• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.3
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• pp.77-91
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• 2005

Purpose : Trichosanthis Radix is traditional medical herb which has been shown to inhibit tumor cell proliferation. In this study, the effects of Trichosanthis Radix extract were investigated on inducing growth inhibition and apoptosis of human uterine cervical carcinoma cells. Methods : Human uterine cervical carcinoma cells line, ME-180, was used for the study. The cells were treated with varying concentrations of Trichosanthis Radix extract. Cell growth and inhibitory rate were measured by MTT assay. Apoptosis induction was detected by fluorescence microscopy, DNA ladder formation and flow cytometry. Results : Trichosanthis Radix extract inhibited the growth of human uterine cervical carcinoma cells in a dose-dependent manner. It induced ME-180 cells to undergo apoptosis including fragmented nuclei and nucleosome-sized DNA fragmentation. Flow cytometric analysis showed the increasing rate of apoptotic cells by Trichosanthis Radix extract. Reduction of mitochondrial membrane potential and increase in caspase-3 activity and were found in ME-180 cells treated with Trichosanthis Radix extract. Conclusion : Our data suggest that Trichosanthis Radix extract inhibit the growth and proliferation of ME-180 cells by apoptotic induction and facilitates its activity via caspase-3 activation initiated by depolarization of mitochondria.

• Journal of the East Asian Society of Dietary Life
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• v.17 no.5
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• pp.710-718
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• 2007

This study was designed to investigate the effects of plum(Prunus salicina Lindl. cultivars 'Oishiwase', 'Formosa', and 'Soldam') extracts on the proliferation as well as inhibition of human epithelial cells(HaCaT), human cervical carcinoma (HeLa, SiHa, and C33A) cells, and human stomach adenocarcinoma(SNU 638) cells. Dried plum was sequentially extracted and fractionated by hexane(KC-01), chloroform(KC-02), ethyl acetate(KC-03), n-butanol(KC-04), water(KC-05), methanol(KC-6), and hot water extract(KC-07). The epithelial and cancer cells were exposed for 48 h to $50{\mu}g/mL$ of plum extract in vitro, and were then analysed by a sulforhodamin B(SRB) staining assay. The methanol extract(KCP-6) of 'Formosa' proliferated not only the HaCaT cells(147.3%), but also the cervical carcinoma C33A cells(167.8%). The ethyl acetate extract of 'Soldam'(KCJ-3) significantly reduced the proliferation rate of the HPV positive conical carcinoma cells, at 61.5% for the SiHa cells and 70.5% for the HeLa cells. In the C33A cells, which are HPV negative cervical carcinoma cells, the hexane fractions of 'Formosa'(KCP-1) and 'Oishiwase'(KCD-1) markedly suppressed proliferation activity at 20.4% and 61.7%, respectively. However, the proliferation rate of the normal epithelial cells(HaCaT cell) was not reduced the proliferation rate by KCJ-3, KCP-1, or KCD-1, There were no significant effects on proliferation of the stomach cancer cells(SNU 638) by any of the extracts or fractions of the plum cultivars. These results suggest that the anti-proliferative effects of the plum cultivars were selective to the cancer cell origin. In conclusion, we found that several plum cultivar extracts, especially, the ethyl acetate fraction of 'Soldam" and the hexane fraction of "Formosa', have anti-proliferative activity toward human cervical carcinoma cells. However, further investigation is needed to assess the molecular mechanisms that mediate the antiproliferation activities of the plum cultivars.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3429-3436
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• 2013

Cervical cancer is a major health problem worldwide and is the most frequent cause of cancer in women in India. Early detection and affordable drugs with clinical efficacy have to go hand-in-hand in order to comprehensibly address this serious health challenge. Plant-based drugs with potent anticancer effects should add to the efforts to find a cheap drug with limited clinical side effects. Keeping this very purpose in mind, an attempt has been made in this review to explore the potential of plant extracts or constituents known to exhibit antitumorigenic activity or exert cytotoxic effect in human cervical carcinoma cells. Alkaloids such as those isolated from C. vincetoxicum and T. Tanakae, naucleaorals A and B, isolated from the roots of N. orientalis, (6aR)-normecambroline, isolated from the bark of N. dealbata appear promising in different human cervical carcinoma cells with the $IC_{50}$ of 4.0-8 ${\mu}g/mL$. However, other compounds such as rhinacanthone and neolignans isolated from different plants are not far behind and kill cervical cancer cells at a very low concentrations. Among plant extracts or its constituents that enhance the effect of known anticancer drugs, noni, derived from the plant M. citrifolia perhaps is the best candidate. The cytotoxic potency and apoptotic index of cisplatin was found to significantly enhanced in combination with noni in different human cervical carcinoma cells and it therefore holds significance as promising herbal-based anticancer agent. However, efficacy needs to be further investigated in various cervical cell lines and more importantly, in in vivo cervical cancer models for possible use as an alternative and safe anticancer drug.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.2
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• pp.92-106
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• 2006

