• Asian Pacific Journal of Cancer Prevention
• /
• 제15권1호
• /
• pp.273-276
• /
• 2014

Ellagic acid has been shown to inhibit tumor cell growth. However, the underlying molecular mechanisms remain elusive. In this study, our aim was to investigate whether ellagic acid inhibits the proliferation of MCF-7 human breast cancer cells via regulation of the TGF-${\beta}$/Smad3 signaling pathway. MCF-7 breast cancer cells were transfected with pEGFP-C3 or pEGFP-C3/Smad3 plasmids, and treated with ellagic acid alone or in combination with SIS3, a specific inhibitor of Smad3 phosphorylation. Cell proliferation was assessed by MTT assay and the cell cycle was detected by flow cytometry. Moreover, gene expression was detected by RT-PCR, real-time PCR and Western blot analysis. The MTT assay showed that SIS3 attenuated the inhibitory activity of ellagic acid on the proliferation of MCF-7 cells. Flow cytometry revealed that ellagic acid induced G0/G1 cell cycle arrest which was mitigated by SIS3. Moreover, SIS3 reversed the effects of ellagic acid on the expression of downstream targets of the TGF-${\beta}$/Smad3 pathway. In conclusion, ellagic acid leads to decreased phosphorylation of RB proteins mainly through modulation of the TGF-${\beta}$/Smad3 pathway, and thereby inhibits the proliferation of MCF-7 breast cancer cells.

• 생명과학회지
• /
• 제19권2호
• /
• pp.157-162
• /
• 2009

Nitric oxide (NO)는 세포 안의 다양한 생리학적, 병리학적 조건에서 확산, 세포 간 messenger와 같은 다양한 기능이 있으며, NO는 암세포나 macrophage 등과 같은 세포에서는 apoptosis를 유도하고, 정상세포나 내피 세포에서는 apoptosis를 억제한다고 보고되어져 있다. NO가 유방암 세포주인 MCF-7 세포에서는 apoptosis를 유도하는지 확인하기 위해 NO donor인 SIN-1을 처리하였다. SIN-1은 48시간 처리 시에도 세포 생존율에 영향을 주지 않았고, 세포주기나 성장 패턴에도 아무런 변화를 주지 않았다. 그러나 p53의 발현은 SIN-1 처리 시간에 따라 증가하였고, bcl-2, MDM2, p21의 발현도 함께 증가하였다. Bax의 발현은 SIN-1 처리 시에 변화가 없었다. MCF-7 세포에서 NO에 의한 apoptosis 억제를 보기 위하여, SIN-1을 선처리한 세포에 $CoCl_2$를 처리하였다. 세포에 $CoCl_2$ 만을 처리한 군에서는 확연한 apoptosis를 나타내었지만, SIN-1을 24 시간 선처리한 세포에서는 apoptosis를 관찰할 수 없었다. Cobalt Chloride에 의해 감소되었던 p53, MDM2, bcl-2 발현 역시 SIN-1을 24시간 선처리한 세포에서 증가하였다. 이런 결과들은 SIN-1에 의해 발현된 MDM2가 p53의 기능을 막으며, 또한 p21과 bcl-2의 발현이 유도되어 apoptosis를 억제함을 제시한다.

• Preventive Nutrition and Food Science
• /
• 제3권2호
• /
• pp.163-168
• /
• 1998

Inhibitory effect of indole oligomers induced from indole-3-carbinol(I3C) on the growth of breast cancer cells was studied. We gernerated the reaction mixtures (RXM) at ambient temperature by treating a stirred aqueous solution of I3C (typeically 0.25ml) at a concentration of 12 $\mu$mol/ml) with hydrochloric acid (typically 28$\mu$l of a 1 mmol/ml solution). RXM was fractionated by the column chromatography. The fractions with similar UV-pattern were further fractionated by HPLC and 3.3'-diindoylmethane (DIM) and other indole oligomers were identified. I3C, RXM, and it derived indole compounds were added to MCF-7 cells and cultured in the presence of 10-7M estradiol for 7 days. the growth-inhibitory effect of I3C and DIM on the growth of MCF-7 cell was very strong. The synthetic DIM also revealed antiproliferative effect on MCF-7 cel. The fractions containing high DIM content (77%), were most effective in inhibiting MCF-7 cell growth induced by estradiol. With these results, we suggest that I3C and DIM might have anticarcinogenic effect on the breast cancer.

