• BMB Reports
• /
• v.36 no.3
• /
• pp.269-274
• /
• 2003

In the fight against cancer, novel chemotherapeutic agents are constantly being sought to complement existing drugs. Various studies have presented evidence that the apoptosis that is induced by these anticancer agents is implicated in tumor regression, and Bcl-2 family genes play a part in apoptosis following treatment with various stimuli. Here, we present data that a styrylpyrone derivative (SPD) that is extracted from the plant Goniothalamus sp. showed cytotoxic effects on the human breast cancer cell line MCF-7. SPD significantly increased apoptosis in MCF-7 cells, as visualized by phase contrast microscopy and evaluated by the Tdt-mediated dUTP nick end-labeling assay and nuclear morphology. Western blotting and immunostaining revealed up-regulation of the proapoptotic Bax protein expression. SPD, however, did not affect the expression of the anti-apoptotic protein, Bcl-2. These results, therefore, suggest SPD as a potent cytotoxic agent on MCF-7 cells by inducing apoptosis through the modulation of Bax levels.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.10
• /
• pp.5687-5692
• /
• 2013

Type 2 diabetes mellitus (T2DM) has contributed to advanced breast cancer development over the past decades. However, the mechanism underlying this contribution is poorly understood. In this study, we determined that high glucose enhanced proteasome activity was accompanied by enhanced proliferation, migration and invasion, as well as suppressed apoptosis, in human breast cancer MCF-7 cells. Proteasome inhibitor bortezomib (BZM) pretreatment mitigated high glucose-induced MCF-7 cell growth and invasion. Furthermore, high glucose increased protein kinase C delta ($PKC{\delta}$)-phosphorylation. Administration of the specific $PKC{\delta}$ inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth and invasion. In addition, $PKC{\delta}$ inhibition by both rottlerin and $PKC{\delta}$ shRNA significantly suppressed high glucose-induced proteasome activity. Our results suggest that $PKC{\delta}$-dependent ubiquitin proteasome system activation plays an important role in high glucose-induced breast cancer cell growth and metastasis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.10
• /
• pp.5805-5810
• /
• 2013

This study was conducted to analyze the molecular mechanisms responsible for anti-proliferation effects of glaucocalyxin A in cultured MCF-7 and Hs578T breast cancer cells. The concentration that reduced cell viability to 50% (IC50) after 72 h treatment was derived and potential molecular mechanisms of anti-proliferation using the IC50 were investigated as changes in cell cycle arrest and apoptosis. Gene and protein expression changes related to apoptosis were investigated by semi-quantitative RT-PCR and western blotting, respectively. Involvement of phosphorylated mitogen-activated protein kinases and JNK signaling in regulation of these molecules was characterized by western blotting. Cell viability decreased in a concentration-dependent manner and the IC50 was determined as $1{\mu}M$ in MCF-7 and $4{\mu}M$ in Hs578T cell. Subsequently, we demonstrated that the GLA-induced MCF-7 and Hst578T cell death was due to cell cycle arrest at the G2/M transition and was associated with activation of the c-jun N-terminal kinase (JNK) pathway. We conclude that GLA has the potential to inhibit the proliferation of human breast cancer cells through the JNK pathway and suggest its application forthe effective therapy for patients with breast cancer.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.20 no.3
• /
• pp.35-44
• /
• 2007

Purpose: This study was conducted to investigate the anti-proliferative effects of Ulmi Pumilae Cortex Extracts(UPCE) on MCF-7(human, breast, adenocaecinoma) and NIH3T3 (human, murine, fibroblast). Methods: MCF-7 cells and NIH3T3 cells were cultured and seeded in cell culture plates, respectively. UPC was extracted with hot water and then further fractionated it into five types: hexane, chloroform, ethyl acetate, butanol, and water soluable fractions. These five different fractions from UPCE were tested for their anti-proliferative effects on MCF-7 cells and NIH3T3 cells by MMT assay. Results: Among the five solvent-fractions of UPCE, n-hexane fraction and ethyl acetate fraction showed a strong anti-proliferative effects on MCF-7 cells but they displayed significant cytotoxicity on NIH3T3 cells, too. On the other hand, chloroform fraction showed a marked anti-proliferative effects on MCF-7 cells and low cytotoxicity on NIH3T3 cells. Conclusion: Chloloform fraction from UPCE showed selective anti-cancer activities on human breast cancer cell MCF-7 relatively to the other fractions.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.24 no.3
• /
• pp.385-389
• /
• 2010

Butein(3,4,2',4-tetrahydroxychalcone) has been reported anticancer effects in several cancer type, which is prostate, bladder cancer but breast cancer is not. This study was to investigate the antiproliferative effects by butein(3,4,2',4-tetrahydroxychalcone) in MCF-7 human breast carcinoma cells. We invastigated the effects of dose-dependently cell growth inhibition by butein, which could be proved by WST-1 assay. Also, flow cytometry analysis was butein increase percentage of subG1 phase. As well as, butein induces apoptosis through the expression of caspase-8,-3 and poly(ADP-ribose) polymerase(PARP) activation but not in DMSO treated cells. Taken together, this results suggest that butein induced MCF-7 apoptosis through extrinsic pathway and thus may have potential tumor suppressor in breast cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.2
• /
• pp.643-646
• /
• 2014

Objective: This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness. Methods: Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined. Results: TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR-2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells. Conclusion: TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.12
• /
• pp.5001-5007
• /
• 2014

