• KSBB Journal
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• 제32권3호
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• pp.212-217
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• 2017

Colorectal cancer is a leading cause of cancer mortality worldwide. Many studies show that most cases of human colorectal cancer arise from adenomatous polyps, which are usually dysplastic, nonmalignant precursor lesions; however, accumulation of multiple somatic mutations leads some to develop into advanced adenoma, which ultimately progresses to an invasive colorectal cancer. Notwithstanding the efforts made to improve chemotherapy, most colorectal cancers are unresponsive to this form of treatment, and malignant colorectal cancers remain incurable. To reduce the incidence of colorectal cancer mortality, further studies to improve colorectal cancer treatment are needed. Here, we show that Globefish homogenate suppresses the growth of Caco-2 human colorectal cancer cells, and that the homogenate inhibits Caco-2 cell proliferation in a dose-dependent manner. These data suggest that Globefish homogenate may suppress colorectal cancer development.

• Radiation Oncology Journal
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• 제28권3호
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• pp.147-154
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• 2010

목 적: 대장암 세포에서 epidermal growth factor receptor (EGFR) 저해제인 nimotuzumab에 의한 방사선 민감도 증진 효과를 살펴보고자 한다. 대상 및 방법: 총 4종류의 인간 유래 대장암 세포주인 HCT-8, LoVo, WiDr, HCT-116를 nimotuzumab과 방사선을 병합 처리한 후 세포증식, 생존율, 세포주기 진행에 미치는 영향을 MTT, clonogenic survival assay, flow cytometry와 western blot을 통해 분석하였다. 결 과: 대장암 세포주에서 nimotuzumab에 의해 EGFR 인산화가 억제됨을 확인하였고 이러한 조건에서 nimotuzumab이 HCT-116을 제외한 나머지 3종류의 대장암 세포주의 방사선 민감도를 증진시킴을 확인하였다. 반면에, nimotuzumab은 방사선 조사와 무관하게 대장암 세포의 증식이나 세포 주기에는 아무런 영향을 미치지 않았다. 결 론: Nimotuzumab은 EGFR에 의한 세포 생존 신호 전달을 억제함으로써 대장암 세포의 방사선에 대한 민감도를 증가시켰다. 본 연구는 대장암의 방사선 치료에 EGFR 특이적 저해제인 nimotuzumab의 임상 적용 근거를 제공하였다.

• 한국자원식물학회지
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• 제29권3호
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• pp.281-288
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• 2016

Apoptosis has been regarded as a therapeutic target because apoptosis is typically disturbed in human cancer. Silymarin found in the seeds of the milk thistle (Silybum marianum) has been reported to exert anti-cancer properties through apoptosis. This study was performed to investigate the molecular target for silymarin-mediated apoptosis in human colorectal cancer cells. Silymarin reduced the cell viability and induced an apoptosis in human colorectal cancer cells. ATF3 overexpression increased PARP cleavage by silymarin. Increased ATF3 expression in both protein and mRNA was observed in silymarin-treated cells. In addition, silymarin increased the luciferase activity of ATF3 promoter. Inhibition of JNK and IκK-α blocked silymarin-mediated ATF3 expression. The results suggest that silymarin induces apoptosis through JNK and IκKα-dependent ATF3 expression in human colorectal cancer cells.

• BMB Reports
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• 제56권10호
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• pp.557-562
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• 2023

Dysregulation of the E3 ubiquitin ligase Parkin has been linked to various human cancers, indicating that Parkin is a tumor suppressor protein. However, the mechanisms of action of Parkin remain unclear to date. Thus, we aimed to elucidate the mechanisms of action of Parkin as a tumor suppressor in human lung and colorectal cancer cells. Results showed that Parkin overexpression reduced the viability of A549 human lung cancer cells by inducing G2/M cell cycle arrest. In addition, Parkin caused DNA damage and ATM (Ataxia telangiectasia mutated) activation, which subsequently led to p53 activation. It also induced the p53-mediated upregulation of p21 and downregulation of cyclin B1. Moreover, Parkin suppressed the proliferation of HCT-15 human colorectal cancer cells by a mechanism similar to that in A549 lung cancer cells. Taken together, our results suggest that the tumor-suppressive effects of Parkin on lung and colorectal cancer cells are mediated by DNA damage/p53 activation/cyclin B1 reduction/cell cycle arrest.

