• 치위생과학회지
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• 제18권3호
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• pp.188-193
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• 2018

The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor $1{\alpha}$ and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.495-498
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• 2013

Epidermal growth factor receptor (EGFR) is over-expressed in several human cancers. This would suggest that inhibition of EGFR is a reasonable approach for cancer treatment. In this study we investigated EGFR blocking and its effects on the mediated signaling such as MAPK and STATb in HT29 cells. For this aim we used FITC-labeled EGFR antisense oligonucleotides encapsulated with PAMAM nanoparticles to inhibit EGFR expression. Cellular uptake of antisense was investigated by fluorescence microscopy and flow cytometry analysis. The effect of EGFR antisense on the expression of EGFR in HT29 cells was examined by real time PCR and Western blots, which showed that antisense encapsulated with PAMAM decreased the level of EGFR mRNA and protein. In addition, real time PCR results confirmed that EGFR inhibition had an effective role in the reduction of EGFR dependent downstream genes. In conclusion, EGFR antisense encapsulated with PAMAM nanoparticles down regulated EGFR and EGFR-mediated genes.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6581-6589
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• 2015

Background: Previously, stingless bee (Trigona spp.) products from East Kalimantan, Indonesia, were successfully screened for in vitro antiproliferative activity against human cancer derived cell lines. It was established that propolis from T. incisa presented the highest in vitro cytotoxicity against the SW620 colon cancer cell line (6% cell survival in $20{\mu}g/mL$). Materials and Methods: Propolis from T. incisa was extracted with methanol and further partitioned with n-hexane, ethyl acetate and methanol. The in vitro cytotoxicity of the extracts was assessed by the MTT assay against human colon (SW620), liver (Hep-G2), gastric (KATO-III), lung (Chago) and breast (BT474) cancer derived cell lines. The active fractions were further enriched by silica gel quick column, absorption and size exclusion chromatography. The purity of each fraction was checked by thin layer chromatography. Cytotoxicity in BT-474 cells induced by cardanol compared to doxorubicin were evaluated by MTT assay, induction of cell cycle arrest and cell death by flow cytometric analysis of propidium iodide and annexin-V stained cells. Results: A cardol isomer was found to be the major compound in one active fraction (F45) of T. incisa propolis, with a cytotoxicity against the SW620 ($IC_{50}$ of $4.51{\pm}0.76{\mu}g/mL$), KATO-III (IC50 of $6.06{\pm}0.39{\mu}g/mL$), Hep-G2 ($IC_{50}$ of $0.71{\pm}0.22{\mu}g/mL$), Chago I ($IC_{50}$ of $0.81{\pm}0.18{\mu}g/mL$) and BT474 (IC50 of $4.28{\pm}0.14{\mu}g/mL$) cell lines. Early apoptosis (programmed cell death) of SW620 cells was induced by the cardol containing F45 fraction at the $IC_{50}$ and $IC_{80}$ concentrations, respectively, within 2-6 h of incubation. In addition, the F45 fraction induced cell cycle arrest at the G1 subphase. Conclusions: Indonesian stingless bee (T. incisa) propolis had moderately potent in vitro anticancer activity on human cancer derived cell lines. Cardol or 5-pentadecyl resorcinol was identified as a major active compound and induced apoptosis in SW620 cells in an early period (${\leq}6h$) and cell cycle arrest at the G1 subphase. Thus, cardol is a potential candidate for cancer chemotherapy.

• Journal of Nutrition and Health
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• 제36권3호
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• pp.270-279
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• 2003

