• Journal of Microbiology and Biotechnology
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• v.28 no.4
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• pp.542-550
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• 2018

Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88-1) with the non-benzoquinone skeleton, obtained from genetically engineered Streptomyces hygroscopicus, was found to have anticancer activity against two human breast cancer cell lines. WK-88-1 produced concentration-dependent inhibition of cell proliferation, cell cycle arrest, and apoptosis in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cell lines. Detailed analysis showed that WK-88-1 downregulated some key cell cycle molecules (CDK1 and cyclin B1) and lead to $G_2/M$ cell cycle arrest. Further studies also showed that WK-88-1 could induce human breast cancer cell apoptosis by downregulating Hsp90 client proteins (Akt, p-Akt, IKK, c-Raf, and Bcl-2), decreasing the ATP level, increasing reactive oxygen species production, and lowering the mitochondrial membrane potential. Meanwhile, we discovered that WK-88-1 significantly decreased the levels of Her-2 and $ER-{\alpha}$ in MCF-7 cells but not in MDA-MB-231 cells. In addition, WK-88-1 significantly increased caspase-3, -8, and -9 activities and the cleavage of PARP in a concentration-dependent manner (with the exception of caspase-3 and PARP in MCF-7 cells). Taken together, our preliminary results suggest that WK-88-1 has the potential to play a role in breast cancer therapy.

• Journal of the Korea Society of Computer and Information
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• v.21 no.9
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• pp.101-106
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• 2016

The epidermal growth factor receptor(EGFR) protein kinase signaling is an important pathway in cancer development and recently reported that EGFR and its kinase domain molecules are mutated in various of cancers including head and neck cancer. Functional deregulation of EGFR due to mutations in coding exons and copy number amplification is the most common event in cancers, especially among receptor tyrosine kinases(TK). We have analyzed Korean oral squamous cell carcinomas (OSCC) cell lines for mutations in EGFRTK. Exons encoding the hot-spot regions in the TK domain of EGFR (exons 17 to 23) were amplified by using polymerase chain reaction(PCR) and sequenced directly. EGFR expression was also analyzed in 8 OSCC cell lines using western blotting. Data analysis of the EGFR exons 17 to 23 coding sequences did not show any mutations in the 8 OSCC cell lines that were analyzed. The absence of mutations indicate that protein overexpression might be responsible for activation rather than mutation.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.4
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• pp.239-245
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• 2022

Protein and peptide candidates are screened to apply therapeutic application as a drug. Ensuring that these candidates are delivered and maximized effectiveness is still challenging and a variety of studies are ongoing. As drug delivery system vehicles, cell-penetrating peptide (CPP) can deliver various kinds of cargo into the cell cytosol. In a previous study, we developed Ara27 CPP, which are a zinc knuckle family protein of Arabidopsis, and confirmed internalization in human dermal fibroblasts and human dental pulp stem cells at low concentration with short time treatment condition without any toxicity. Ara27, an amphipathic CPP, could be modified and utilized in the biomedical field excluding the risk of toxicity. Therefore, we would like to confirm the non-toxic induced penetrating ability of Ara27 in various cell lines. The purpose of this study was to screen the cell internalization ability of Ara27 in various cell lines and to confirm Ara27 as a promising core CPP structure. First, Ara27 was screened to confirm non-toxicity concentration. Then, fluorescence-labeled Ara27 was treated on human normal cell lines, cancer cell lines and animal cell lines to identify the cellular internalization of Ara27. Ara27 was well intracellular localized in all cell lines and the intensity of fluorescence was remarkably increased in time pass manner. These results indicate that Ara27 has the potential as a core structure for applications in various drug delivery systems.

• Journal of Nutrition and Health
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• v.49 no.2
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• pp.72-79
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• 2016

Purpose: The initiation of mandatory folic acid fortification using pteroylmonoglutamic acid (PteGlu) has reduced the rate of congenital malformations. However, it also appears to be responsible for several adverse effects, including increased cancer incidence. This may be related to physicho-chemical characteristics of PteGlu. This study examines the potential effect of high concentrations of PteGlu on a population subjected to mandatory folic acid fortification using an in vitro model. Methods: Caco-2 (colorectal cancer) and MCF7 (breast cancer) cell lines were cultured at 6 different PteGlu concentrations (0, 0.1, 1, 50, 250, and $500{\mu}g/ml$) for 6 days. Cell growth was determined using thiazolyl blue tetrazolium bromide assay. The genotype of dihydrofolate reductase 19bp deletion/insertion (DHFR 19-del) was also scored in cell lines using a restriction fragment length polymorphism technique to examine whether genetic variations may factor in cell proliferation. Results: PteGlu exhibited differential growth promoting properties between cell lines. Caco-2 cells did not show a significant growth difference at low concentrations compared to control, however, at higher concentrations, the growth showed a contrasting trend in the early experimental period, while MCF7 showed enhanced cell growth at all concentrations. The DHFR 19-del genotype differed in the two cell lines. Conclusions: Altered response to PteGlu by Caco-2 and MCF7 may reflect a tissue specific disease aetiology or genotype specific differential enzyme activity, for example by DHFR, to critical levels of PteGlu. As folic acid fortification is a blanket intervention, and DHFR and other enzyme activities vary between individuals, PteGlu intake may have an as yet undefined effect on health. These findings may be relevant when considering mandatory folic acid fortification for disease prevention.