The acetyltransferase inhibitor garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Anti-cancer activity has been suggested but there is no report on its action via inhibiting acetylation against cell proliferation, cell cycle progression, and apoptosis-inhibtion induced by estradiol ($E_2$) in human breast cancer MCF-7 cells. The main purposes of this study were to investigate the effects of the acetyltransferase inhibitor garcinol on cell proliferation, cell cycle progression and apoptosis inhibition in human breast cancer MCF-7 cells treated with estrogen, and to explore the significance of changes in acetylation levels in this process. We used a variety of techniques such as CCK-8 analysis of cell proliferation, FCM analysis of cell cycling and apoptosis, immunofluorescence analysis of NF-${\kappa}B$/p65 localization, and RT-PCR and Western blotting analysis of ac-H3, ac-H4, ac-p65, cyclin D1, Bcl-2 and Bcl-xl. We found that on treatment with garcinol in MCF-7 cells, $E_2$-induced proliferation was inhibited, cell cycle progression was arrested at G0/G1 phase, and the cell apoptosis rate was increased. Expression of ac-H3, ac-H4 and NF-${\kappa}B$/ac-p65 proteins in $E_2$-treated MCF-7 cells was increased, this being inhibited by garcinol but not ac-H4.The nuclear translocation of NF-${\kappa}B$/p65 in $E_2$-treated MCF-7 cells was also inhibited, along with cyclin D1, Bcl-2 and Bcl-xl in mRNA and protein expression levels. These results suggest that the effect of $E_2$ on promoting proliferation and inhibiting apoptosis is linked to hyperacetylation levels of histones and nonhistone NF-${\kappa}B$/p65 in MCF-7 cells. The acetyltransferase inhibitor garcinol plays an inhibitive role in MCF-7 cell proliferation promoted by $E_2$. Mechanisms are probably associated with decreasing ac-p65 protein expression level in the NF-${\kappa}B$ pathway, thus down-regulating the expression of cyclin D1, Bcl-2 and Bcl-xl.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.05a
• /
• pp.91-91
• /
• 2002

We have examine the effect of all trans retinoic acid and 9-cis-retinoic acid on human breast cancer cell proliferation using SRB assay and cell cycle analysis. 1)In MCF-7 cells, in the presence of phenol red, either all trans retinoic acid or 9-cis-retinoic acid treatment showed the inhibition of the cell proliferation over control cells and also inhibit the estrogen stimulated cell proliferation when it was given together with estrogen.(omitted)

• Korean Journal of Clinical Laboratory Science
• /
• v.56 no.1
• /
• pp.73-84
• /
• 2024

A pulsed electromagnetic field (PEMF) enhances the efficacy of several anticancer drugs. Doxorubicin (DOX) is an anticancer agent used to treat various malignancies, including breast cancer. This study examined whether a PEMF increases the anticancer effect of DOX on MCF-7 human breast cancer cells and elucidated the underlying mechanisms affected by PEMF stimulation in DOX-treated MCF-7 human breast cancer cells. A cotreatment with DOX and a PEMF potentiated the reduction in MCF-7 cell viability compared to the treatment with DOX alone. The PEMF elevated DOX-induced G1 arrest by affecting cyclin-dependent kinase 2 phosphorylation and the expression of G1 arrest-related molecules, including p53, p21, cyclin E2, and polo like kinase 1. In addition, PEMF increased the DOX-induced upregulation of proapoptotic proteins, such as Fas and Bcl-2-associated X, and the downregulation of antiapoptotic proteins, including myeloid leukemia 1 and survivin. PEMF promoted the DOX-induced activation of caspases-8, -9, and -7 and poly (adenosine diphosphate-ribose) polymerase cleavage in MCF-7 cells. In conclusion, PEMF enhances the anticancer activity in DOX-treated MCF-7 breast cancer cells by increasing G1 cell cycle arrest and caspase-dependent apoptosis. These findings highlight the potential use of a PEMF as an adjuvant treatment for DOX-based chemotherapy against breast cancer.

• Environmental Mutagens and Carcinogens
• /
• v.26 no.1
• /
• pp.12-19
• /
• 2006

Cadmium, a human carcinogen, can induce toxicity in various cell lines and organs. Despite extensive research, the mechanisms of cadmium-induced cell toxicity and estrogenic potential in human are not clear. This study was performed to investigate cadmium-induced toxicity on human breast cancer cells: MCF-7 cells, an estrogen receptor (ER) positive breast cancer cells, and MDA-MB-231 cells, an ER negative breast cancer cells. MCF-7 cells was proved to be more sensitive than the other cell lines (IC50 = $50\;{\mu}M$ at MCF-7 cells and $120{\mu}M$ at MDA-MB-231). The expression of JNK and AP-1 transcription factors such as c-Jun and c-Fos dependent transcription were increased by cadmium treatment. Inhibition of ER activation by ER antagonist (tamoxifen or ICI 182,780) significantly recovered the viablity and inhibited apoptotic cell death. This suggested that cadmium-induced cell death in ER (+) cells was mediated by JNK/AP-1 pathway and this pathway was more stimulated by ER activated by cadmium. Co-treatment of antioxidants such as selenium (Se), butylated hydroxyanisole (BHA), glutathione (GSH), or N-acetyl-L-cysteine (NAC) recovered the cadmium-induced cell death in MCF-7 cells. Cadmium-induced lipid peroxidation was decreased by GSH, NAC, or BHA in MCF-7 cells. The expression of SOD protein was decreased by cadmium ($100{\mu}M$) but recovered by GSH, NAC, BHA, or Se. Our data showed that the cadmium-induced cell toxicity in human breast cancer cells could be protected by the antioxidants (Se, BHA, NAC, GSH, or NAC) and ER antagonist (tamoxifen or ICI 182,780). Therefore, toxicity of cadmium in breast cancer were mediated by oxidative stress and $ER{\alpha}$.