• 한국식품영양과학회지
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• 제31권4호
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• pp.691-695
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• 2002

한국산 솔잎을 가압.압착하여 얻은 수액을 증류한 솔잎 수액 증류액의 각종 암세포주에 대한 in uitro 세포독성을 시료액 대비 10배, 20배, 40배 희석군과 대조군에 대해 XTT법으로 실험한 결과, 쥐 백혈병 세포주인 L1210에 대해서는 76~89%, 쥐 육종암세포인 sarcoma 180에 대해서는 61~90%의 세포성장 억제효과를 나타내었다. 또한 인체의 monocyte-like cancer cell인 U937에 대해서는 56~81%, 인체 유방암 세포주인 T47D와 MDA-MB-231에서는 각기 12%, 또 다른 유방암 세포주인 MH7A에서는 64%, 인체 간암 세포주인 SNU-354에 대해서는 72%의 높은 세포 증식 억제효과를 나타내었다. 이로써 본 연구 시료인 솔잎 수액 증류액은 쥐 백혈병 세포주인 L1210, 쥐 육종암세포인 sarcoma 180, 인체 monocyte-like cancer cell인 U937, 인체 유방암 세포주인 MH7A, 인체 간암 세포주인 SNU-354에 대해 강한 세포독성을 갖는 것을 알 수 있었다. 이와 함께 솔잎 수액 증류액의 암세포에 대한 독성효과는 솔잎의 처리과정에 따라 다를 수 있으며, 또한 동일한 솔잎 수액증류액의 농도에서도 암세포주 종류에 따라 세포독성정도가 다름을 알 수 있었다. 따라서 최적 투여 농도와 적용 암세포주를 찾을 경우 새로운 항암제로 개발될 수 있음을 제시하였다.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.92-98
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• 2010

Breast cancer has been estimated as one of the most common causes of cancer death among women. The major cause of death from breast cancer is the metastatic spread of the disease from the primary tumor to distant sites in the body. Lycopene is one of the major carotenoids in fruits and vegetables including tomatoes. Epidemiological studies have shown that the dietary intake of lycopene is associated with decreased risk of cancer. Although mounting evidence shows the chemopreventive effect of lycopene, the role of lycopene in the prevention of metastatic potential of breast cancer has not been determined yet. In the present study, we investigated the inhibitory effect of lycopene on invasive and migratory phenotypes of two highly aggressive breast cancer cell lines, H-Ras-transformed MCF10A human breast epithelial cells (H-Ras MCF10A) and MDA-MB-231 human breast cancer cells. Here, we report that lycopene significantly inhibits invasion and migration as well as proliferation of H-Ras MCF10A and MDA-MB-231 cells. This study suggested an in vitro anti-cancer and anti-metastatic potential of lycopene. We also showed that activations of ERKs and Akt were inhibited by lycopene in H-Ras MCF10A cells, suggesting that the ERKs and Akt signaling pathways may be involved in lycopene-induced anti-proliferative and/or anti-invasive/migratory effects in these cells. Taken in conjunction with the fact that breast cancer metastasis is one of the most lethal malignancies in women, our findings may provide useful information for the application of lycopene in establishing strategy to prevent the metastatic breast cancer.

• Bulletin of the Korean Chemical Society
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• 제29권3호
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• pp.595-598
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• 2008

Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is a natural chemotherapeutic compound with diverse biological properties including an antitumor activity. Emodin, a specific inhibitor of the protein tyrosine kinase, has a number of cellular targets in related to it. Its inhibition activity affects the mammalian cell cycle regulation in specific oncogene. Practically, it has been proven to inhibit HER-2/neu tyrosine kinase expressing breast cancer cells as an anticancer agent. 2-[123I]iodoemodin has been synthesized and evaluated human breast cancer cells (MDA-MB-231, MCF-7, fibroblast as a control) which express basal levels of HER-2/neu tyrosine kinase to investigate its suitability as a breast cancer imaging agent and 2-iodoemodin has been synthesized as a standard compound. The radiochemical yield of the 2-[123I]iodoemodin was about 72% and its radiochemical purity was over 97% after purification. The radioactivity of the 2-[123I]iodoemodin was increased in a time dependent manner in both cell lines and the ratio of MDA-MB-231 and MCF7 to fibroblast was 2.9 and 1.7, respectively.