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid (LA) and exhibits anticarcinogenic activity in a variety of animal models. We have previously observed that CLA inhibited the growth of Caco-2 cells, a human colon adenocarcinoma cell line. The present study was performed to determine whether the growth inhibitory effect of CLA is related to change in secretion of IGF- II and/or IGF-binding proteins (IGFBPs) that have been shown to regulate Caco-2 cell proliferation by an autocrine mechanism. Cells were incubated in serum-free medium with various concentrations of CLA or linoleic acid (LA). Immunoblot analysis of 24-hours, serum-free, conditioned medium using a monoclonal anti-IGF-IIantibody revealed that Caco-2 cells secreted both mature 6,500 Mr and higher Mr forms of pro IGF-II. The levels of pro IGF-II and mature IGF-IIwere decreased by 43 $\pm$ 2% and 53 $\pm$ 6%, respectively by treatment with 50 $\mu$ M CLA. LA slightly increased pro IGF- II levels. Results from Northern blot analysis showed that CLA decreased IGF-II mRNA levels at 50 $\mu$ M concentration suggesting that CLA regulation of IGF-II protein expression occurs partly at the transcriptional level. Ligand blot analysis of conditioned media using 1251-IGF-II revealed that CLA slightly decreased IGFBP-2 levels and increased IGFBP-4 levels. We confirmed our previous results that CLA inhibited cell growth in a dose-dependent manner but LA slightly increased cell growth. Exogenous IGF-II mitigated the growth inhibitory effect of CLA. These results indicate that the growth inhibitory effect of CLA may be at least in part mediated by decreasing IGF-II and IGFBP-2 secretion and increasing IGFBP-4 secretion in Caco-2 cells.

• Advances in Traditional Medicine
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• 제7권4호
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• pp.336-340
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• 2007

Plants from the genus Centaurea (C.) (Family: Asteraceae alt. Compositae), widely distributed in Asia, Europe and North America, have traditionally been used in the treatment of various ailments. As a part of our on-going studies on the plants from the genus C. for their phytochemistry and biological activities, extracts of the seeds of Turkish endemic C. species, C. bornmuelleri and C. huber-morathii, were tested for their cytotoxicity towards the CaCo2 colon cancer cell line as well as for the toxicity towards the brine shrimps, using the MTT and the brine shrimp lethality assays, respectively. Among the extracts, the MeOH extract of these plants showed significant toxicity towards the brine shrimps ($LD_{50}=55.2{\times}10^{-2}\;and\;42.4{\times}10^{-2}mg/ml$, respectively). The MeOH extract of both C. species also inhibited the growth of CaCo2 colon cancer cells in the MTT assay ($IC_{50}$=29.9 and 33.0 g/ml, respectively). As the most prominent activities in both assays were observed with the MeOH extracts, it can be assumed that the compound(s) responsible for these activities are polar in nature.

• Preventive Nutrition and Food Science
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• 제5권2호
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• pp.114-118
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• 2000

The inhibitory effects of doenjang extracts and linoleic acid(LA) which was identified as one of the active compounds in doenjang on the growth of human cancer cells were studied, comparing to the actions on normal cells. Methanol extract and hexane fraction from doenjang exhibited the strong growth inhibitory effect on HT-29 human colon carcinoma cells. Inhibitory effects of chloroform, ethyl acetate, butanol and aqueous fractions on the cancer cells were observed, moderately or weakly. When cell counts of SNU-C$_1$human colon carcinoma cells were determined daily for 6 days, the inhibitory effect of hexane fraction on this cell line was higher than that of the methanol extract from doenjang. LA completely suppressed the growth of SNU-C$_1$cells after 4 days, while conjugated linoleic acid(CLA) resulted in 98% inhibition after 6 days. With the addition of LA and other free fatty acids such as stearic acid, oleic acid, linolenic acid and ${\gamma}$-linolenic acid (${\gamma}$-LnA) to the culture system, the growth of HT-29 cells and SNU-C$_1$cells was greatly suppressed after 6 days. Inhibitory effects of LA ${\gamma}$-LnA on the growth of these cells were stronger than other fatty acids. On the growth of AZ-521 human gastric carcinoma cells, LA and CLA completely cuppressed the growth of the cells after 4 days and 3 days, respectively. At the level of 0.001%~0.01% of LA, there was no cytotoxic effect on normal rat kidney cells and normal intestine human cells. These results showed that LA, a major active compound of doenjang, had strong inhibitory effects on the growth of human cancer cells without damaging normal cells.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.75-82
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• 1999

