• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2179-2183
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• 2014

Background: In vitro, in vivo and clinical studies have demonstrated anti-cancer effects of deuterium depleted water (DDW). The nature of this agents action, cytotoxic or cytostatic, remains to be elucidated. We here aimed to address the point by examining effects on different cell lines. Materials and Methods: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) -based cytotoxicity analysis was conducted for human breast, stomach, colon, prostate cancer and glioblastoma multiforme cell lines as well as human dermal fibroblasts. The cell lines were treated with decreasing deuterium concentrations of DDW alone, paclitaxel alone and both. One way analysis of variance (ANOVA) was used for statistical analysis. Results: Treatment with different deuterium concentrations of DDW alone did not impose any significant inhibitory effects on growth of cell lines. Paclitaxel significantly decreased the survival fractions of all cell lines. DDW augmented paclitaxel inhibitory effects on breast, prostate, stomach cancer and glioblastoma cell lines, with influence being more pronounced in breast and prostate cases. Conclusions: DDW per se does not appear to have inhibitory effects on the assessed tumor cell lines as well as normal fibroblasts. As an adjuvant, however, DDW augmented inhibitory effects of paclitaxel and thus it could be considered as an adjuvant to conventional anticancer agents in future trials.

• BMB Reports
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• 제29권4호
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• pp.314-320
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• 1996

The effects of non-cytotoxic concentrations of tamoxifen, verapamil, and trifluoperazine on doxorubicin cytotoxicity in five human breast cancer cell lines were studied. A non-cytotoxic concentration of tamoxifen resulted in enhanced doxorubicin cytotoxicity in HTB-123, HTB-26, and MCF-7. In these three cell lines, a combination of tamoxifen with verapamil resulted in even more increased doxorubicin cytotoxicity. Addition of verapamil or trifluoperazine alone did not influence the doxorubicin cytotoxicity significantly. Only in HTB-19 did coincubation with verapamil increase the doxorubicin cytotoxicity. In HTB-123, combination of tamoxifen with trifluoperazine increased the doxorubicin cytotoxicity significantly. In the cell lines where co-incubation with tamoxifen increased doxorubicin sensitivity, high estrogen receptor expression was detected. However, HTB-20, where tamoxifen did not enhance doxorubicin action, was also estrogen receptor positive. None of the cell lines had multidrug resistance related drug efflux and drug retention was not increased by the treatment with tamoxifen and verapamil. Cell cycle traverses were not altered by incubation with tamoxifen, verapamil or combinations thereof. These observatlons suggest mechanism of non-cytotoxic concentrations of tamoxifen and verapamil on doxorubicin cytotoxicity may involve one or more other cellular processes besides those of interference of estrogen binding to its receptor, cell cycle perturbation, or drug efflux blocking.

• 약학회지
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• 제43권3호
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• pp.369-377
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• 1999

A new series of highly water soluble platinum(II) complexes {Pt(II)[1,3-bis(phenylthio) propane](trans- -1,2-diaminocyclohexane) (PC-1) and Pt(II)[1,3-bis-(phenythio)propane] cis-1,2-diaminocyclohexane(PC-2)} were synthesized, and characterized by their elemental analysis and by various spectroscopic techniques[infrared(IR), 13C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II) complexes was tested against P-388 and L-1210 mouse lymphocytic leukemia cell lines, PC-14 / P, PC-14/ADM and PC-14 / CDDP human pulmonary adenocarcinima, DU-145 human prostate carcinoma, HT-1376 human bladder carcinoma, ZR-75-1 human breast carcinoma, MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2.5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 showed active against L-1210, P-388 leukemia, human lung, stomach, prostate, bladder and breast cancer cell lines, and the antitumor activity of these compounds were comparable or superior to those of PC-2 and displatin. The nephrotoxicities of PC-1 and PC-2 were found quite less than that of cisplatin using MTT and [3H] thymidine uptake in rabbit proximal tubule cells and human kidney cortical cells. Based on these results, this novel platinum (II) complex compound (PC-1) represents a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.195-200
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• 2013

Secreted protein acidic and rich in cysteines-like protein 1 (SPARCL1), an extracellular matrix glycoprotein, has been implicated in the pathogenesis of several disorders including cancer. However, little is known about the expression and significance of SPARCL1 in human breast cancer. The aim of this study was to determine the expression pattern and clinicopathological significance of SPARCL1 in a Chinese breast cancer cohort. mRNA and protein expression of SPARCL1 in human breast cancer cell lines and breast cancer tissues was detected using the reverse transcription-polymerase chain reaction, real-time quantitative PCR, and Western blotting, respectively. Immunostaining of SPARCL1 in 282 Chinese breast cancer samples was examined and associations with clinicopathological parameters were analyzed. Compared to the positive expression in immortalized human breast epithelial cells, SPARCL1 was nearly absent in human breast cancer cell lines. Similarly, a significantly reduced expression of SPARCL1 was observed in human breast cancer tissues compared to that in normal breast epithelial tissues, for both mRNA and protein levels (P < 0.001). Immunohistochemical analysis showed that strong cytoplasmic immunostaining of SPARCL1 was observed in almost all normal breast samples (43/45) while moderate and strong immunostaining of SPARCL1 was only detected in 191 of 282 (67.7%) breast cancer cases. Moreover, down-regulation of SPARCL1 was significantly correlated with lymphatic metastasis (P = 0.020) and poor grade (P = 0.044). In conclusion, SPARCL1 may be involved in the breast tumorigenesis and serve as a promising target for therapy of breast cancer.