• 한국자원식물학회지
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• 제29권3호
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• pp.297-304
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• 2016

The seed of safflower (Carthamus tinctorius L) has been reported to suppress human cancer cell proliferation. However, the mechanisms by which safflower seed inhibits cancer cell proliferation have remained nuclear. In this study, the inhibitory effect of the safflower seed (SS) on the proliferation of human colorectal cancer cells and the potential mechanism of action were examined. SS inhibited markedly the proliferation of human colorectal cancer cells (HCT116, SW480, LoVo and HT-29). In addition, SS suppressed the proliferation of human breast cancer cells (MDA-MB-231 and MCF-7). SS treatment decreased cyclin D1 protein level in human colorectal cancer cells and breast cancer cells. But, SS-mediated downregulated mRNA level of cyclin D1 was not observed. Inhibition of proteasomal degradation by MG132 attenuated cyclin D1 downregulation by SS and the half-life of cyclin D1 was decreased in SS-treated cells. In addition, SS increased cyclin D1 phosphorylation at threonine-286 and a point mutation of threonine-286 to alanine attenuated SS-mediated cyclin D1 degradation. Inhibition of ERK1/2 by PD98059 suppressed cyclin D1 phosphorylation and downregulation of cyclin D1 by SS. In conclusion, SS has anti-proliferative activity by inducing cyclin D1 proteasomal degradation through ERK1/2-dependent threonine-286 phosphorylation of cyclin D1. These findings suggest that possibly its extract could be used for treating colorectal cancer.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2020년도 춘계학술대회
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• pp.89-89
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• 2020

In this study, we evaluated the effect of the extracts from Lonicera caerulea leaves (LCLE), branches (LCBE) and fruits (LCFE) on the cell growth and migration in human colorectal cancer cells, HCT116 and SW480 cells. LCLE and LCBE dose- and time-dependently inhibited the proliferation of HCT116 and SW480 cells. However, LCFE did not affect the proliferation of HCT116 and SW480 cells. In addition, LCLE and LCBE dramatically cell migration and wound healing in HCT116 cells. LCLE and LCBE decreased β-catenin protein level but not mRNA level in HCT116 and SW480 cells. Furthermore, LCLE decreased TCF4 level in both protein and mRNA level in HCT116 and SW480 cells. However, LCBE decreased TCF4 protein level but not mRNA level in HCT116 and SW480 cells. Based on these findings, LCLE and LCBE may inhibit the cell proliferation and migration through blocking Wnt signaling activation in human colorectal cancer cells. Therefore, LCLE and LCBE may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9185-9190
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• 2014

Cyclo-oxygenase-2(Cox-2), a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth. Therefore, a better understanding of the regulatory mechanisms of Cox-2 could lead to novel targeted cancer therapies. MicroRNAs are strongly implicated in colorectal cancer but their specific roles and functions have yet to be fully elucidated. MiR-1297 plays an important role in lung adenocarcinoma and laryngeal squamous cell carcinoma, but its significance in colorectal cancer (CRC) has yet to be reported. In our present study, we found miR-1297 to be down regulated in both CRC-derived cell lines and clinical CRC samples, when compared with normal tissues. Furthermore, miR-1297 could inhibit human colorectal cancer LOVO and HCT116 cell proliferation, migration, and invasion in vitro and tumorigenesis in vivo by targeting Cox-2. Moreover, miR-1297 directly binds to the 3'-UTR of Cox-2, and the expression level was drastically decreased in LOVO and HCT116 cells following overexpression of miR-1297. Additionally, Cox-2 expression levels are inversely correlated with miR-1297 expression in human colorectal cancer xenograft tissues. These results imply that miR-1297 has the potential to provide a new approach to colorectal cancer therapy by directly inhibiting Cox-2 expression.

