• Toxicological Research
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• v.32 no.3
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• pp.225-230
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• 2016

Zingiber officinale Roscoe has been widely used as a folk medicine to treat various diseases, including cancer. This study aims to re-examine the therapeutic potential of co-administration of natural products and cancer chemotherapeutics. Candidate material for this project, ${\alpha}$-zingiberene, was extracted from Zingiber officinale Roscoe, and ${\alpha}$-zingiberene makes up $35.02{\pm}0.30%$ of its total essential oil. ${\alpha}$-Zingiberene showed low $IC_{50}$ values, $60.6{\pm}3.6$, $46.2{\pm}0.6$, $172.0{\pm}6.6$, $80.3{\pm}6.6$ (${\mu}g/mL$) in HeLa, SiHa, MCF-7 and HL-60 cells each. These values are a little bit higher than $IC_{50}$ values of general essential oil in those cells. The treatment of ${\alpha}$-zingiberene produced nucleosomal DNA fragmentation in SiHa cells, and the percentage of sub-diploid cells increased in a concentration-dependent manner in SiHa cells, hallmark features of apoptosis. Mitochondrial cytochrome c activation and an in vitro caspase-3 activity assay demonstrated that the activation of caspases accompanies the apoptotic effect of ${\alpha}$-zingiberene, which mediates cell death. These results suggest that the apoptotic effect of ${\alpha}$-zingiberene on SiHa cells may converge caspase-3 activation through the release of mitochondrial cytochrome c into cytoplasm. It is considered that anti-proliferative effect of ${\alpha}$-zingiberene is a result of apoptotic effects, and ${\alpha}$-zingiberene is worth furthermore study to develop it as cancer chemotherapeutics.

• Journal of Microbiology and Biotechnology
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• v.31 no.4
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• pp.540-549
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• 2021

The Wnt/β-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/β-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, β-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/β-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/β-catenin pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.125-130
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• 2016

Nepeta cataria L. has been used in traditional medicine of some countries. Here the cytotoxic and apoptogenic activity of methanol extracts, n-hexane, dichloromethane, ethyl acetate, n-butanol, and acqueous extracts and the essential oil obtained from the aerial parts of the plant were evaluated with PC3, DU-145 and MCF-7 cell lines. Cell viability, histograms of PI stained fragmented DNA in apoptotic cells and Western blot analysis of proteins involved in the cascade of apoptosis were compared in all samples. Thirty components were identified as volatile, representing 99.7% of essential oil composition after GC-MS analysis of the oil obtained from aerial parts of the N. cataria by hydro-distillation. The major oil components of the essential oil were nepetalactone stereoisomers. Comparing IC50 values showed estrogen receptor positive PC3 cells were more sensitive to the cytotoxic effects of N. cataria in comparison with low hormone-receptor presenting DU-145 cells. Among multiple extracts and essential oils of the plant, only the ethyl acetate extract could significantly decrease cell viability in PC3 cells, in a concentration dependent manner. Ethyl acetate extract of N. cataria treated cells showed a sub-G1 peak in PC3 cells in a concentration dependent manner that indicates the involvement of an apoptotic process in ethyl acetate extract-induced cell death. Western blotting analysis showed that in PC3 cells treated with ethyl acetate (48 h) caspase 3 and PARP were cleaved to active forms. Overall, the results suggest that further analytical elucidation of N. cataria in respect to finding new cytotoxic chemicals with anti-tumor activity is warranted.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.257-261
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• 2016

Cancer causes cells to avoid death while being the second cause of death in the world itself. Damaged cells in the absence of apoptosis will increasingly amplify their inefficient genome. Of the two main apoptosis inducing pathways in cells, the first has p53 protein as the main initiating factor in the cascade. According to research results this protein s mutated in 50% of cancers and sointerest has cooncentrated on the second pathway that features death receptors. Among these receptors TRAIL1/DR5 is especially expressed in cancer cells. So targeting such receptors can initiate the apoptotic cascade in cells. Interestingly by substitution of activating ligands with antibodies as agonists, we could efficiently turn on the apoptosis pathway. First of all, three small peptides from the DR5 protein extracellular domain were synthesized and injected with two different kind of adjuvants (Fround and liposomal encapsulation) separately into mice at 15 day intervals. As a result, liposomal peptides induced the immune system more efficient than Frounds adjuvant and at the end point the antibodies which were obtained from liposomal peptide injection induced much more effective death. Liposomal formol could be used as an adjuvant in immunization utilizing small peptides. They carry, protect and deliver peptides very efficiently. In addition, small peptides of a certain size from the extracellular domain of DR5 proteins not only can induce immune system but also produce antibodies playing a remarkable anti-cancer roles against breast cancer cells (MCF-7).

• Journal of Biomedical Engineering Research
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• v.39 no.3
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• pp.140-145
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• 2018

Cancer is a major burden of human disease worldwide. Current chemotherapy has severe side effects because the drugs affect whole body nonspecifically. In addition, the drugs to reach cancer cells are very limited. Over the last two decades, Drug Delivery System (DDS) using nanoparticles has suggested promising results to improve current limitations. In this study, we prepared PLGA nanoparticles with different charge properties and observed their stability and internalization effect to cancer cells. Results using Dynamic Light Scattering (DLS) and Fourier Transform Infrared Spectroscopy (FTIR) confirmed the size and chemical composition of the nanoparticles. The stability of the nanoparticles in pH buffers were variable depending on charge properties. The nanoparticles showed different cytotoxicity and internalization effects to MCF-7 human breast cancer cells. In conclusion, we demonstrated the importance of delicately engineered nanoparticles for better DDS in cancer.