• Advances in Traditional Medicine
• /
• 제6권4호
• /
• pp.286-292
• /
• 2006

In this study, we evaluated the antiproliferative effects of Panax notoginseng, ginsenoside Rb1, and notoginsenoside R1 in the human breast carcinoma MCF-7 cell line. Our results indicated that both Panax notoginseng radix extract (NRE) and Panax notoginseng rhizoma extract (NRhE) possess significant antiproliferative activities in MCF-7 cells. Compared to control group (100%), at the concentrations of 0.05, 0.5, and 1.0 mg/ml NRE, cell growth was concentration-dependently reduced to 81.0 ${\pm}$ 6.1 (P < 0.01), 34.2 ${\pm}$ 4.8 (P < 0.001), and 19.3 ${\pm}$ 1.9 (P < 0.001), respectively. Similar results with NRhE at concentrations of 0.5 and 1.0 mg/ml were obtained in these MCF-7 cells. To identify the responsible chemical constituent, we tested the antiproliferation effects of two representative saponins, ginsenoside Rb1 and notoginsenoside R1, on the MCF-7 cells. The data showed that ginsenoside Rb1 was endowed with antiproliferative properties, while notoginsenoside R1 did not have an inhibitory effect in the concentrations tested. Our studies provided evidence that Panax notoginseng extracts and ginsenoside Rb1 may be beneficial, as adjuvants, in the treatment of human breast carcinoma.

• Journal of Acupuncture Research
• /
• 제20권3호
• /
• pp.45-62
• /
• 2003

Objective : To examine the effects of Beevenom on the cell proliferation of human breast carcinoma cell line MCF-7, we performed various experiments such as does-dependent effect of Beevenom on cell proliferation and viability, morphological changes, and alterations of apoptosis/cell cycle-regulatory gene products. Methods : Beevenom induced cell viability and proliferation of MCF-7 cells in a concentration-dependent manner. The anti-proliferative effect by Beevenom treatment in MCF-7 cells was associated with morphological changes such as membrance shrinking and cell rounding up. Results : Beevenom induced apoptotic cell death in a concentration-dependent manager, which was associated with degradation of ${\beta}$-catenin, an apoptotic target protein. Beevenom induced the Bax expressions, a pro-apoptotic gene, both in protein and mRNA levels, however, the levels of Bcl-$X_{S/L}$ expression, an anti-apoptotic gene, were down-regulated in Beevenom-treated cells. Western blot analysis and RT-PCT data revealed that the levels of cyclin of B1 protein and cyclin E mRNA were reduced by Beevenom treatment in MCF-7 cells, respectively, where as the expression of tumor suppressor p53 and cyclin dependent kinase inhibitor p21 mRNA were markedly increased in a concentration-dependent fashion. Conclusions : Taken together, these findings suggest that Beevenom induced inhibition of human breast cancer cell proliferation is associated with the induction of apoptotic cell death and Beevenom may have therapeutic potential in human breast cancer.

• 대한임상검사과학회지
• /
• 제56권1호
• /
• pp.73-84
• /
• 2024

펄스 전자기장(pulsed electromagnetic field, PEMF)은 여러 항암제의 항암 효과를 향상시키는 것으로 알려져 있고 독소루비신(doxorubicin, DOX)은 유방암을 포함한 다양한 종류의 악성 종양을 치료하는 데 사용되는 항암제이다. 본 연구는 PEMF가 MCF-7 유방암 세포에 대한 DOX의 항암 효과 증진 여부를 조사하고 관련기전을 규명하기 위해 진행되었다. 본 연구팀은 DOX와 PEMF를 동시에 처리하면 DOX 단독 처리에 비해 MCF-7 유방암 세포의 생존율 감소가 더 커지는 것을 확인하였다. PEMF는 cyclin-dependent kinase 2의 인산화와 p53, p21, 사이클린 E2 및 polo like kinase 1의 단백질 발현에 영향을 주어 DOX 처리에 의한 G1 세포주기 정지를 더욱 증가시켰다. 또한, PEMF는 DOX 처리에 의한 Fas와 Bcl-2-associated X의 증가, myeloid leukemia 1과 survivin의 감소, 카스파제(caspase)-8/9/7의 활성 및 poly (adenosine diphosphate-ribose) polymerase 절단을 더욱 증가시켰다. 이러한 연구결과를 바탕으로, 본 연구팀은 PEMF는 DOX 처리에 의한 G1 세포주기 정지와 카스파제 의존적 세포자멸사를 더욱 증가시켜 DOX 처리에 의한 MCF-7 세포의 생존율 감소를 더욱 증진시킴을 확인할 수 있었다.