• Preventive Nutrition and Food Science
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• v.5 no.1
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• pp.54-57
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• 2000

This study was designed to observe the anticancer activity of propolis on human rectal (HRT-18) and human colon (HCT-48) cancer cell lines in vitro, and on sarcoma-180 cells in vitro. The proliferation of HRT-18 and HCT-48 cancer cell lines was potently inhibited in proportion to the concentration of propolis. The survival time of the mice inoculated with sarcoma-180 cells was increased modestly by the administration of propolis compared to the control. Those observations suggest that propolis has anticancer effects against some of the cancer cell lines in vitro and in in vitro.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.132.1-132.1
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• 2003

Novel trans-ditrifluoroacetato, malonato-1, 4-butanediamine Pt(IV) complex, K104 was synthesized as a chemotherpeutic. The cytotoxicity of K104 against various human cancer cell lines were evaluated by MTS assay in vitro. The IC50 values of K104 ranged 15.83-25.83 $\mu\textrm{M}$, compared to CBCDA ranged 23.24-69.6 $\mu\textrm{M}$. Among several cancer cell lines, K104 showed more potent than CBCDA in colon cancer cell lines. (omitted)

• BMB Reports
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• v.56 no.7
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• pp.410-415
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• 2023

Breast cancer has become the most common cancer among women worldwide. Among breast cancers, metastatic breast cancer is associated with the highest mortality rate. Twist1, one of the epithelial-mesenchymal transition-regulating transcription factors, is known to promote the intravasation of breast cancer cells into metastatic sites. Therefore, targeting Twist1 to develop anti-cancer drugs might be a valuable strategy. In this study, LY-290181 dose-dependently inhibited migration, invasion, and multicellular tumor spheroid invasion in breast cancer cell lines. These anti-cancer effects of LY-290181 were mediated through the down-regulation of Twist1 protein levels. LY-290181 inhibited extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways. Therefore, our findings suggest that LY-290181 may serve as a basis for future research and development of an anti-cancer agent targeting metastatic cancers.

• Proceedings of the Korean Vacuum Society Conference
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• 2012.02a
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• pp.172-172
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• 2012

Non-thermal plasma has attracted medical researchers, since they showed higher apoptosis rate in cancer cells than normal cells. However, it is hard to conclude general cancer cell specific effect because comparison between normal and cancer cell activities after plasma treatment have not been reported yet. This research proposes a comparison of Dielectric Barrier Discharge (DBD) plasma effect on three normal cells lines and three cancer cells lines. We measured cell number, mitochondria activity (MTS assay) and amount of hydrogen peroxide (H2O2) for three days. The results show that the number of cancer cells decreased more than normal cells following of exposure time. On the other hand, mitochondria activities and amounts of H2O2 increased following of exposure time. In addition, we found that DBD plasma exposure on cell suspension in media and media only illustrated no difference in mitochondria activity, H2O2 quantity, and cell number. Thus, we can confirm higher apoptosis rate in cancer cells which is related to the reactive oxygen species (ROS) generated by DBD plasma. The related molecular mechanisms were investigated further.

• 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.16 no.14
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• pp.5977-5981
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• 2015

Background: Worldwide, breast cancer is the most common cancer diagnosed among women and a leading cause of cancer deaths. The age of onset in Iran has become reduced by a decade for unknown reasons. Herceptin, a humanized monoclonal antibody, is a target therapy for breast cancer cells with over expression of HER2-neu receptors, but it is an expensive drug with only 20% beneficial rate of survival. This study introduces a novel approach to enhance the efficacy of this drug through immunoconjugation of the antibody to botulinum toxin. Decreasing the cost and adverse effects of the antibody were secondary goals of this study. Materials and Methods: Botulinum toxin was conjugated with Herceptin using heterobifunctional cross linkers, succinimidyl acetylthiopropionate (SATP) and sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) according to the supplier's guidelines and tested on two breast cancer cell lines: SK-BR-3 and BT-474. Toxin and Herceptin were also used separately as controls. The cytotoxicity assay was also performed using the new bioconjugate on cultured cells with Alamar blue and a fluorescence plate reader. Results: Herceptin-Toxin bioconjugation significantly improved Herceptin efficacy on both breast cancer cell lines when compared to the control group. Conclusions: Toxin-Herceptin bioconjugation can be a potential candidate with increased efficiency for treating breast cancer patients with over expression of the HER2 receptor.