• Journal of Oral Medicine and Pain
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• v.35 no.3
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• pp.165-175
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• 2010

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent as well, when findings indicated the substance inhibited proliferation and induced differentiation of primitive neuroectocdermal tumor cells in vivo (Cinatl et al., 1997). Antitmor activity of VPA is associated with its targeting histone deacetylases. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-7, caspase-3 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or $25\;{\mu}M$ HS-1200 for 48 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of VPA and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.53 no.1
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• pp.75-84
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• 2008

Colored potatoes are an excellent source of dietary polyphenols including anthocyanins. Generally, anthocyanins from fruits and vegetables exhibit anti-carcinogenesis and anti-cancer properties in vitro test. This experiment was conducted to know the effects of colored potato extracts contained anthocyanins on antimutagenic activity and anticancer activity to six human cancer cell lines containing LNCaP (androgen-dependent) prostate cancer cells. Extracts of three colored potatoes ('Hongyoung', 'Jayoung' and 'Jasim') and the white potato ('Superior') cultivars were used in this study. The extracts of three colored potatoes inhibited the mutagenicities induced by direct mutagen such as 4-nitro-quinoline-1-oxide (4-NQO) and another indirect mutagens of bezo(a)pyrene (BaP). Also, the extracts of 'Hoyoung' and 'Jayoung' showed higher antimutagenic activity than 'Jasim' and 'Superior' against to direct or indirect mutagen on both strains of TA98 and TA100. The activity of growth-inhibitory of extract of four potato cultivars were screened by SRB (sulphorhodamine B) method on diverse human cancer cells representing different types of cancers. Among the extract of four potato cultivars, the extract of 'Jasim' showed moderate inhibition on proliferation of LNCaP, ACHN and MOLT-4F cells and did not inhibit the proliferation of other cancer cells. On the other hand, extract of 'Superior' did not inhibit the proliferation of any tested cancer cell lines. However, the extracts of 'Hongyoung and Jayoung' inhibited the proliferation of cancer cells with $GI_{50}$ values ranging from 2.5 to $30\;{\mu}g/mL$. On the basis of the $GI_{50}$ values, it is clear that LNCaP cells were more sensitive to extracts of colored potato cultivars than other cancer cells. The extract of 'Jayoung' at $30\;{\mu}g/mL$ were more active and inhibited cell proliferation, and induced apoptosis in LNCaP cells. This result revealed that the extracts of colored potatoes are expected to be good candidate for development into source of antimutagenic and anticancer agent.

• Journal of Food Hygiene and Safety
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• v.34 no.2
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• pp.183-190
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• 2019

Ursolic acid is recognized for various effects such as anti-cancer, antioxidant, and anti-inflammatory activity. In this study, we confirmed the anti-cancer effect of ursolic acid on human melanoma cancer cells, A375SM and A375P. Survival rate of the melanoma cells was confirmed by MTT assay and the proliferation rate was confirmed by wound healing assay. The rate of apoptotic bodies was confirmed by DAPI staining, and apoptosis rate was confirmed by flow cytometry. The induction of apoptosis protein was examined by western blotting according to the concentration of ursolic acid in melanoma cells. The survival and proliferation rates of melanoma cells were decreased according to the treatment concentrations of ursolic acid. DAPI staining showed that chromosomal condensation of melanoma cells was increased with increasing concentrations of ursolic acid, and increased apoptosis rate of melanoma cells by ursolic acid was confirmed by flow cytometry. We also confirmed by western blotting that cleaved-PARP and Bax were increased and Bcl-2 was decreased at $12{\mu}M$ concentration of uricolic acid in melanoma cells. This study was carried out at low concentrations of ursolic acid, 0 to $20{\mu}M$, and analyzed 24 h after treatment. As a result of this study, it is thought that ursolic acid has the anti-cancer effect through the regulation of apoptosis-related proteins in melanoma cells A375SM and A375P.