Purpose : To address the ability of Olibanum to induce cell death, we investigated the effect of olibanum on cell apoptosis. Twenty-four hours later, apoptosis occurred following olibanum exposure in a dose-dependent manner. Methods : We culture HeLa cell which is human metrocarcinoma cell in D-MEM included 10% fetal bovine serum(Hyclone Laboratories) below $37^{\circ}C$, 5% CO2. Then we observed apoptosis of log phage cell which is changed cultivation liquid 24 Hours periodically. Results : The treatment of BAPTA-AM regulated olibanum-induced apoptosis in HeLa human cervical carcinoma cells. The 24 hr-earlier -thapsigargin-pretreated cell showed the resistance against olibanum-induced apoptosis and the Ru360-mitochondrial uniporter-inhibited olibanum-induced apoptosis, too. It means that olibanum leads to the accumulation of calcium and the resultant apoptosis in HeLa cells. Immunoblotting data also shows that the expression of GRP78, ER stress marker protein, was induced by the olibanum. Bcl-2, anti-apototic protein, was decreased and that the expression of Bax, pro-apoptotic protein, was increased by the addition of olibanum. Interestingly, the olibanum increased the activity of caspase-8 as well as calpain cysteine pretense in HeLa cervical carcinoma cells. Calpain inhibitor-calpastatin as well as caspase-8C/A expression abrogated olibanum-induced apoptosis in the carcinoma cells. The inhibition of caspase-8 regulated olibanum-induced calpain activation but the inhibition of calpain did not have any effect on the caspase-8 activation in HeLa human cervical carcinoma cells. Conclusion : We conclude that olibanum induces the accumulation of calcium and the resultant apoptosis in which caspase-8 and calpain are involved.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8007-8018
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• 2014

Cervical cancer is the most common gynecologic malignancy worldwide and development of new therapeutic strategies and anticancer agents is an urgent priority. Plants have remained an important source in the search for novel cytotoxic compounds and several polyphenolic flavonoids possess antitumor properties. In this review article, data about potential anticarcinogenic activity of common natural flavonoids on various human cervical cancer cell lines are compiled and analyzed showing perspectives for the use of these secondary metabolites in the treatment of cervical carcinoma as well as in the development of novel chemotherapeutic drugs. Such anticancer effects of flavonoids seem to differentially depend on the cellular type and origin of cervical carcinoma creating possibilities for specific targeting in the future. Besides the cytotoxic activity per se, several flavonoids can also contribute to the increase in efficacy of conventional therapies rendering tumor cells more sensitive to standard chemotherapeutics and irradiation. Although the current knowledge is still rather scarce and further studies are certainly needed, it is clear that natural flavonoids may have a great potential to benefit cervical cancer patients.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.2
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• pp.77-91
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• 2006

Purpose : To address the ability of Dohaekseungkitang (DST: a commonly used herb formulation in Korea, Japan and China to have anti-cancer effect on cervical carcinoma), we investigated the effects of DST on programmed cell death (apoptosis) in HeLa human cervical carcinoma cells. Methods : We cultured HeLa cell which is human metrocarcinoma cell in D-MEM included 10% fetal bovine serum(Hyclone Laboratories) below $37^{\circ}C$, 5% CO2. Then we observed apoptosis of log phage cell which is changed cultivation liquid 24 Hours periodically. Results : After the treatment of DST for 48 hours, apoptosis occurred in a dose-dependent manner. In this study, we have shown that DST induces calpain and the associated caspase-8 and -9 activations. Apoptosis was prevented by pre-incubation of the cells with the calcium cHeLator-BAPTA-AM, calcium channel blocker-Nif edipine or Ryonidine agonist-Ryonidine peptide, implicating calcium in the apoptotic process. Ubiquitous calpains (mu- and m-calpain) have been repeatedly implicated in apoptosis, especially in calcium-related apoptosis. However this study showed 1hat either calpain inhibitor-calpastin or caspase-3 inhibitor-DEVD- did not blocked the herb formulation-induced apoptosis in HeLa human cervical carcinoma cells. D ST initiates a cell death pathway that is partially dependent of caspases. DST-induced apoptosis requires caspase-independent mechanism. Conclusion : We conclude that DST-induced calpain activation triggers the intrinsic apoptotic pathway in which caspase-independent mechanism is also involved.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8145-8147
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• 2016

