• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3281-3287
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• 2016

Bioactive compounds extracted from leaves and twigs of Goniothalamus griffithii include pinocembrin (PCN) and goniothalamin (GTN). The objectives of this study were to investigate the cytotoxic activities of PCN and GTN and their influence on molecular signaling for cell death in several human cancer cell lines compared to normal murine fibroblast NIH3T3 cells. GTN exhibited the most potent cytotoxicity against MCF-7 > HeLa > HepG2 > NIH3T3 cells with $IC_{50}$ values of 7.33, 14.8, 37.1 and $65.4{\mu}M$, respectively, whereas PCN was cytotoxic only to HepG2 cells with $IC_{50}$ values of ${\sim}80{\mu}M$. Apoptotic cell death was confirmed by staining the cells with annexin V-FITC and propidium iodide (PI) employing flow cytometry. Apoptosis was shown by externalization of phosphatidylserine in goniothalamin-treated MCF-7 cells in a dose response manner. Positive PI-stained cells with the typical morphology of apoptotic cells were increased dose-dependently. Furthermore, reduction of mitochondrial transmembrane potential was found in goniothalamin-treated MCF-7, HepG2 and HeLa cells. GTN treatment in MCF-7 increased caspase-3, -8 and -9 activities while GTN-induced HeLa cells showed an increase of both caspase-3 and -9 activities. But an increased caspase-8 activity was demonstrated in GTN- and PCN-treated MCF-7 and HepG2 cells, respectively. Taken together, GTN- and PCN-induced human cancer cell apoptosis was through different molecular mechanisms or signaling pathways, which might be due to different machineries in different types of cancer cells, as evidenced by the compound-modulated caspase activities in both intrinsic and/or extrinsic pathways.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2723-2726
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• 2016

Cancer represent one of the most serious health problems and major causes of death around the world. Many anticancer drugs in clinical use today are natural products or derived from natural sources. Withania somnifera (L.) Dunal is a small shrub widely distributed in many parts of the world including Saudi Arabia. The antiproliferative activities of the methanolic extract of W. somnifera leaves collected from Faifa mountains, southwest Saudi Arabia against MCF-7, HCT116 and HepH2 cell lines were investigated. The extract showed a strong antiproliferative activity against all cell lines with $IC_{50}$ values of 3.35, 2.19 and $1.89{\mu}g/ml$, respectively. Flow cytometry results showed that the extract arrested the cell cycle at S phase, and the increase in the caspase 3 activity suggested that the extract could induce cell apoptosis by a caspase mediated pathway. These results demonstrated that the methanolic extract of W. somnifera leaves collected from Faifa mountains has comparable strong antiproliferative activities to samples collected from different locations.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8617-8622
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• 2014

The goal of this study was to establish paclitaxel resistant MCF-7 cells, as in vitro model, to identify the molecular mechanisms leading to acquired chemoresistance in breast cancer cells. Resistant cells were developed by stepwise increasing exposure to paclitaxel. Gene expression levels of Bax and Bcl-2 along with protein levels of caspase-8 and caspase-9 were evaluated in two resistant cell lines (MCF-7/Pac64 and MCF-7/Pac5 nM). Morphological modifications in paclitaxel resistance cells were examined by light microscopy and fluorescence activated cell sorting (FACS). As an important indicator of resistance to chemotheraputic agents, the Bcl-2/Bax ratio showed a significant increase in both MCF-7/Pac5nM and MCF-7/Pac 64nM cells (p<0.001), while caspase-9 levels were decreased (p<0.001) and caspase-8 was increased (p<0.001). FACS analysis demonstrated that MCF-7/Pac64 cells were smaller than MCF-7 cells with no difference in their granularity. Our results support the idea that paclitaxel induces apoptosis in a mitochondrial-dependent manner. Identifying breast cancer patients with a higher Bcl-2/Bax ratio and caspase 9 level and then inhibiting the activity of these proteins may improve the efficacy of chemotheraputic agents.