It has been reported that activation of sphingomyelin pathway and nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit the promotion of colon carcinoma. Ceramide, a metabolite of sphingomyelin, and indomethacin were shown to induce apoptosis in colon carcinoma cells. However, the mechanisms of ceramide- and indomethacin-induced apoptosis in the colon carcinoma cells are not clearly elucidated. Recent studys showed that indomethacin-induced apoptosis in colon cancer cells through the cyclooxygenase-independent pathways, and that may be mediated by generation of ceramide. In this study, we compared effects of ceramide and indomethacin on important modulators of apoptotic processes in HT29 cells, a human colon cancer cell line. Ceramide and indomethacin induced apoptosis dose- and time- dependently. Ceramide and indomethacin increased stress-activated protein kinase (SAPK) activity, and decreased mitogen-activated protein kinase (MAPK) activity. The expression of Bak was increased by the treatment of ceramide and indomethacin. The expression of other Bcl-2 related proteins (Mcl-1, $Bcl-X_L,$ Bax) which were known to be expressed in colon epithelial cells was not changed during the ceramide- and indomethacin-induced apoptosis. Our results suggest that ceramide and indomethacin share common mechanisms for induction of apoptosis in HT29 cells.

• 한국식품영양과학회지
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• 제39권1호
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• pp.36-41
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• 2010

상황버섯, 영지버섯 및 노루궁뎅이버섯 균사체로 발효된 인삼추출물이 암세포증식에 미치는 영향을 살펴보기 위하여 위암세포(MKN-45), 대장암세포(HCT116), 유방암세포(MCF-7), 폐암세포(NCIH460), 전립선암세포(PC-3) 및 간암세포(HepG2)에 농도별(0.25～1.5 mg/mL)로 처리하여 암세포 성장억제율을 측정하였다. 전립선암 세포에서의 암세포 증식억제 효과는 영지버섯 균사체발효 인삼추출물이 1.5 mg/mL 농도에서 3.07%로 가장 낮은 생존율을 나타내었으며, 상황버섯 균사체발효 인삼추출물이 35.05%, 노루궁뎅이버섯 균사체발효 인삼추출물이 44.29%의 생존율을 보였다. 폐암세포에 대한 세 가지 버섯균사체발효 인삼추출물의 1.5 mg/mL 농도에서 영지버섯 균사체발효 인삼추출물은 5.31%로 우수한 항암활성을 나타낸 반면, 상황버섯 균사체발효 인삼추출물이 53.52%, 노루궁뎅이버섯 균사체발효 인삼추출물이 35.27%의 생존율을 나타내었다. 이러한 결과로부터 영지버섯 균사체로 발효시킨 인삼추출물이 다른 균사체 인삼발효물보다 다양한 암세포에 대한 성장억제 효과가 우수함을 확인할 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.785-791
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• 2014

Crude extracts or phytochemicals obtained from some plants have potential anti-cancer properties. Teucrium persicum is an Iranian endemic plant belonging to the Lamiaceae family which has traditionally been used to relieve abdominal pains. However, the anti-cancer properties of this species of the Teucrium genus have not been investigated previously. In this study, we have used a highly invasive prostate cancer cell line, PC-3, which is an appropriate cell system to study anti-tumor properties of plants. A methanolic extract obtained from T persicum potently inhibited viability of PC-3 cells. The viability of SW480 colon and T47D breast cancer cells was also significantly decreased in the presence of the T persicum extract. Flow cytometry suggested that the reduction of cell viability was due to induction of apoptosis. In addition, the results of wound healing and gelatin zymography experiments supported anti-cell invasion activity of T persicum. Interestingly, sublethal concentrations of T persicum extract induced an epithelial-like morphology in a subpopulation of cells with an increase in E-Cadherin and ${\beta}$-Catenin protein levels at the cell membrane. These results strongly suggest that T persicum is a plant with very potent anti-tumor activity.

• Bulletin of the Korean Chemical Society
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• 제22권4호
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• pp.372-374
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• 2001

Three simple carboxamides incorporating the phenethylamine moiety have been isolated from strain XR-NC of a symbiotic bacterium Xenorhabdus nematophilus. Their structures were identified by spectroscopic data and synthesis. The compounds exhibited significant cytotoxicities against human cancer-cell line, viz. the gastric adenocarcinoma, colon adenocarcinoma and lung adenocarcinoma.