• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.105-105
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• 2001

In an attempt to provide useful information on the development of an artifitial nerve tubing, proliferative and migrative properties of two glioma cell lines, C6 rat glioma cells and Hs683 human glioma cells, were examined. The present study shows that C6 cells proliferated more rapidly than Hs683 cells. The Hs683 cells are more adequate for the development of nerve tubing since unlike C6 cells, they are of human origin and known to be non-tumorigenic. In order to enhance proliferative and migrative abilities of Hs683 cells for the application as an artificial nerve tubing, we studied the effect of glial cell-derived neurotrophic factor (GDNF) on Hs683 cells. Cells were seeded in the scaffolds (polymer constructs), fabricated with type I collegen and alginate modified with cinnamoyl moiety, in the presence or absence of GDNF Stimulatory effect of GDNF on the proliferation and migration of Hs683 cells cultured in the scaffolds is currently under investigation. In addition, possible neuroprotective activities of natural products which inhibit staurosporine-induced apoptosis of glioma cells are also being studied.

• 한국축산식품학회지
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• 제38권6호
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• pp.1168-1178
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• 2018

The present study aimed to characterise anti-oxidant peptides from water-soluble protein extracts of Hanwoo beef and evaluate their anti-proliferative effect on human colorectal carcinoma cells (HCT116). Antioxidant peptides were purified from the low-molecular-weight fraction (<3 kDa) of Hanwoo beef extract. Antioxidant activity of peptide fractions was determined using the oxygen radical absorbance capacity (ORAC) assay. Purified peptide (P3) displayed higher ORAC activity than the low-molecular-weight fraction ($202.66{\mu}M\;TE/g$ vs $167.38{\mu}M\;TE/g$ of dry matter, respectively) (p<0.05). The peptide sequence of P3 was Cys-Cys-Cys-Cys-Ser-Val-Gln-Lys (888.30 Da). The novel peptide P3, at $250{\mu}g/mL$, also significantly inhibited HCT116 cell proliferation up to 25.24% through phosphorylation of ERK, JNK, and p38 kinase (p<0.05). Hence, antioxidant peptide P3 from Hanwoo beef extract can be used as an antioxidative and anticancer agent in the functional food industry.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.465-472
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• 2020

Colorectal cancer (CRC) is one of the most malignant type of cancers and its incidence is steadily increasing, due to life style factors that include western diet. Abnormal activation of canonical Wnt/β-catenin signaling pathway plays an important role in colorectal carcinogenesis. Therefore, targeting Wnt/β-catenin signaling has been considered a crucial strategy in the discovery of small molecules for CRC. In the present study, we found that Nodosin, an ent-kaurene diterpenoid isolated from Isodon serra, effectively inhibits the proliferation of human colon cancer HCT116 cells. Mechanistically, Nodosin effectively inhibited the overactivated transcriptional activity of β-catenin/T-cell factor (TCF) determined by Wnt/β-catenin reporter gene assay in HEK293 and HCT116 cells. The expression of Wnt/β-catenin target genes such as Axin2, cyclin D1, and survivin were also suppressed by Nodosin in HCT116 cells. Further study revealed that a longer exposure of Nodosin induced the G₂/M phase cell cycle arrest and subsequently apoptosis in HCT116 cells. These findings suggest that the anti-proliferative activity of Nodosin in colorectal cancer cells might in part be associated with the regulation of Wnt/β-catenin signaling pathway.

• 생명과학회지
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• 제22권1호
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• pp.55-61
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• 2012

Akt는 세포의 증식과 분화에 관여하며 많은 암종에서 과발현되어 있다는 것이 보고되었다. 본 연구에서는 Akt의 조절을 통한 셀레늄의 HT-29 세포의 세포증식억제 시너지효과를 확인하였다. 셀레늄을 농도별과 시간별로 처리하였을 때 HT-29 세포의 증식이 억제되었고, apoptosis가 일어남을 확인하였다. 셀레늄을 농도별로 처리하여 Western blotting 및 immunofluorescence를 실시한 결과 Akt의 인산화가 저해되었고 COX-2의 발현도 저해되었다. 또한 Akt 저해제인 LY294002를 처리한 결과, HT-29 대장암세포의 증식이 억제되었으며, LY294002를 셀레늄과 병행처리하였을 때 셀레늄에 의한 세포증식억제 효과가 더 강하게 나타나는 것을 확인하였다. Akt siRNA에 의한 Akt의 불활성화는 non-transfected 세포에 비하여 HT-29 세포의 성장을 더 강하게 억제하였으며, Akt가 불활성화 되었을 때 COX-2의 발현 역시 non-transfected 세포에 비하여 감소된 것을 확인하였다. 따라서 HT-29 세포에서 셀레늄의 세포증식억제 효과는 Akt와 COX-2 신호분자의 조절을 통해 일어나며, Akt 의 저해는 셀레늄의 대장암세포증식 억제에 시너지 효과를 나타냄을 확인하였다.

