression in Human Uterine Leiomyoma

The molecular mechanism of the cell-cycle machinery in uterine leiomyoma has not yet been fully elucidated. Among the various types of cell-cycle regulators, p27(Kip1)(p27) is considered to be a potent tumor suppressor. To provide further molecular basis for understanding the progression of uterine leiomyoma, our objective was to evaluate the expression level of p27 in normal myometrium and uterine leiomyoma tissue and its effect on cytogenic growth. Western blot analysis, real-time polymerase chain reaction (PCR) and immunohistochemical staining revealed that p27 protein and messenger RNA were down-regulated in uterine leiomyoma tissue and cultured cells compared to normal myometerium. Full-length human p27 cDNA was transferred using a replication-deficient recombinant adenoviral vector (Ad.p27) into uterine leiomyoma cells and evaluated the effect on cell proliferation. Transfection of Ad.p27 into uterine leiomyoma cells resulted in the induction of apoptosis, reduction in viability and proliferation of uterine leiomyoma cells. Our results suggest a new paradigm that down-regulated p27 protein expression is the possible underlying mechanism for the growth of uterine leiomyoma and over-expression of p27 induces cell death. This study provides better understanding of the control exerted by p27 in regulating growth and disease progression of uterine leiomyoma.

Treatment with sodium butyrate and rapamycin inhibit growth of human cervical cancer cells / 부인종양

OBJECTIVE: To evaluate whether mTOR inhibition by rapamycin can enhance the inhibitory effect of sodium butyrate, a histone deacetylase (HDAC) inhibitor on human cervical cancer cell line HeLa. METHODS: Cervical cancer cells (HeLa) were treated with sodium butyrate alone or in combination with rapamycin. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTS) assay and flow cytometry was performed to ascertain the effects of sodium butyrate and combinations of sodium butyrate with rapamycin. Expression of cell cycle related proteins were evaluated by Western blot analysis. RESULTS: As proven previously rapamycin, the mTOR inhibitor was effective in reducing the cell growth of cervical cancer cell line HeLa. Rapamycin and sodium butyrate induced growth inhibition in a dose dependent manner, with 100 nM/L rapamycin and 10 mM/L sodium butyrate blocked 78% cell growth. FACS analysis data substantiated the competence of rapamycin in inducing G1 arrest of mammalian cells, and this ability was greatly enhanced by the combination of sodium butyrate and rapamycin. The percentage of sub G1 fraction of cells was remarkably increased by the combination of sodium butyrate and rapamycin. Sodium butyrate in combination with rapamycin showed the increased expression of CDK inhibitors p21, p27, and dephosphorylation of Rb whereas the expression levels of cyclin A, cyclin D1 and cyclin B1 were reduced. CONCLUSION: The findings implicate that rapamycin could enhance the anti-cancer effect of sodium butyrate. Further in depth studies and in vitro studies would throw more light on the growth inhibitory mechanism and its potential use as therapeutic drugs of butyric acid and rapamycin.

Indole-3-carbinol and genistein inhibit growth of human uterine leiomyoma cells / 대한산부인과학회지

OBJECTIVE: To determine whether Indole-3-carbinol (I3C) can enhance the inhibitory effect of genistein on a human uterine leiomyoma cells. METHODS: Five uterine leiomyoma tissues were obtained from hysterectomies conducted on the benign diseases and cultured primarily. MTS reduction assay was carried out to determine the viability of human uterine leiomyoma cells. Cell cycle analysis for I3C and genistein treated human uterine leiomyoma cells was done by Fluorescent activated cell sorter (FACS) analysis. To detect the presence and expression of cell cycle related proteins was done by Western blot analysis. RESULTS: I3C and genistein induced growth inhibition in a dose dependent manner, treatment with 100 micro mol/L I3C and 100 micro mol/L genisten blocked 60% cell growth. FACS results showed that treatment with the I3C and genistein increased the percentage of cells in G2/M phase and decreased S phase. From Western blot analysis it revealed I3C and genistein induced the expression of p53, p21, and p27 increasing. Reduced expression of cyclin B1 and cyclin E were detected in treatment with I3C and genistein. The expression levels of these proteins correlate with G2/M cell cycle arrest. Activation of caspase pathway and fragmentation of PARP did not take place. CONCLUSIONS: These results demonstrate that I3C enhances genistein-mediated uterine leiomyoma cell growth inhibition through the cell cycle arrest at G2/M phase by decreasing the production of cyclin B1. Because of the synergistic effect of I3C and genistein, the potential exists for the therapeutic efficacy of each phytochemical when used in combination.