• 대한한의학방제학회지
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• 제23권1호
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• pp.101-110
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• 2015

Objectives : The purpose of this study was to investigate the anti-cancer effects of Oldenlandia diffusa extract on WiDr human colorectal adenocarcinoma cells. Methods : We examined cell death by (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) MTT assay and the caspase 3 and 9 activity assay with Oldenlandia diffusa extract. To examine the inhibitory effects of Oldenlandia diffusa extract, we performed a cell cycle (sub-G1) analysis and mitochondrial membrane potential for the WiDr cells after 24 hours with Oldenlandia diffusa extract. Results : 1. Oldenlandia diffusa extract induced cell death in WiDr cells. 2. The sub-G1 peak was increased by Oldenlandia diffusa extract in WiDr cells. 3. Oldenlandia diffusa extract leads to increase the mitochondrial membrane depolarization in WiDr cells. 4. Oldenlandia diffusa extract increases caspase 3 and 9 activities in WiDr cells. 5. Oldenlandia diffusa extract combined with several anti-cancer drugs (paclitaxel, 5-fluorouracil, cisplatin, ectoposide, doxorubicin and docetaxel) markedly inhibited the growth of WiDr cells compared to Oldenlandia diffusa extract and anti-cancer drugs alone. Conclusions : Oldenlandia diffusa extract has an apoptotic role in human colorectal cancer cells and a potential role in developing therapeutic agents against colorectal cancer.

• 대한의생명과학회지
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• 제17권3호
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• pp.177-184
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• 2011

Potassium cyanate (KOCN) is an inorganic compound and induces the carbamylation of proteins with cytotoxic effects on human cells. Although there is a potential cytotoxic molecule, the role of KOCN on the apoptosis of cancer cell is not well understood. The present study investigated the effects of KOCN on the human colorectal cancer cell line, HCT 116 cells. To understand the anti-cancer effect of KOCN on HCT 116 cells, we examined alteration of apoptosis, the intracellular $Ca^{2+}$ concentration, the intracellular signaling pathway and generation of reactive oxygen species (ROS) in these cells treated with KOCN. The apoptosis of HCT 116 cells was induced by KOCN in a dose-dependent manner at 24 hours and 48 hours, respectively. The apoptosis was processed via the cleavage of poly ADP-ribose polymerase (PARP) and activation of caspase 3 in HCT 116 cells. KOCN induced the elevation of intracellular $Ca^{2+}$ concentration and changed the expressions of Bcl-2 family proteins. The pro-apoptotic Bax was continuously up-regulated, and the anti-apoptotic Bcl-2 was down-regulated by KOCN. KOCN also induced the hyperpolarization of mitochondria and the generation of ROS in HCT 116 cells. Taken together, these results indicate that KOCN induces the apoptosis of HCT 116 cells by disruption of $Ca^{2+}$ homeostasis and via mitochondrial pathway. This study provides the compound that may be used as a potent agent for the treatment of colorectal cancer.

• Nutrition Research and Practice
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• 제18권1호
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• pp.62-77
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• 2024

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide with a high recurrence rate. Oxaliplatin (OXA) resistance is one of the major reasons hindering CRC therapy. β-Carotene (BC) is a provitamin A and is known to have antioxidant and anticancer effects. However, the combined effect of OXA and BC has not been investigated. Therefore, this study investigated the anticancer effects and mechanism of the combination of OXA and BC on CRC. MATERIALS/METHODS: In the present study, the effects of the combination of OXA and BC on cell viability, cell cycle arrest, and cancer stemness were investigated using HCT116, HT29, OXA-resistant cells, and human CRC organoids. RESULTS: The combination of OXA and BC enhanced apoptosis, G₂/M phase cell cycle arrest, and inhibited cancer cell survival in human CRC resistant cells and CRC organoids without toxicity in normal organoids. Cancer stem cell marker expression and self-replicating capacity were suppressed by combined treatment with OXA and BC. Moreover, this combined treatment upregulated apoptosis and the stem cell-related JAK/STAT signaling pathway. CONCLUSIONS: Our results suggest a novel potential role of BC in reducing resistance to OXA, thereby enhances the anticancer effects of OXA. This enhancement is achieved through the regulation of cell cycle, apoptosis, and stemness in CRC.