• Journal of Microbiology and Biotechnology
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• v.28 no.9
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• pp.1563-1572
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• 2018

Gold nanoparticles (AuNP) and their conjugates have been gaining a great deal of recognition in the medical field. Meanwhile, extended-spectrum ${\beta}$-lactamases (ESBL)-producing bacteria are also demonstrating a challenging problem for health care. The aim of this study was the biosynthesis of AuNP using Rosa damascenes petal extract and conjugation of ceftriaxone antibiotic (Cef-AuNP) in inhibiting ESBL-producing bacteria and study of in vitro anticancer activity. Characterization of the synthesized AuNP and Cef-AuNP was studied. ESBL-producing strains, Acinetobacter baumannii ACI1 and Pseudomonas aeruginosa PSE4 were used for testing the efficacy of Cef-AuNP. The cells of MCF-7 breast cancer were treated with previous AuNP and Cef-AuNP at different time intervals. Cytotoxicity effects of apoptosis and its molecular mechanism were evaluated. Ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy established the formation of AuNP and Cef-AuNP. Transmission electron microscope demonstrated that the formed nanoparticles were of different shapes with sizes of 15~35 nm and conjugation was established by a slight increase in size. Minimum inhibitory concentration (MIC) values of Cef-AuNP against tested strains were obtained as 3.6 and $4{\mu}g/ml$, respectively. Cef-AuNP demonstrated a decrease in the MIC of ceftriaxone down to more than 27 folds on the studied strains. The biosynthesized AuNP displayed apoptotic and time-dependent cytotoxic effects in the cells of MCF-7 at a concentration of $0.1{\mu}g/ml$ medium. The Cef-AuNP have low significant effects on MCF-7 cells. These results enhance the conjugating utility in old unresponsive ceftriaxone with AuNP to restore its efficiency against otherwise resistant bacterial pathogens. Additionally, AuNP may be used as an alternative chemotherapeutic treatment of MCF-7 cancer cells.

• IMMUNE NETWORK
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• v.16 no.1
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• pp.75-84
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• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

• Journal of the East Asian Society of Dietary Life
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• v.20 no.1
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• pp.30-36
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• 2010

This study was conducted to investigate the effects of blueberry extract on cell death, ROS and gene expression patterns associated with the anti-cancer activity in human breast cancer MCF7 cells. To accomplish this, 20 mg/mL concentration of blueberry extract was added to the cell culture for 0, 6, 12, 24 or 48 h, after which the effects were evaluated by various analyses. MTT assay showed that the cellular activities decreased rapidly during the first 12 h of treatment. During this period, dual staining with Hoechst33322 and propidium iodide also produced a similar trend in which the dead or dying cells increased sharply. Furthermore, evaluation of BrdU incorporation as an index for cell proliferation revealed a marked decrease during the first 12 h of treatment, suggesting that anticancer activity involves the inhibition of cell proliferation and induces cell death. ROS also increased according to the duration of the treatment, indicating intracellular accumulation is associated with the cell death. RT-PCR analysis revealed significant decreases in anti-apoptotic (Bax) and increases in pro-apoptotic gene expressions (Bci-2, caspase- 3, and 9) (p<0.05). Taken these together, blueberry extract induces ROS accumulation in MCF7 cells, causing inhibition of cell proliferation and eventually leading to cell death. This cell death was associated with apoptotic gene expression in blueberry-treated cells for up to 24 h.

• Journal of Life Science
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• v.24 no.3
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• pp.242-251
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• 2014