• 대한약침학회지
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• 제20권4호
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• pp.265-273
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• 2017

Objective: Orthosiphon pallidus (O. pallidus), which belongs to the Lamiaceae family, is a popular garden plant that is widely used for the treatment of various diseases, such as urinary lithiasis, fever, hepatitis, cancer and jaundice. The objective of the present work was to investigate the antioxidant free-radical scavenging and the anticancer activities of O. pallidus against human breast-cancer cell lines. Methods: The antioxidant activity of Orthosiphon pallidus aqueous extract (OPAE) was investigated using different models, such as the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the 2, 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) models, as were the $Fe^+$ chelation, the hydroxyl radical and superoxide radical scavenging, and total reducing power activities. The anticancer activities of the extract were determined by using the 3-(4, 5- dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) and the sulforhodamine (SRB) assays on the MCF-7 and the MDA-MB-231 cancer cell lines. Results: The aqueous Orthosiphon pallidus extract showed potent activity in in-vitro models. It significantly inhibited the scavenging of hydroxyl and superoxide radicals, but induced a remarkable $Fe^+$ chelation activity. For both cell lines, the percent cytotoxicity was found to increase steadily with increasing OPAE concentration up to $240{\mu}g/mL$. Conclusion: These results suggest that Orthosiphon pallidus has excellent antioxidant, antimicrobial, and anticancer activities against human breast-cancer cell lines.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.90-90
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47D and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 추계국제학술대회
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• pp.180-180
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER Positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47B and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

• Toxicological Research
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• 제21권1호
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• pp.77-85
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• 2005

Cadmium is an environmental pollutant exposed from contaminated foods or cigarette smoking and known to cause oxidative damage in organs. We investigated the cadmium-induced apoptosis and cell arrest in human breast cancer cells, MCF-7 cells and MDA-MB-231 cells. Obvious apoptotic cell death was shown in CdCl₂ 100 μM treatment for 12 hr, which were determined by DAPI staining and flow cytometric analysis. In cell cycle analysis, MCF-7 cells and MDA-MB-231 cells were arrested in S phase and G2/M phase respectively. These could be explained by the induction of cell cycle inhibitory protein, p21/sup Waf1/Cip1/ and p27/sup Kip1/, expression and reduction of cyclin/Cdk complexes in both cell lines. The decreased expression of cyclin A and Cdk2 in MCF-7 cells and cyclin B1 and Cdc2 in MDA-MB-231 cells were consistent with the flow cytometric observation. p-ERK expression was increased dose-dependent manner in both cell lines. It suggests that ERK MAPK pathway are involved in cadmium-induced cell cycle arrest and apoptosis. Moreover, cotreatment of zinc (100 μM, 12 hr) recovered the cadmium-induced cell arrest in both cells, which shows cadmium-induced oxidative stress mediates apoptosis and cell cycle arrest in human breast cancer cells.

• Journal of Nutrition and Health
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• 제38권8호
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• pp.656-662
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• 2005

Ginger (Zingiber of oficinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. Besides its extensive use as a spice, the rhizome of ginger has also been used in traditional oriental herbal medicine for the management of symptoms such as common cold, digestive disorders, rheumatism, neurologia, colic, and motion-sickness. The oleoresin from rhizomes of ginger contains [6] -gingerol (1- [4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) and its homologs as pungent ingredients that have been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, analgesic, antipyretic, antiheatotoxic, and cardiotonic effects. However, the effect of [6]-gingerol on cell proliferation in breast cancer cell are not currently well known. Therefore, in this study, we examined effect of [6]-gingerol on protein and mRNA expression associated with cell proliferation in MDA-MB-231 human breast. cancer cell lines. We cultured MDA-MB-231 cells in presence of 0, 2.5, 5 and $10{\mu}M$ of [6] -gingerol. [6]-Gingerol inhibited breast cancer cell growth in a dose-depenent manner as determined by MTT assay. ErbB2 and ErbB3 protein and mRNA expression were decreased dose-dependently in cells treated with [6]-gingerol (p<0.05). In addition, phosphorylated Akt levels and total hぉ levels were markedly decreased in cells treated with $2.5{\mu}M$ [6]-gingerol (p<0.05). In conclusion, we have shown that [6]-gingerol inhibits cell proliferation through ErbB2 and ErbB3, reduction in MDA-MB-231 human breast cancer cell lines.

• Biomolecules & Therapeutics
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• 제20권3호
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• pp.313-319
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• 2012

In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.