• Biomolecules & Therapeutics
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• 제22권5호
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• pp.384-389
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• 2014

Adiponectin, an adipokine predominantly secreted from adipose tissue, exhibits diverse biological responses, including metabolism of glucose and lipid, and apoptosis in cancer cells. Recently, adiponectin has been shown to modulate autophagy as well. While emerging evidence has demonstrated that autophagy plays a role in the modulation of proliferation and apoptosis of cancer cells, the role of autophagy in apoptosis of cancer cell caused by adiponectin has not been explored. In the present study, we demonstrated that globular adiponectin (gAcrp) induces both apoptosis and autophagy in human hepatoma cell line (HepG2 cells) and breast cancer cells (MCF-7), as evidenced by increase in caspase-3 activity, Bax, microtubule-associated protein light chain 3-II (LC3 II) protein levels, and autophagosome formation. Interestingly, gene silencing of LC3B, an autophagy marker, significantly enhanced gAcrp-induced apoptosis in both HepG2 and MCF-7 cell lines, whereas induction of autophagy by rapamycin, an mTOR inhibitor, significantly prevented gAcrp-induced apoptosis in hepatoma cells HepG2. Furthermore, modulation of autophagy produced similar effects on gAcrp-induced Bax expression in HepG2 cells. These results implicate that induction of autophagy plays a regulatory role in adiponectin-induced apoptosis of cancer cells, and thus inhibition of autophagy would be a novel promising target to enhance the efficiency of cancer cell apoptosis by adiponectin.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5865-5869
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• 2012

RHOXF1 has been shown to be expressed in embryonic stem cells, adult germline stem cells and some cancer lines. It has been proposed as a candidate gene to encode transcription factors regulating downstream genes in the human testis with antiapoptotic effects. Its expression in cancer cell lines has implied a similar role in the process of tumorigenesis. The human breast cancer cell lines MDA-MB-231 and MCF-7 were cultured in DMEM medium and transfected with a pGFP-V-RS plasmid bearing an RHOXF1 specific shRNA. Quantitative real-time RT-PCR was performed for RHOXF1, CASP8, BCL2 and HPRT genes. Decreased RHOXF1 expression was confirmed in cells after transfection. shRNA knock down of RHOXF1 resulted in significantly decreased BCL2 expression in both cell lines but no change in CASP8 expression. shRNA targeting RHOXF1 was shown to specifically mediate RHOXF1 gene silencing, so RHOXF1 can mediate transcriptional activation of the BCL2 in cancers and may render tumor cells resistant to apoptotic cell death induced by anticancer therapy. shRNA mediated knock down of RHOXF1 can be effective in induction of apoptotic pathway in cancer cells via BCL2 downregulation, so it can have potential therapeutic utility for human breast cancer.

• 한국식품영양과학회지
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• 제34권10호
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• pp.1514-1519
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• 2005

본 실험은 홍조해조류의 하나인 김을 메탄올로 추출 후 각 용매별로 다시 분획하여 암세포 성장억제 효과와 QR유도활성 효과 등 생리활성을 연구하였다. 김을 이용하여 4종의 암세포주 C6, HepG2, MCF-7및 HT-29 세포주에 대한 암세포 증식억제 실험을 한 결과 사용한 4종의 암세포주에서 모두 시료첨가 농도에 의존적으로 증식저지 효과가 나타났고, 특히 김의 hexan 분획물에서 가장 높은 암세포 성장 억제효과를 나타내었다. 그리고 본 시료는 신경종양, 간암 및 여성암의 대표적인 유방암세포의 성장억제효과가 탁월하였다. 또한, 사용한 4가지 암세포주중 유일하게 quinone reductase를 가지고 있는 HepG2를 이용한 암 예방지표인 quinone reductase 효소 유도 활성 여부를 측정한 결과 분획물 첨가농도를 50, 100 및 150 g/mL로 첨가하였을 때 PTMH의 첨가농도 50 ${\mu}g/mL$에서 대조군에 비해 약 1.5배 이상의 높은 QR 유도효과를 나타내었고 최종농도 150 ${\mu}g/mL$에서는 약 6.6배의 높은 암 예방 QR 유도효과를 나타내었다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.136-136
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• 2002