The objective of this study was to isolate a photosensitizer from Pueraria thunbergiana leaves that induces apoptosis in SK-HEP-1 cells. Column chromatography and thin layer chromatography were used to isolate active compounds from extracts of P. thunbergiana leaves. The structures of the isolated compounds were determined by 1D-NMR, 2D-NMR, and FAB-mass spectroscopy. A substance, named M4-3, was purified from the leaves of P. thunbergiana using various chromatography methods, and the absorbance of the substance was measured. The absorbance was highest at 410 nm, suggesting that the M4-3 substance was a different compound from chlorophyll a and b, which absorb at 410, 502, 533, and 607 nm. Further analyses revealed that the M4-3 compound was a $13^2$-hydoxy pheophorbide, a methyl ester with a molecular weight of 662. M4-3 was identified as a derivative compound of pheophorbide, with a structure that magnesium comes away from the porphyrin ring. The results of the analysis of the cytotoxicity of the M4-3 substance against the SK-HEP-1 cells revealed that it inhibited rates of cell growth by 40% and 80% at a concentration of 0.04 ${\mu}M$ and 0.08 ${\mu}M$, respectively. The M4-3 compound was found to be a photosensitizer for cytotoxicity because it was appeared only in light condition as examining activity in different irradiation conditions (light condition and nonlight condition) under the same concentration. Analysis of morphological changes in the cells following cell death induced by exposure to the M4-3 substance reveled representative phenomena of apoptosis (nuclear condensation, vesicle formation, and fragmentation of DNA). The induction of apoptosis was attributed to the compound's photodynamic activity.

• Journal of the Korean Wood Science and Technology
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• v.42 no.1
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• pp.68-77
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• 2014

A compound has been isolated from the methanol extract of Styrax japonica bark using conventional chromatographic methods including silica gel chromatography, TLC and HPLC. The molecular formula of Styraxlignolide F analyzed by spectrometric analyses using FAB-MS, NMR was found to be $C_{27}H_{34}O_{11}Na$. The cytotoxicity of the styralignolide F was showed 15.2% in $1.0mg/m{\ell}$ on human kidney cell (HEK 293). As anticancer activity of $CH_2Cl_2$ fraction, over 60% of AGS and MCF-7 cells were inhibited in concentration of $1.0mg/m{\ell}$. In the results of anticancer test using quantification of Bcl-2, $CH_2Cl_2$ fraction showed lower Bcl-2 and p53 expression than those of styraxlignolide F and other fractions. In apoptosis of human lung carcunoma cancer cell (A549), $CH_2Cl_2$ fraction showed the highest inhibition rate (46.9%) and styralignolide F was the next (43.5%). The $CH_2Cl_2$ fraction showed higher anti-cancer activities than isolated substance (styraxlignolide F), probably due to the crude extract showing synergic effects by other components.

• Journal of Life Science
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• v.27 no.2
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• pp.225-232
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• 2017

This study aimed to evaluate several biological activities of Pharbitis nil and to isolate an anticancer agent from its methanol extract. Pharbitis nil seeds were extracted with methanol (PNM). Then, PNM was fractionated into solvent layers such as ethyl acetate fraction (PNE), butanol fraction (PNB), and water fraction (PNW). The biological activities of the fractions were analyzed for tyrosinase inhibition, lipase inhibition, DPPH-free radical scavenging, and cell growth inhibition. PNM showed strong growth inhibition of prostate cancer PC-3 cells. PNM was subjected to Diaion HP-20 and eluted stepwise with 50%, 80%, and 100% methanol. Then, for activity-guided fraction, each fraction was analyzed for growth inhibition of prostate cancer PC-3 cells by using an MTT assay. Because the 100% fraction showed significantly strong inhibitory activity, the fraction was further separated in the reverse phase C18, which was eluted with 80% and 90% methanol. The 90% fraction was further subjected to Sephadex LH-20 using a mobile solvent of 100% methanol. Finally, the compound PN was partially purified for HPLC analysis. PN showed cell growth inhibitory activity and induced the apoptosis and cell cycle arrest of prostate cancer PC-3 cells, as measured by flow cytometry. The results together suggest that Pharbitis nil possesses various biological activities, especially the inhibitory activity for the proliferation of prostate cancer PC-3 cells, suggesting the possibility of its use as an anticancer agent.

• Korean Journal of Plant Resources
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• v.33 no.5
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• pp.460-466
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• 2020

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of leaves from Rodgersia podophylla against human colorectal cancer cells, HCT116. RPL dose-dependently decreased the cell viability through RPL-induced apoptosis in HCT116 cells. RPL induced inactivation the nuclear factor κB(NF-κB) through blocking IκB-α degradtion and P65 nuclear accumulation. The inhibition of GSK3β by LiCl attenuated RP-L-mediated NF-κB signaling inactivation. In addition, RP-L induced GSK3β activation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.