Background: Atypical squamous cells of undetermined significance (ASCUS) feature a wide variety of cervical cells, including benign and malignant examples. The management of ASCUS is complicated. Guidelines for office gynecology in Japan recommend performing a high-risk human papillomavirus (HPV) test as a rule. The guidelines also recommend repeat cervical cytology after 6 and 12 months, or immediate colposcopy. The purpose of this study was to determine the clinical significance of ASCUS. Materials and Methods: Between January 2012 and December 2014, a total of 162 patients underwent cervical conization for cervical intraepithelial neoplasia grade 3 (CIN3), carcinoma in situ, squamous cell carcinoma, microinvasive squamous cell carcinoma, and adenocarcinoma in situ at our hospital. The results of cervical cytology prior to conization, the pathology after conization, and high-risk HPV testing were obtained from clinical records and analyzed retrospectively. Results: Based on cervical cytology, 31 (19.1%) of 162 patients were primarily diagnosed with ASCUS. Among these, 25 (80.6%) were positive for high-risk HPV, and the test results of the remaining 6 patients (19.4%) were uncertain. In the final pathological diagnosis after conization, 27 (87.1%) and 4 patients (12.9%) were diagnosed with CIN3 and carcinoma in situ, respectively. Conclusions: Although ASCUS is known as a low-risk abnormal cervical cytology, approximately 20% of patients who underwent cervical conization had ASCUS. The relationship between the cervical cytology of ASCUS and the final pathological results for CIN3 or invasive carcinoma should be investigated statistically. In cases of ASCUS, we recommend HPV tests or colposcopic examination rather than cytological follow-up, because of the risk of missing CIN3 or more advanced disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1513-1519
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• 2007

Yukwool-tang (YWT) is a traditional Chinese medicine, which has been used for patients suffering from a uterine disease in Oriental medicine. In the present study, it was examined the biochemical mechanisms of apoptosis by YWT in human cervical carcinoma HeLa cells. It was found that YWT could inhibit the cell growth of HeLa cells in a dose-dependent manner, which was associated with apoptotic cell death such as formation of apoptotic bodies and DNA fragmentation. Flow cytometry analysis confirmed that YWT treatment increased populations of apoptotic-sub-G1 phase of the cell cycle. We observed the p53-independent induction of p21 proteins, down-regulation of anti apoptotic Bcl-2 expression and proteolytic activation of caspase-3 in YWT-treated HeLa cells. YWT treatment also concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), phospholipase C-1 ($PLC{\gamma}1$), ${\beta}-catenin$ and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Taken together, these findings partially provide novel insights into the possible molecular mechanism of the anti-cancer activity of YWT.

• Archives of Pharmacal Research
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• v.18 no.6
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• pp.410-414
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• 1995

Adaptive response induced by low dese .gamma.-ray irradiation in human cervical carcinoma cells was examined. Cells were exposured to low dose of .gamma.-ray irradiation in human cervical carcinoma cells was examined. Cells were exposured to low dose of .gamma.-ray (1-cGy) followed by high doses of r-ray irradiation (0,1,2,3,5,7 and 9Gy for chlnogenic assay or 1.5Gy for micronucleus assay) with various time intervals. Survival fractions of cells in both low dose-irradiated and unirrated groups were analyzed by clonogenic assay. Surviva fractions of low dose-irradiated in cell survival was maximum when low and high dose irradiation time interval was 4 hr. Frequencies of micronuclei which is an indicative of chromosome aberration were also enutained from survival fractions analyzed by clonogenic assay, maximum when low and high dose irradiation time interval was 4hr. Frequencies of micronuclei which is an indicative of chromosome aberration were also enumerated in both low dose-irradiated and unirradiated groups. In consiststent with the result obtained from survival fractions analyzed by clonogenic assay, maximum reduction in frquencies of micronuclei was observed when low dose radiation was given 4 hr prior to high response to subsequent high dose .gamma.-ray irradiation in human cervical carcinomal cells. Our data suggest that one of the possible mechanisms of adaptive response induced by low dose rediation is the increase in repair of DNA double strand breaks in low dose radiation-adapted cells.

• BMB Reports
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• v.41 no.4
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• pp.294-299
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• 2008

Elevated expression of SMYD3 is a frequent genetic abnormality in several malignancies. Few studies knocking down SMYD3 expression in cervical carcinoma cells have been performed to date. In this paper, we established an inducible short hairpin RNA expression system to examine its role in maintaining the malignant phenotype of HeLa cells. After being induced by doxycycline, SMYD3 mRNA and protein expression were both reduced, and significant reductions in cell proliferation, colony formation and migration/invasion activity were observed in the SMYD3-silenced HeLa cells. The percentage of cells in sub-G1 was elevated and DNA ladder formation could be detected, indicating potent induction of apoptosis by SMYD3 knockdown. These findings imply that SMYD3 plays crucial roles in HeLa cell proliferation and migration/invasion, and that it may be a useful therapeutic target in human cervical carcinomas.