Experiments were carried out to determine the role of Raf-1 kinase in the development of drug resistance and apoptosis induced by paclitaxel. In the present study, paclitaxel sensitivity, Raf-1 activity and MAPKs activation were compared in 2 cell lines: parental human breast cancer cells and its drug resistant variant (MCF-7/Adr) cells.(omitted)

• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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• pp.4965-4971
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• 2016

Objective: Breast cancer is global female health problem worldwide. Most of the currently used agents for breast cancer treatment have toxic side-effects. Ginseng root, an oriental medicine, has many health benefits and may exhibit direct anti-cancer properties. This study was performed to assess the effects of ginseng on breast cancer cell lines. Materials and Methods: Cytotoxicity of ginseng extract was measured by MTT assay after exposure of MDA-MB-231, MCF-10A and MCF-7 breast cancer cells to concentrations of 0.25, 0.5, 1, 1.5, 2 and 2.5 mg/well. Expression levels of p21WAF, p16INK4A, Bcl-2, Bax and P53 genes were analyzed by quantitative real time PCR. Results: The treatment resulted in inhibition of cell proliferation in a dose-and time-dependent manner. p53, p21WAF1and p16INK4A expression levels were up-regulated in ginseng treated MDA-MB-231 and MCF-7 cancer cells compared to untreated controls and in MCF-10A cells. The expression levels of Bcl2 in the MDA-MB-231 and MCF-7 cells were down-regulated. In contrast, that of Bax was significantly up-regulated. Conclusion: The results of this study revealed that ginseng may inhibit breast cancer cell growth by activation of the apoptotic pathway.

• 한국식품영양과학회지
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• 제31권1호
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• pp.136-142
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• 2002

본 연구는 다른 산채류에 비해 칼슘이 칼슘이 특히 많은 우수한 식품으로 예부터 물김치나 겉절이 무침, 돌나무 김치로 많이 이용되어온 돌나물의 암세포 증식억제 및 암예방 효과를 검색하고 나아가 도라지 추출물과의 암세포 증식억제 상승효과를 보기 위하여 실시하였다. 돌나물의 암세포 증식억제 효과를 MTT assay로 실험한 결과, 3종의 암세포주(HepG2, HeLa, MCF-7) 모두 돌나물의 ethylether 분획층(SSMEE)에서 아주 높은 암세포 증식억제 효과를 보였으며, ethylacetate 분획층(SSMEA)에서도 유의적인 암세포 증식억제 효과를 나타내었다. 또한, 돌나물 분획물의 암예방 QR유도 활성을 HepG2 세포주를 이용하여 실험한 결과, 다른 분획층에 비해 비극성 용매층인 ethylether 분획층(SSMEE)과 hexane 분획층(SSMH)에서 유의적으로 QR유도 활성을 증가시키는 것으로 나타났다. 한편, 돌나물과 도라지와의 일정비 조합을 통해 상승효과를 본 결과, $IC_{50}$/이 되는 도라지의 butanol층 (PGMB)dfm 일정량 첨가했을 때 용매별 돌나물의 분획층 모두에서 암세포 증식억제를 상승시키는 효과를 나타내었고, 암예방 QR 유도활성 효과도 훨씬 상승하였으므로, 돌나물 조리시 유사한 부재료를 사용하는 도라지의 성분을 일정량 첨가하여 겉절이 무침이나 김치로 이용될 때 돌나물 성분의 생리활성 효과가 더욱 상승될 것으로 사료되며, 이후 돌나물의 생리활성 물질 구조 및 기전 규명에 유익한 자료가 될 것으로 사료된다.