• Radiation Oncology Journal
• /
• 제22권2호
• /
• pp.145-154
• /
• 2004

목적 : 인체 유방암 세포주인 MCF극에 새로운 CDCA합성유도체인 HS-1200을 방사선과 함께 처치하여 아포토시스 유도 활성 및 방사선 감작 효과를 관찰하고자 하였다. 대상 및 방법 : MCF-7 세포에 2$\~$8 Gy의 X-ray와 16$\mu$M 농도의 HS-1200을 처리한 세포들의 세포 생존 곡선을 clonogenic assay를 통하여 구하였다. 아포토시스 유도 확인은 8 Gy의 X-ray와 40$\mu$M 농도의 HS-1200을 전 처치하여 구한 agarose gel 전기영동 및 Hoechst staining을 이용하였다. 면역형광법을 이용한 cytochrome c, Bax 및 AIF들의 관찰과 미토콘드리아 막전위 측정을 시행하였다 Western blotting을 통한 PARP (poly (ADP-ribose) poly-merase) cleavage, Bax, Bcl-2, Bak 및 AIF 들의 발현을 관찰하였다. 결과 : 2$\~$8 Gy의 X-ray를 조사한 군(R)과 HS-1200 처리 후 2$\~$8 Gy의 X-ray를 조사 한 군(HR)의 세포 생존 곡선을 비교하니 HR군에서 세포 감작 효과를 관찰할 수 있었다. DNA ladder는 R군에서는 72시간재 관찰되는 반면에 HR 군에서는 24시간째 관찰되어 DNA 분절이 빠르게 진행됨을 알 수 있었고, PARP cleavage의 관찰에서도 R 군에 비해 24시간 빠르게 진행되었다. 면역 형광법을 이용한 실험에서도HR군이 R 근에 비하여 미토콘드리아 막전위($\Delta$$\psi$$_{m}$)의 급격한 감소, cytochrome의 다량 방출, Bax의 증가된 점상 변화 등이 관찰되었고, AIF의 변화는 뚜렷하지 않았다. Western blotting을 이용한 Bax, Bcl-2, Bak 및 AIF들의 발현을 관찰하였을 때 Bax 만 HR 군에서 시간대별로 증가되는 추세를 보인 반면 Bcl-2, Bak 및 AIF들의 발현은 특이한 차이를 발견할 수 없었다. 결론 : 인체 유방암 세포주(MCF-7)에서 새로운 담즙산 합성 유도체인 HS-1200은 방사선 조사에 의한 아포토시스의 유도를 감작시키는 사실을 관찰하였다. 아포토시스 유도감작 증가는 Bax/Bcl-2 분율의 상대적 증가로 기인한다고 생각한다. 상기 결과를 토대로 HS-1200의 항암 치료제로서의 역할에 관한 기초 자료로서의 유용성을 제시할 수 있었다.

• 대한의생명과학회지
• /
• 제23권3호
• /
• pp.290-294
• /
• 2017

Metformin or sodium salicylate is known to induce apoptosis and G0/G1 phase arrest in a variety of cancer cells. However, the anti-cancer effects of the combined treatments for these drugs-induced apoptosis are yet unclear. Here, we found that the combined treatment of metformin and sodium salicylate increased the efficacy of chemotherapeutics against breast cancer cells. These combined drugs significantly inhibited cellular proliferation and induced apoptosis at an earlier stage in human MCF-7 breast cancer cells. Also, co-treatments of metformin and sodium salicylate induced G1 cell cycle arrest in MCF-7 cells more effectively than either agent alone. Taken together, these results demonstrate that dual metformin/sodium salicylate treatment prevents proliferation of MCF-7 cells by inducing apoptosis and G1 cell cycle arrest.

• Journal of Life Science
• /
• 제9권1호
• /
• pp.40-44
• /
• 1999

Glutathione S-transferase (GST) is a multifunctional protein that catalyzes the catalyzes the conjugation of glutathione with electrophilic compounds. It exists in a variety of isoenzy-matic froms with a wide range of substrate specificity and plays a pivotal role in detoxification of various drugs. In order to elucidate the GST-${\pi}$'s involvement of multidrug resistance (MDR) in drug-resistant tumor cell lines, we determined GST-${\pi}$ content by "1 step sandwich method". Consequently, adriamycin resistant cells of MCF-7 (MCF-7/ADM) have 7-fold increase of GST-${\pi}$ content than that of MCF-7 cells, while its {TEX}$IC_{50}${/TEX} was 116-fold greater than parent cell line. By northrn blotting, we compared whether MCF-7/ADM cells express GST-${\pi}$ mRNA. The GST-${\pi}$ mRNA expression in these cells was not inducible, but constitutive when treated for 24 h with a concentration of 0, 20, 200, and 2000 nM of adriamycin, respectively. Taken together, these results suggest that GST-${\pi}$ may not be directly associated with multidrug resistance in these human cancer cell lines.ell lines.

• Molecular & Cellular Toxicology
• /
• 제2권1호
• /
• pp.15-20
• /
• 2006

Genistein is a potent, plant-derived isoflavone that displays estrogenic activity at low concentrations but inhibits proliferation at high amounts. However, the molecular mechanism of genistein is not completely understood. In the present study, the biphasic effects (estrogenic and antiestrogenic activity) of genistein on the growth of MCF-7 cells were identified. Genistein within a low range of concentration, $1-10\;{\mu}M$, stimulated proliferation, while $50-100\;{\mu}M$ caused apoptotic cell death. Additionally, genistein at a low concentration induced estrogen receptor (ER)-mediated gene expression and ER phosphorylation. When pre-treated with PD98059, an MEK inhibitor, ER-mediated gene expression and ER phosphorylation by genistein were noticeably increased. However, the increased gene expression and phosphorylation did not enhance cell proliferation. Moreover, it was observed that ER-mediated signaling performs an important role in the MAPK pathway. The proliferation and apoptosis in genistein-treated MCF-7 cells were partially dependent on the Bcl-2 level. The addition of IC1 182, 780, an estrogen receptor antagonist, inhibited Bcl-2 expression induced by genistein. This study suggests that there is a close relationship between Bcl-2 and the ER signaling pathways in MCF-7 cells.