Augmentation of Sodium Butyrate-induced Apoptosis by Phosphatidylinositol 3-kinase Inhibition in the Human Cervical Cancer Cell-line / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Sodium butyrate (NaBT) is principally a histone deacetylase (HDAC) inhibitor, and it has the potential to arrest HPV-positive carcinoma cells at the G1 to S phase transition of the cell cycle. The aim of study was to determine whether phosphatidylinositol 3-kinase (PI3K) inhibition can enhance the inhibitory effect of NaBT on a human cervical cancer cell line (HeLa). MATERIALS AND METHODS: Cervical cancer cells (HeLa) were treated with NaBT alone or in combination with the PI3K inhibitors wortmannin or LY294002. Cell viability analysis and FACS analysis were carried out. The expressions of the cell cycle related proteins were evaluated by Western-blot analysis. RESULTS: Inhibition of PI3K enhanced NaBT-mediated apoptosis and this decreased the HeLa cell viability. Either wortmannin or LY294002, combined with NaBT, enhanced the activation of caspase 3 and caspase 9, and this enhanced the subsequent cleavage of poly (ADP-ribose) polymerase (PARP). Cervical cancer cells were arrested in the subG1 and G2/M phase, as was detected by FACS analysis. NaBT treatment in combination with PI3K inhibitors showed the increased expression of the CDK inhibitors p21(Cip1/Waf1) and p2(7Kip1), in a p53 dependent manner, and also the increased dephosphorylation of Rb whereas there was a reduction in the expression levels of cyclin A, cyclin D1 and cyclin B1. CONCLUSION: The results demonstrate that inhibition of PI3K enhances NaBT-mediated cervical cancer cell apoptosis through the activation of the caspase pathway. Moreover, these findings will support future investigation using the PI3K inhibitors in combination with adjuvant treatment for treating carcinoma of the cervix.

Maternal serum soluble Fas/Fas ligand level and expression of Fas/Fas ligand in placenta in preeclampsia / 대한산부인과학회지

OBJECTIVE: The aims of this study were designed to determine that serum soluble Fas and Fas ligand levels are altered in women with preeclampsia and HELLP syndrome, and to assess the expression of placental Fas and Fas ligand in women with preeclampsia and HELLP syndrome. METHODS: Blood samples were obtained from 31 women with normal pregnancy, 27 women with preeclampsia and five women with HELLP syndrome. Serum Fas/Fas ligand levels were measured by enzyme linked immunoassay. Immunohistochemical stain with polyclonal antibodies of Fas/Fas ligand were used to identify apoptosis. Mann-Whitney test, x2 test, Pearson correlation coefficients and multiple regression test were used for statistical analysis. RESULTS: Both soluble Fas ligand and Fas were detected in the sera of normal pregnancy, preeclampsia and HELLP syndrome. The mean serum level of soluble Fas was 5.83+/-0.37 U/mL in women with normal pregnancy, 10.84+/-0.93 U/mL in women with preeclampsia, and 10.79+/-00.69 U/mL in women with LELLP syndrome. The mean serum level of soluble Fas ligand was 0.59+/-0.03 U/mL in women with normal pregnancy, 0.51+/-0.21 U/mL in women with preeclampsia, and 0.60+/-0.01 U/mL in women with LELLP syndrome. The mean serum levels of soluble Fas were significantly higher in women with preeclampsia and HELLP syndrome than in women with normal pregnancy, but those of Fas ligand were no significant difference in each group. Apoptosis was conclusively demonstrated within placental tissue. The immunohistochemical analysis of Fas revealed diffuse immunoreactive stains were increased in women with preeclampsia than in women with normal pregnancy. But the immunohistochemical analysis of Fas ligand revealed diffuse immunoreactive stains were decreased in women with preeclampsia than in women with normal pregnancy. CONCLUSION: Placental apoptosis and altered expression of Fas and Fas ligand in trophoblast might influence the pathogenesis or pathophysiologic mechanism of preeclamsia. Elevated serum soluble Fas levels is associated with preeclampsia and HELLP syndrome. The source of elevated serum soluble Fas in preeclampsia and HELLP snydrome remains to be determined.

