• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.1
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• pp.169-180
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• 2005

Objective : Spatholobus Suberectus Dunn stems, Chinese vine plants, have been used for the relief of menstrual disorders and rheumatic arthralgia. In this study, we investigated the antitumor effect of Spatholobus Suberectus Dunn on cervical cancer in vitro. Methods : HeLA cervical cancer cell lines were used as targets. We examined the effect of water extract from Spatholobus Suberectus Dunn on cell proliferation, cell cycle regulation and cell cycle-regulating gene expression. Further, we investigated the apoptotic effects of Spatholobus Suberectus Dunn on cervical cancer cell lines. Results : Spatholobus Suberectus Dunn significantly inhibited the proliferation of cervical cancer cell lines in a dose-dependent and time dependent manner. Fluorescence activated cell sorter (FACS) analysis indicated that Spatholobus Suberectus Dunn induced G1 cell cycle arrest. Spatholobus Suberectus Dunn enhanced the expression of $p21^{waf1}$ and $p27^{kip1}$ with cell cycle arrest. Further, Spatholobus Suberectus Dunn stimulated apoptosis via caspase3 pathway. Conclusions : These findings suggest that Spatholobus Suberectus Dunn is a candidate agent for the treatment of cervical cancer. p21waf1 and $p21^{waf1}$ and $p27^{kip1}$ may play an important role in Spatholobus Suberectus Dunn-induced cell cycle arrest and cell growth inhibition.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4867-4871
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• 2012

Cervical cancer is a leading cause of morbidity and mortality in women worldwide. Although the human papillomavirus (HPV) is considered the major causative agent of cervical cancer, yet the viral infection alone is not sufficient for cancer progression. The etiopathogenesis of cervical cancer is indeed complex; a precise understanding of the complex cellular/molecular mechanisms underlying the initiation, progression and/or prevention of the uterine cervix is therefore essential. Autophagy is emerging as an important biological mechanism in targeting human cancers, including cervical cancer. Furthermore, autophagy, a process of cytoplasm and cellular organelle degradation in lysosomes, has been implicated in homeostasis. Autophagic flux may vary depending on the cell/tissue type, thereby altering cell fate under stress conditions leading to cell survival and/or cell death. Autophagy may in turn govern tumor metastasis and subsequent carcinogenesis. Inflammation is a known hallmark of cancer. Vascular insufficiency in tumors, including cervical tissue, leads to depletion of glucose and/or oxygen perturbing the osmotic mileu causing extracellular acidosis in the tumor microenvironment that may eventually result in autophagy. Thus, targeted manipulation of complex autophagic signaling may prove to be an innovative strategy in identification of clinically relevant biomarkers in cervical cancer in the near future.

• BMB Reports
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• v.57 no.2
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• pp.104-109
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• 2024

Gefitinib exerts anticancer effects on various types of cancer, such as lung, ovarian, breast, and colon cancers. However, the therapeutic effects of gefitinib on cervical cancer and the underlying mechanisms remain unclear. Thus, this study aimed to explore whether gefitinib can be used to treat cervical cancer and elucidate the underlying mechanisms. Results showed that gefitinib induced a caspase-dependent apoptosis of HeLa cells, which consequently became round and detached from the surface of the culture plate. Gefitinib induced the reorganization of actin cytoskeleton and downregulated the expression of p-FAK, integrin β1 and E-cadherin, which are important in cell-extracellular matrix adhesion and cell-cell interaction, respectively. Moreover, gefitinib hindered cell reattachment and spreading and suppressed interactions between detached cells in suspension, leading to poly (ADP-ribose) polymerase cleavage, a hallmark of apoptosis. It also induced detachment-induced apoptosis (anoikis) in C33A cells, another cervical cancer cell line. Taken together, these results suggest that gefitinib triggers anoikis in cervical cancer cells. Our findings may serve as a basis for broadening the range of anticancer drugs used to treat cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1403-1410
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• 2014

Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to be overexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin on HDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone $SiHa^R$ (derived from SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatin induced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibited HDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and $SiHa^R$, leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclin D1 and CDK4 were observed. Cisplatin resistance in $SiHa^R$ due to over-expression of MRP1 and Pgp1 was overcome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cell killing. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatory proteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, lowering the chemotherapeutic dose of the drug cisplatin.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4903-4906
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• 2013

Background: The purpose of this study was to determine proportional rates of cervical precancerous lesions and cancer, and associations with socio-demographic variables, HIV status, and CD4 cell count. Materials and Methods: A retrospective comparative study was conducted targeting the medical records of all women over age 18 that were diagnosed histologically through colposcopy with cervical precancerous lesions and cancer from 1 December 2011 to 30 November 2012. Results: A total of 313 patient records were used for data analysis. The average age was 39.1 (SD=2.04) years. More than a third (37.1%) of the patients had CIN III or cervical cancer. There was a significant association between age, CD4 cell count, HIV status, and cervical lesions (p<0.05). Age was found to be an influential predictor of cervical lesions (OR=0.67, 95%CI: 0.46-0.98). Conclusions: There exists an association between age and cervical lesions, with presentation of cervical precancerous lesions and cervical cancer at a younger age among HIV reactive patients. The National Guidelines should be brought in line with the National HIV Counseling and Testing Policy to offer Pap smears to all sexually active women that test HIV reactive during routine HIV Testing.

