• Toxicological Research
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• 제28권1호
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• pp.33-38
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• 2012

In this study, we investigated the effect of methanolic extract isolated from the root of Lycoris aurea (LA) on the growth of cancer cells and the tube formation activity of endothelial cells. Various cancer cells were treated with LA at doses of 0.3, 1, 3, 10 or 30 ${\mu}g/ml$ and LA significantly suppressed the growth of several cancer cell lines, including ACHN, HCT-15, K-562, MCF-7, PC-3 and SK-OV-3, in a dose-dependent manner. We also found that LA induced cell cycle arrest at G2/M phase in ACHN renal cell adenocarcinoma cells. Further study demonstrated that LA concentration-dependently inhibited the tube formation, which is a widely used in vitro model of reorganization stage of angiogenesis, in human umbilical vein endothelial cells. Collectively, these results show that LA inhibits the growth of cancer cells and tube formation of endothelial cells and the growth-inhibitory effect of LA might be mediated, at least in part, by blocking cell cycle progression.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.322-327
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• 2018

A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6047-6053
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• 2012

Bracken fern [Pteridium aquilinem (L.) kuhn (Dennstaedtiaceae)] is one of the most common species on the planet. It has been consumed by humans and animals for centuries. Use by some human groups is because they believe bracken fern is good for health as plant medicine. However, it is also one of the few known plants that can cause tumors in farm animals. Many interested groups have focused their attention on bracken fern because of these interesting features. In order to evaluate the biological effects of exposure to this plant in cellular level, human cancer cell lines were treated with the fern dichloromethane extracts and the genotoxic and cytotoxic effects were studied. Anti-proliferative/cytotoxic effects were evaluated by cell count, MTT assay and flow cytometry methods with three different cancer cell lines, TCC, NTERA2, and MCF-7, and two normal cells, HDF1 and HFF3. Pro-apoptotic effects of the extracts were determined by DAPI staining and comet assay, on TCC cancer cells compared to the normal control cell lines. Cellular morphology was examined by light microscopy. Our present study showed that the extract caused DNA damage and apoptosis at high concentrations ($200{\mu}g/mL$) and also it may induce cell cycle arrest (G2/M phase) at mild concentrations (50 and $30{\mu}g/mL$) depending on the cell type and tumor origin. These results indicate that bracken fern extract is a potent source of anticancer compounds that could be utilized pharmaceutically.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6869-6874
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• 2013

Background: Vascular endothelial growth factor and matrix metalloproteinases are two important factors for angiogenesis associated with breast cancer growth and progression. The present study was aimed to examine the effects of tamoxifen and tranilast drugs singly or in combination on proliferation of breast cancer cells and also to evaluate VEGF and MMP-9 expression and VEGF secretion levels. Materials and Methods: Human breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with tamoxifen and/or tranilast alone or in combination and percentage cell survival and proliferative activity were evaluated using LDH leakage and MTT assays. mRNA expression and protein levels were examined by real-time RT-PCR and ELISA assay, respectively. Results: LDH and MTT assays showed that the combined treatment of tamoxifen and tranilast resulted in a significant decrease in cell viability and cell proliferation compared with tamoxifen or tranilast treatment alone, with significant decrease in VEGF mRNA and protein levels. We also found that tamoxifen as a single agent rarely increased MMP-9 expression. A decrease in MMP-9 expression was seen after treatment with tranilast alone and in the combined treatment MMP-9 mRNA level was decreased. Conclusions: This combination treatment can able to inhibit growth, proliferation and angiogenesis of breast cancer cells.

• 생약학회지
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• 제45권2호
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• pp.174-180
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• 2014

D-Pinitol, an anti-diabetic substance, is a naturally occurring compound found in legumes. In this study, we investigated the inhibitory effect of D-pinitol on growth and recurrence of breast cancer. When D-pinitol was treated on MDA-MB-231 or MCF-7 breast cancer cells, it was observed that the viability of the two cancer cell lines was reduced in MTT assay. In order to examine the effect on the growth of breast tumor, mouse xenograft assay was carried out. On day 0, nine millions cells of MDA-MB-231 were injected subcutaneously into nude mouse and D-pinitol was administered orally at the dose of 500 mg/kg or 1000 mg/kg body weight for consecutive 45 days. Tumor size was reduced in dose-dependent manner upto 95.4% in 1000 mpk-treated group, compared with the non-treated control group. When D-pinitol was co-administrated with $4{\mu}g$ of doxorubicin, recurrence of breast tumor was delayed by two weeks, compared with the mouse group of doxorubicin monotherapy. Consistent with this data, it was observed that the population of cancer stem cells (CSCs), responsible for recurrence of cancer, within tumor mass was significantly reduced. Taken together, D-pinitol inhibits the growth of breast cancer and relapse of the tumor by suppressing the proliferation of CSCs.

• 한국식품영양학회지
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• 제25권3호
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• pp.447-453
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• 2012

Various types of tea are consumed as a popular beverage worldwide particularly in Asian countries such as Korea, China, and Japan. The purpose of this study was to investigate the mineral contents, antioxidant properties and anticancer activity of Yak-Sun tea that is prepared by six oriental medicinal herbs. The results of the mineral contents were as follows; Ca, Mg, and Na contents were higher than those of green tea, whereas Fe, P, and K contents were lower than those of green tea. The total phenolics and flavonoid content of the Yak-Sun tea were higher than those of green and black teas. The $IC_{50}$ values of DPPH radical, hydroxyl radical, hydrogen peroxide radical scavenging of Yak-Sun tea were 0.78, 1.58, and 2.04 $mg/m{\ell}$, respectively, whereas the radical scavenging values of ${\alpha}$-tocopherol was 0.06, 0.05, and 0.09 $mg/m{\ell}$, respectively. When cancer cells were treated with Yak-Sun tea, the anticancer activity increased in a dose dependent manner. HCT116 colon cancer cell lines were dramatically increased, as compared to other cancer cell lines, such as MCF-7, H460, and MKN45 cell lines. The results of this study demonstrated that Yak-Sun tea could function as a tea to enhance health conditions for antioxidant and anticancer activity.