Induction of apoptosis in human cervical cancer cells by isoliquritizenin / 부인종양

OBJECTIVE: Isoliquritizenin (ISL) is a chalcone flavonoid, present in licorice, shallot and bean sprouts, has cancer preventing properties and often used in chinese medicine. In this study, ISL to determine its effect on cell proliferation and cell cycle progression in human cervical cancer cells were evaluated. METHODS: Cell viability assay was carried out to determine the viability of human cervical cancer cells. We tested the several experimental methods for verification and functional identification, including MTT assay, FACS analysis, DNA fragmentation assay, and Western blot analysis for ISL treated human cervical cancer cells (HeLa). RESULTS: ISL, induced growth inhibition in a dose dependent manner, treatment with 50 microM/L ISL blocked 50% cell growth. FACS results showed that there was no change in the S phase, but on the other hand ISL increased the percentage of cells in G1 phase. DNA fragmentation assay by ELISA was done to find the rate of apoptosis. Apoptosis took place but in a reduced manner. From Western blot analysis, it revealed ISL induced the expression of p21(Cip1/Waf1) and p27(kip1) but not mediated by p53. Caspase pathway was revealed and cleavage of PARP took place. CONCLUSION: ISL, a chalcone flavonoid, inhibited cell proliferation and induced cell cycle arrest at sub G1 by enhancing the production of p21(Cip1/Waf1) and p27(kip1). These results indicate that ISL will be a promising agent for use in chemopreventive or therapeutic against human cervical cancer cells.

Growth Inhibitory Effect of Resveratrol on Uterine Leiomyoma Cells / 대한산부인과학회지

OBJECTIVE: To examine the effect of resveratrol on cell proliferation and cell cycle progression in the human uterine leiomyoma cells. METHODS: MTS [3-(4,5-dimethylthiazol-2-yl)5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] reduction assay was carried out to determine the viability of human uterine leiomyoma cells. Western blot analysis was done using anti pRB, anti-p21cip1/waf1, anti-p53, anti-cyclin E, anti CDK2 antibodies to detect the presence and expression of these proteins in treatment with resveratrol. DNA fragmentation assay was done to find the rate of apoptosis. Cell cycle analysis for resveratrol treated in human uterine leiomyoma cells was done by FACS (fluorescence-activated cell sorter) analysis. RESULTS: Resveratrol induced growth inhibition in a dose dependent manner, treatment with 100 ?M/L resveratrol blocked 30% cell growth. From Western blot analysis it revealed resveratrol induced the expression of p53 increasing. Caspase pathway was activated and cleavage of PARP was occurred. Apoptosis took place but in a reduced manner. FACS results showed that resveratrol increased the percentage of cells in sub G1 phase. CONCLUSION: Resveratrol, a dietry phytoalexin, inhibited cell proliferation and induced cell cycle arrest at sub G1 by enhancing the production of p53. These results indicate that resveratrol will be a promising agent chemopreventives or therapeutics against human uterine leiomyoma cells.

Growth Inhibition of Human Uterine Leiomyoma Cells by Selective Estrogen Receptor Modulator / 대한산부인과학회잡지

OBJECTIVE: Our purpose was to evaluate potential efficacy of selective estrogen receptor modulators (raloxifene and tamoxifen) to human uterine leiomyoma cells. METHODS: The samples were collected from ten hysterectomized specimen. we evaluated the estrogen-responsive growth of human uterine leiomyoma and normal myometrial cells. The potential efficacy of Selective Estrogen Receptor Modulators (SERMs: raloxifene and tamoxifen) to human uterine leiomyoma cells were conducted by MTS, cell count assay and Western-blot. RESULTS: Human uterine leiomyoma and normal myometrial cells that expressed estrogen receptor (ER) showed increases the cell number in the presence of estrogen compared with ER negative uterine leiomyoma cells. Raloxifene and tamoxifen inhibited estrogen-stimulated proliferation of ER-containing human uterine leiomyoma and normal myometrial cells. Raloxifene was more effective in inhibiting estrogen-induced increases of cell number compared with tamoxifen. CONCLUSION: The effect of SERMs on leiomyoma was inhibited the cell proliferation without apoptosis or cell cycle arrest. These data suggest that SERM should be examined as candidate of nonsurgical therapeutic agents for uterine leiomyoma.