• KSBB Journal
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• v.16 no.6
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• pp.579-591
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• 2001

The cell growth inhibitor effect of cervical cancer cells was investigated by liposome mediated transfection (pRcCMVp53/lipofectin) and by transfection using adenovirus (AdCMVp57). The papilloma virus cancer cell lines we used in this study were HPV16 positive, having inhibiter gene, wild p53 gene, CaSki, SiHa, HPV18 positive HeLa, HeLaS3 and HPV negative C33A, HT3. LacZ gene of E.coli was used as the marker gene for the transfection efficiency. The effect on the inhibition of tumor cell growth was measured by cell count and cell viability though ELISA analysis and MTT assay. The inhibition of tumor cell growth was confirmed by measuring each assay for six days, comparing with the normal control cell growth. The cell growth of cervical cancer calls by transfection was significantly reduced and showed tittle differences among the cell lines. To eliminate the potential problem of Ad(adenovirus) contamination during rAAV production, rAAV can be produced by a triple transfection of vector plasmic, packaging plasmid, and adenovirus helper plasmid. To examine the helper functions of Ad plasmids on the production of rAAV vector, we carried out cotransfection of three plasmids, AAV vector, packaging construct, and Ad helper plasmids. The optimized transfection condition for calcium phosphate method is 25ug of total DNA per 10-cm-diameter plate of 293 cell. We found that rAAV yields peaked at 48hr after Ad infection. The titer of rAAV was measured by the dot blot analysis to measure the number of particles/ml based on the quantification of viral DNA. Recent1y, Kombucha(fungi) was identified as a very potent antileukefic agent. In the present study, effect of natural toxin(plankton) and Kombucha is PSP(GTXI-3, neoSTX), on various MTT assay cervical cancer cell line. Toxin(GTX 1-3, neoSTX) also inhibited the proliferation in primary cervical cancer calls in a dose-dependent toxin concentration. These results showed that toxin was very potent in inhibiting the proliferation of cervical cancer calls in vitro. Toxins and Kombuoha exhibited a dose dependent inhibition of cellular proliferation in cancer cell line.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3701-3704
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• 2012

Background: Cervical cancer is one of the most common cancers in developing countries and the second most common type of cancer in women globally. Several recent studies suggested a co factor role for Chlamydia trachomatis in pathogenesis of cervical cancer. This study aimed to evaluate existence of C. trachomatis DNA in pathologic blocks of patients with cervical cancer. Materials and methods: Seventy-six formaldehyde fixed paraffin embedded tissue specimens from patients with histologically proven history of cervical cancer as well as 150 blocks from healthy peoples were included in the present study. Thin slices were prepared from selected blocks followed by deparaffinization and DNA extraction; the presence of C. trachomatis DNA was examined by Taq Man real-time PCR. Results: Our TaqMan real time PCR assay with cervical specimens of patients with cervical cancer showed that there was no C. trachomatis DNA. Also, we found three positive specimens among our control group. Conclusion: It seems that based on results obtained from the specimens examined in the present study, there is no association between the presence of C. trachomatis DNA in cervical specimens and cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2313-2318
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• 2014

Peroxisome proliferator-activated receptor gamma (PPAR-${\gamma}$), a ligand-dependent nuclear transcription factor, has been found to widely exist in tumor tissues and plays an important role in affecting tumor cell growth. In this study, we investigated the effect of PPAR-${\gamma}$ on aspects of the cervical cancer malignant phenotype, such as cell proliferation and apoptosis. Cell growth assay, Western blotting, Annexin V and flow cytometry analysis consistently showed that treatment with troglitazone (TGZ, a PPAR-${\gamma}$ agonist) led to dose-dependent inhibition of cervical cancer cell growth through apoptosis, whereas T0070907 (another PPAR-${\gamma}$ antagonist) had no effect on Hela cell proliferation and apoptosis. Furthermore, we also detected the protein expression of p53, p21 and Mdm2 to explain the underlying mechanism of PPAR-${\gamma}$ on cellular apoptosis. Our work, finally, demonstrated the existence of the TGZ-PPAR-${\gamma}$-p53 signaling pathway to be a critical regulator of cell apoptosis. These results suggested that PPAR-${\gamma}$ may be a potential therapeutic target for cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1655-1659
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• 2016

Celecoxib, a selective inhibitor of COX-2, showed cytotoxic effects in many cancer cell lines including cervical cancer cells. This study investigated the effect of celecoxib on cell cycle arrest in HeLa cervical cancer cells through p53 expression. In vitro anticancer activity was determined with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A double staining method was applied to investigate the mechanism of cell death, cell cycling was analyzed by flow cytometryand immunocytochemistry was employed to stain p53 expression in cells. Celecoxib showed strong cytotoxic effects and induced apoptosis with an $IC_{50}$ value of $40{\mu}M$. It induced cell cycle arrest at G2/M phase by increasing level of p53 expression on HeLa cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3041-3044
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• 2013

Background: The non-steroidal anti-inflammatory drug (NSAID) aspirin (acetylsalicylic acid) is an inhibitor of cyclooxygenase enzymes. Recent studies have shown that aspirin could be used as an anti-tumor drug. Triptolide, the major compound extracted from the Chinese herb Tripteryglum wilfordii Hook.f, has now been shown that it can inhibit tumor growth. The aim of this study was to analyze the anti-tumor efficiency of aspirin and triptolide in cervical cancer cells. Methods: Viability of cervical cancer cell lines was assessed by the MTT method at various concentrations of aspirin and triptolide. Siha and HeLa cell apoptotic analysis was performed by flow cytometry. Real time-PCR and Western Blotting were used to analyze the expression of Bcl-2/Bax, Cyclin D1 and p16. Results: Viability in the combination group was significantly decreased as compared with either drug used alone. Expression change of Bcl-2/Bax, CyclinD1 and p16 appeared to play an important role in the synergistic killing effect on cervical cancer cell apoptosis. Conclusion: Aspirin and triptolide combination treatment may have synergistic anti-tumor effects on cervical cancer cells.