• 한국재료학회지
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• 제20권3호
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• pp.132-136
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• 2010

This study examined the biostability and drug delivery efficiency of g-$Fe_2O_3$ magnetic nanoparticles (GMNs) by cytotoxicity tests using various tumor cell lines and normal cell lines. The GMNs, approximately 20 nm in diameter, were prepared using a chemical coprecipitation technique, and coated with two surfactants to obtain a water-based product. The particle size of the GMNs loaded on hangamdan drugs (HGMNs) measured 20-50 nm in diameter. The characteristics of the particles were examined by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-TEM) and Raman spectrometer. The Raman spectrum of the GMNs showed three broad bands at 274, 612 and $771\;cm^1$. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay showed that the GMNs were non-toxic against human brain cancer cells (SH-SY5Y, T98), human cervical cancer cells (Hela, Siha), human liver cancer cells (HepG2), breast cancer cells (MCF-7), colon cancer cells (CaCO2), human neural stem cells (F3), adult mencenchymal stem cells (B10), human kidney stem cells (HEK293 cell), human prostate cancer (Du 145, PC3) and normal human fibroblasts (HS 68) tested. However, HGMNs were cytotoxic at 69.99% against the DU145 prostate cancer cell, and at 34.37% in the Hela cell. These results indicate that the GMNs were biostable and the HGMNs served as effective drug delivery vehicles.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6511-6516
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• 2012

Recently, we reported that an ethanol extract of Iris nertschinskia induces p53-dependent apoptosis in the MCF7 human breast cancer cell line. However, the detailed mechanisms were not fully explored. Here, we demonstrate another aspect of the activity of I. nertschinskia in breast cancer cells. We compared the response to an ethanol extract of I. nertschinskia in two different human breast cancer cell lines, Hs578Tand MDA-MB231, respectively with relatively low and high AKT1/2 activity by trypan blue exclusion assay and FACS analysis. Knockdown of endogenous AKT1 or AKT2 in breast cancer cells by RNA interference determined the sensitivity to I. nertschinskia ethanol extract compared to control cells. The I. nertschinskia ethanol extract induced cell death in a manner that depended on the level of phosphorylated AKT1/2 protein and was associated with a significant increase in the sub-G1 cell population, indicative of apoptosis. Our results indicate that an ethanol extract of I. nertschinskia differentially induces cell death in breast cancer cells depending on their level of phosphorylated AKT1/2.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.6089-6094
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• 2013

Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis. In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediated by alteration of gene expression profiles.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1241-1245
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• 2015

Background: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, $G47{\Delta}$, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of $G47{\Delta}$. Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with $G47{\Delta}$ at different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either $G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results: $G47{\Delta}$ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to $G47{\Delta}$, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to $G47{\Delta}$; $G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV $G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro. $G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, $G47{\Delta}$ may hold great promise for thyroid cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7919-7923
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• 2014

20(S)-Protopanaxadiol (PPD), a ginsenoside isolated from Pananx quinquefolium L., has been shown to inhibit growth and proliferation in several cancer cell lines. The aim of this study was to evaluate its anticancer activity in human breast cancer cells. MCF-7 cells were incubated with different concentrations of 20(S)-PPD and cytotoxicity was evaluated by MTT assay. Occurrence of apoptosis was detected by DAPI and Annexin V-FITC/PI double staining. Mitochondrial membrane potential was measured with Rhodamine 123. The Bcl-2 and Bax expression were determined by Western blot analysis. Caspase activity was measured by colorimetric assay. 20(S)-PPD dose-dependently inhibited cell proliferation in MCF-7 cells, with an $IC_{50}$ value of $33.3{\mu}M$ at 24h. MCF-7 cells treated with 20(S)-PPD presented typical apoptosis, as observed by morphological analysis in cell stained with DAPI. The percentages of annexin V-FITC positive cells were 8.92%, 17.8%, 24.5% and 30.5% in MCF-7 cells treated with 0, 15, 30 and $60{\mu}M$ of 20(S)-PPD, respectively. Moreover, 20(S)-PPD could induce mitochondrial membrane potential loss, up-regulate Bax expression and down-regulate Bcl-2 expression. These events paralleled activation of caspase-9, -3 and PARP cleavage. Apoptosis induced by 20(S)-PPD was blocked by z-VAD-fmk, a pan-caspase inhibitor, suggesting induction of caspase-mediated apoptotic cell death. In conclusion, the 20(S)-PPD investigated is able to inhibit cell proliferation and to induce cancer cell death by a caspase-mediated apoptosis pathway.

• 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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.139-139
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• 1998

Effects of TCDD and flavonoids on ethoxyresorufin deethylase in Hepa I cells and MCF-7 human breast cancer cells were examined. TCDD treatment have resulted in the stimulation of ethoxyresorufin deethylase activity based on fluorometry in Hepa I in dose and time dependent manner. 0.1 nM TCDD showed maximal stimulation of ethoxyresorufin deethylase activity and 24 hour treatment also showed maximal stimulation of ethoxyresorufin deethylase activity. In MCF-7 human breast cancer cells, untreated cells showed high basal level of ethoxyresorufin deethylase activity. TCDD treatment to MCF-7 cells resulted minor stimulation of ethoxyresorufin deethylase activity compared to that in Hepa I cells. Various chemicals were tested for ethoxyresorufin deethylase activity in both cell lines. Flavonoids, such as quercetin showed an inhibition of ethoxyresorufin deethylase activity that is stimulated with TCDD or 3-Methylcholanthrene. Estrogen and estrogen metabolites such as 16a-estriol also affects the ethoxyresorufin deethylase activity in MCF-7 cells.