• 한국식품영양학회지
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• 제26권4호
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• pp.609-614
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• 2013

본 연구는 도꼬마리의 뿌리와 열매 부위별 항산화 활성의 검증을 통해 유효 생리활성 성분이 많은 부위를 탐색하고자 뿌리와 열매를 메탄올로 추출하여 항산화 활성물질, 라디칼 소거능, in vitro에서 항암 활성을 측정하였다. 항산화 물질인 폴리페놀과 플라보노이드 함량은 뿌리보다는 열매 부위에 6배 가량 높은 함량이 나타났다. ABTS, DPPH, Hydroxyl radical 소거능을 측정한 결과, 뿌리에서 $IC_{50}$% 6.02, 1.29, 3.88mg/ml이며, 열매에서는 0.81, 0.16, 0.44mg/ml로 열매에서 소거능이 높게 나타났다. 항암 활성을 알아보기 위하여 유방암세포(MCF-7), 위암세포(AGS), 폐암세포(A-549), 인체대장암세포(HCT-116), 간암세(Hep-G2) 및 전립선암(PC-3)에 처리하여 암세포 성장 억제 정도를 확인한 결과, 도꼬마리 열매와 뿌리 부위에 0.5mg/ml 농도에서 각각 26%, 36% 전립선 암세포 성장 억제 정도를 확인할 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.257-261
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• 2016

Cancer causes cells to avoid death while being the second cause of death in the world itself. Damaged cells in the absence of apoptosis will increasingly amplify their inefficient genome. Of the two main apoptosis inducing pathways in cells, the first has p53 protein as the main initiating factor in the cascade. According to research results this protein s mutated in 50% of cancers and sointerest has cooncentrated on the second pathway that features death receptors. Among these receptors TRAIL1/DR5 is especially expressed in cancer cells. So targeting such receptors can initiate the apoptotic cascade in cells. Interestingly by substitution of activating ligands with antibodies as agonists, we could efficiently turn on the apoptosis pathway. First of all, three small peptides from the DR5 protein extracellular domain were synthesized and injected with two different kind of adjuvants (Fround and liposomal encapsulation) separately into mice at 15 day intervals. As a result, liposomal peptides induced the immune system more efficient than Frounds adjuvant and at the end point the antibodies which were obtained from liposomal peptide injection induced much more effective death. Liposomal formol could be used as an adjuvant in immunization utilizing small peptides. They carry, protect and deliver peptides very efficiently. In addition, small peptides of a certain size from the extracellular domain of DR5 proteins not only can induce immune system but also produce antibodies playing a remarkable anti-cancer roles against breast cancer cells (MCF-7).

• BMB Reports
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• 제31권6호
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• pp.565-571
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• 1998

The expression of the endogenous human apolipoprotein(apo)E gene was significantly induced when HepG2 cells were treated with exogenous 25-hydroxy-cholesterol. This sterol-mediated apoE gene upregulation appears to require the participation of a positive element for the apoE gene transcription (PET) ( -169/ -140), a core sequence of upstream regulatory element (URE)1 enhancer of the human apoE gene. This PET was renamed as sterol regulatory element (SRE)4 based on its new role as a sensor for the level of intracellular sterol. Furthermore, a gel mobility shift analysis showed that binding activity of the SRE4 binding protein (BP) obtained from HepG2 cells was induced by sterol treatment, while that from either MCF7 or BT20 cells remained unchanged. Binding activity of SRE4BP was also induced in mouse macrophage cells, J774A.1, by sterol treatment, but it was drastically reduced when cells were subjected to treatment of AY-9944, a potent inhibitor for sterol synthesis. However, binding activity of Spl, which is a co-binding protein to the SRE4 region, remained the same in either condition, suggesting that SRE4BP (formally known as PETBP) may be mainly responsible for the sterol-mediated regulation of the apoE gene expression. Deletion analysis of the core binding site of SRE4BP by gel mobility shift assays showed that the minimal sequence of the SRE4BP binding appears to reside between -157 and -140, confirming the identity of SRE4 with the previously determined core sequence of URE1.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5131-5136
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• 2012

Cancer is one of the major health problems worldwide and its current treatments have a number of undesired adverse side effects. Natural compounds may reduce these. Currently, a few plant products are being used to treat cancer. In this study, goniothalamin, a natural occurring styryl-lactone extracted from Goniothalamus macrophyllus, was investigated for cytotoxic properties against cervical cancer (HeLa), breast carcinoma (MCF-7) and colon cancer (HT29) cells as well as normal mouse fibroblast (3T3) using MTT assay. Fluorescence microscopy showed that GTN is able to induce apoptosis in HeLa cells in a time dependent manner. Flow cytometry further revealed HeLa cells treated with GTN to be arrested in the S phase. Phosphatidyl serine properties present during apoptosis enable early detection of the apoptosis in the cells. Using annexin V/PI double staining it could be shown that GTN induces early apoptosis on HeLa cells after 24, 48 and 72 h. It could be concluded that goniothalamin showing a promising cytotoxicity effect against several cancer cell lines including cervical cancer cells (HeLa) with apoptosis as the mode of cell death induced on HeLa cells by Goniothalamin was.