• Journal of Microbiology and Biotechnology
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• 제30권8호
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• pp.1214-1221
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• 2020

Esculetin 6-O-β-D-arabinofuranosyl-(1 → 6)-β-D-glucopyranoside (EAG) is a coumarin glycoside isolated from the stem bark of Fraxinus rhynchophylla. This study scrutinized the anti-proliferative activity of EAG on blood cancer-derived Jurkat leukemic cells. Cell viability assays in leukemic cancer cells determined that EAG possesses potent anti-proliferative effects. Moreover, treatment with EAG increased the proportion of apoptotic cells, resulted in cell cycle arrest being induced at the subG0/G1 phase, and reduced the proportion of cells present in the S phase. In addition, mitochondrial membrane potential was reduced by EAG in Jurkat cells. Additionally, EAG triggered apoptosis that was mediated by the downregulation of BCL-XL, p-IκBα, and p-p65 expressions in addition to the upregulation of cleaved Caspase 3 and BAX expressions. These findings revealed that the toxic effect of EAG was mediated by intracellular signal transduction pathways that involved a mechanism in which reactive oxygen species (ROS) were upregulated. Thus, this study concludes that EAG could potentially serve as a therapeutic agent for leukemia.

• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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• pp.4857-4861
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• 2016

Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R ($IC50=192{\mu}g/mL$) compared to K562 ($500{\mu}g/mL$) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.

• 한국가축번식학회지
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• 제17권4호
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• pp.279-285
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• 1994

The objective of the present study was to characterize the cell cycles of granulosa cell populations during follicular maturation in cattle by using flow cytometer. Granulosa cells were isolated from bovine preovulatory antral follicles of F1(>10mm), F2(5~20mm), F3(3~4mm) and F4(1~2mm) diameter and fixed and stained with fluorochromes that selectively bine to DNA. Flow cytometer equipped with a laser excitation system was used to analyze the intensity of fluorescence from stained cells. Forward angle light-scatter(FSC) and 90$^{\circ}$light-scatter(SSC) signals were adopted to measure the size and the granularity of granulosa cells. As a results of FSC/SSC analysis, granulosa cell populations(G1 phase of cell cycle) from each follicle were relatively regular in size and granularity, regardless of follicular size. However, their distribution in granularity was greater than that in size. Most of granulosa cell populations collected from each follicle were distributed in G0/G1, S and G2/M phases. As the follicles approached to ovulation the percentage of cells in the proliferative phases of cell cycle (S and G2/M) decreased significantly, but there was a concomitant increase in the percentage of granulosa cells in G1 phase. Therefore, these data indicate the proportion of main populations to cell cycle of granulosa cells may be changed from proliferative phase to G1 phase during follicular maturation in cattle.

• Molecules and Cells
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• 제45권9호
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• pp.631-639
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• 2022

Breast cancer is the leading cause of cancer-related death in women worldwide, despite medical and technological advancements. The RhoBTB family consists of three isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. RhoBTB1 and RhoBTB2 have been proposed as tumor suppressors in breast cancer. However, the roles of RhoBTB3 proteins are unknown in breast cancer. Bioinformatics analysis, including Oncomine, cBioportal, was used to evaluate the potential functions and prognostic values of RhoBTB3 and Col1a1 in breast cancer. qRT-PCR analysis and immunoblotting assay were performed to investigate relevant expression. Functional experiments including proliferation assay, invasion assay, and flow cytometry assay were conducted to determine the role of RhoBTB3 and Col1a1 in breast cancer cells. RhoBTB3 mRNA levels were significantly up-regulated in breast cancer tissues as compared to in adjacent normal tissues. Moreover, RhoBTB3 expression was found to be associated with Col1a1 expression. Decreasing RhoBTB3 expression may lead to decreases in the proliferative and invasive properties of breast cancer cells. Further, Col1a1 knockdown in breast cancer cells limited the proliferative and invasive ability of cancer cells. Knockdown of RhoBTB3 may exert inhibit the proliferation, migration, and metastasis of breast cancer cells by repressing the expression of Col1a1, providing a novel therapeutic strategy for treating breast cancer.

• Natural Product Sciences
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• 제10권2호
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• pp.74-79
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• 2004

Dietary flavonoids are currently receiving considerable attention in developing novel cancer-preventive approaches because of their potential capacities to actively induce apoptosis of cancer cells. In our previous report, a flavonoid fraction, which consisted mainly of protocatechuic acid, fustin, fisetin, sulfuretin, and butein and named RCMF (RVS chloroform-methanol fraction), was prepared from a crude acetone extract of Rhus verniciflua Stokes (RVS) that is traditionally used as food additive and herbal medicine. In this study, we evaluated the effects of the RCMF on cell proliferation and apoptosis using SV40-transformed tumorigenic hepatocytes, BNL SV A.8. Tritium uptake assay showing the proliferative capacity of the cells was strongly suppressed in the presence of RCMF. This anti-proliferative effect was further confirmed through trypan blue exclusion. RCMF-mediated suppression of cell growth was verified to be apoptotic, based on the increase in DNA fragmentation, low fluorescence intensity in nuclei after propidium iodide staining, and the appearance of DNA laddering. Collectively, this study demonstrated that RCMF can be approached as a potential agent that is capable of significantly inhibiting cell growth of hepatic cancer cells.

• Molecules and Cells
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• 제39권12호
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• pp.847-854
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• 2016

The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slowergrowing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates that altered metabolism plays key roles in supporting proliferation-independent functions of cancer such as cell survival within the ischemic and acidic tumor microenvironment, immune system evasion, and maintenance of the cancer stem cell state. As these aspects of cancer cell metabolism are critical for tumor maintenance yet are less likely to be relevant in normal cells, they represent attractive targets for cancer therapy.