• Korean Journal of Plant Resources
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• v.33 no.6
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• pp.551-557
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• 2020

In this study, we were performed to elucidate the antioxidant and anticancer activity by leaves extracts from Acer tegmentosum (AT-L). In DPPH, ABTS radical scavenging activity, the AT-L revealed the high scavenging activity. Especially, the AT-L measured the highest ABTS radical scavenging activity, which is higher than ascorbic acid. The types of human cancer cells for evaluating the anticancer activity were colorectal cancer (SW480), prostate cancer (PC-3), breast cancer (MCF-7), pancreatic cancer (AsPC-1), lung cancer (A549) and liver cancer (HepG2). Human cancer cell viability was measured using MTT assay. Treatment of the AT-L decreased the cell viability and induced apoptosis in SW480 cells. These results suggest that extracts of the AT-L can be used as supplementary material for developing the natural antioxidant and anticancer drug for human cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7003-7006
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• 2015

Background: Nanoparticles of gold and silver are offering revolutionary changes in the field of cancer therapy. N-heterocyclic carbene (NHC) metal complexes possess diverse biological activities and are being investigated as potential chemotherapeutic agents. The purpose of this study was to examine the cytotoxicity and possible mechanisms of action of two types of newly synthesized nanofiber composites containing BIAN N-heterocyclic gold carbene complexes in two types of human cancer cells, namely breast cancer (MCF7) and liver cancer (HepG2) cells and also in normal human embryonic kidney cells (HEK 293). Materials and Methods: Cytotoxicity was assessed by MTT cell viability assay and oxidative stress by checking the total glutathione level. Results: Both compounds affected the cell survival of the tested cell lines at very low concentrations (IC50 values in the micro molar range) as compared to a well-known anti-cancer drug, 5 fluorouracil. A 60-80% depletion in total glutathione level was detected in treated cells. Conclusions: Reduction in total glutathione level is one of the biochemical pathways for the induction of oxidative stress which in turn could be a possible mechanism of action by which these compounds induce cytotoxicity in cancer cell lines. The in vitro toxicity towards cancer cells found here means that these molecules could be potential anticancer candidates.

• BMB Reports
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• v.52 no.12
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• pp.706-711
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• 2019

Cisplatin (Cis-DDP) is one of the most widely used anti-cancer drugs. It is applicable to many types of cancer, including lung, bladder, and breast cancer. However, its use is now limited because of drug resistance. p90 ribosomal S6 kinase (p90RSK) is one of the downstream effectors in the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathway and high expression of p90RSK is observed in human breast cancer tissues. Therefore, we investigated the role of p90RSK in the Cis-DDP resistance-related signaling pathway and epithelial-mesenchymal transition (EMT) in breast cancer cells. First, we discovered that MDA-MB-231 cells exhibited more Cis-DDP resistance than other breast cancer cells, including MCF-7 and BT549 cells. Cis-DDP increased p90RSK activation, whereas the inactivation of p90RSK using a small interfering RNA (siRNA) or dominant-negative kinase mutant plasmid overexpression significantly reduced Cis-DDP-induced cell proliferation and migration via the inhibition of matrix metallopeptidase (MMP)2 and MMP9 in MDA-MB-231 cells. In addition, p90RSK activation was involved in EMT via the upregulation of mRNA expression, including that of Snail, Twist, ZEB1, N-cadherin, and vimentin. We also investigated NF-κB, the upstream regulator of EMT markers, and discovered that Cis-DDP treatment led to NF-κB translocation in the nucleus as well as its promoter activity. Our results suggest that targeting p90RSK would be a good strategy to increase Cis-DDP sensitivity in triple-negative breast cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.427-436
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• 2012

Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction.Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product to be developed as not only the source of co-chemotherapeutic agents, but also phyto-estrogens. Therefore, further study needs to be conducted to explore the potential of citrus fruits in overcoming cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.3
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• pp.288-293
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• 2008

In this study, we investigated the anticancer activity of Makgeoly (MG). MG was fractionated into four fractions by using solvent partition method, affording hexane (MGH), methanol (MGM), butanol (MGB) and aquous (MGA) soluble fractions. We determined the cytotoxicity of these four fractions in four kinds of cancer cell lines, such as HepG2, MCF-7, B16-F10 and HT29 by MTT assay. Among the various fractions, the MGM showed the strongest cytotoxic effects on all cancer cell lines. The morphological changes such as membrane shrinking and blebbing of cells were also observed by MGM treatment in HepG2 cell. In addition, we observed quinone reductase (QR) activity stimulating effects in all fraction layers of MG on HepG2 cells. QR activity increased approximately 2.6 and 2.1 times in MGM and MGH treated HepG2 cell at $100{\mu}g/mL$, respectively, compared to that in control value. Although further studies are needed, the present work could suggest that the fin of MG has a potential to be used as a chemopreventive agent against cancer.