• Title/Summary/Keyword: HCT 116 cells

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Picropodophyllotoxin Induces G1 Cell Cycle Arrest and Apoptosis in Human Colorectal Cancer Cells via ROS Generation and Activation of p38 MAPK Signaling Pathway

  • Lee, Seung-On;Kwak, Ah-Won;Lee, Mee-Hyun;Seo, Ji-Hye;Cho, Seung-Sik;Yoon, Goo;Chae, Jung-Il;Joo, Sang Hoon;Shim, Jung-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.31 no.12
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    • pp.1615-1623
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    • 2021
  • Picropodophyllotoxin (PPT), an epimer of podophyllotoxin, is derived from the roots of Podophyllum hexandrum and exerts various biological effects, including anti-proliferation activity. However, the effect of PPT on colorectal cancer cells and the associated cellular mechanisms have not been studied. In the present study, we explored the anticancer activity of PPT and its underlying mechanisms in HCT116 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to monitor cell viability. Flow cytometry was used to evaluate cell cycle distribution, the induction of apoptosis, the level of reactive oxygen species (ROS), assess the mitochondrial membrane potential (Δψm), and multi-caspase activity. Western blot assays were performed to detect the expression of cell cycle regulatory proteins, apoptosis-related proteins, and p38 MAPK (mitogen-activated protein kinase). We found that PPT induced apoptosis, cell cycle arrest at the G1 phase, and ROS in the HCT116 cell line. In addition, PPT enhanced the phosphorylation of p38 MAPK, which regulates apoptosis and PPT-induced apoptosis. The phosphorylation of p38 MAPK was inhibited by an antioxidant agent (N-acetyl-L-cysteine, NAC) and a p38 inhibitor (SB203580). PPT induced depolarization of the mitochondrial inner membrane and caspase-dependent apoptosis, which was attenuated by exposure to Z-VAD-FMK. Overall, these data indicate that PPT induced G1 arrest and apoptosis via ROS generation and activation of the p38 MAPK signaling pathway.

Cytotoxic Flavonoids from the Whole Plants of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (구절초에서 분리한 Flavonoids의 인체암 세포주에 대한 세포독성 효과)

  • Kwon, Hyun-Sook;Ha, Tae-Joung;Hwang, Seon-Woo;Jin, Young-Min;Nam, Sang-Hae;Park, Ki-Hun;Yang, Min-Suk
    • Journal of Life Science
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    • v.16 no.5
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    • pp.746-749
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    • 2006
  • Two known flavonoids, luteolin (1) and acacetin (2) were isolated from a $CHCI_3$ soluble fraction of the whole plants of Chrysanthemum zawadskii Herbich var. latilobum Kitamura, and their structures were determined by NMR analysis. The luteolin (1) was isolated from this plant for the first time. These compounds were examined for their in vitro cytotoxic activities against four human cancer cell lines including HCT116 (colon), UO-31 (renal), PC-3 (prostate) and A549 (lung) by sulforhodamine B(SRB) assay. Acacetin (2) showed significant cytotoxic activity against HCT116 and UO-31 cells with an $IC_{50}$ of 2.44 and $2.89\;{\mu}g/ml$, respectively.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells

  • Xiong, Wei;Jiang, Yong-Xin;Ai, Yi-Qin;Liu, Shan;Wu, Xing-Rao;Cui, Jian-Guo;Qin, Ji-Yong;Liu, Yan;Xia, Yao-Xiong;Ju, Yun-He;He, Wen-Jie;Wang, Yong;Li, Yun-Fen;Hou, Yu;Wang, Li;Li, Wen-Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3395-3402
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    • 2015
  • Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

Ginsenosides from the fruits of Panax ginseng and their cytotoxic effects on human cancer cell lines (인삼(Panax ginseng) 열매로부터 분리한 ginsenoside의 동정 및 암세포독성 효과)

  • Gwag, Jung Eun;Lee, Yeong-Geun;Hwang-Bo, Jeon;Kim, Hyoung-Geun;Oh, Seon Min;Lee, Dae Young;Baek, Nam-In
    • Journal of Applied Biological Chemistry
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    • v.61 no.4
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    • pp.371-377
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    • 2018
  • The fruits of Panax ginseng were extracted with 80% aqueous MeOH and the concentrates were partitioned into EtOAc, n-BuOH, and $H_2O$ fractions. The repeated $SiO_2$ and octadecyl $SiO_2$ column chromatographies for the EtOAc fraction led to isolation of five ginsenosides. The chemical structures of these compounds were determined as ginsenoside F1 (1), ginsenoside F2 (2), ginsenoside F3 (3), ginsenoside Ia (4), notoginsenoside Fe (5) based on spectroscopic analyses including nuclear magnetic resonance, MS, and infrared. Compounds 2-5 were isolated for the first time from the fruits of P. ginseng in this study. All isolated compounds were evaluated for cytotoxic activities against human cancer cell lines such as HCT-116, SK-OV-3, human cervix adenocarcinoma (HeLa), HepG2, and SK-MEL-5. Among them compounds 2, 4, and 5 showed significant cytotoxicity on cancer cells. Compound 2 exhibited cytotoxicity on SK-MEL-5, HepG2, and HeLa cells with $IC_{50}$ values of 82.8, 86.8, and $78.3{\mu}M$, respectively. Compound 4 showed cytotoxicity on HCT-116, SK-MEL-5, SK-OV-3, HepG2, and HeLa cells with $IC_{50}$ values of 24.5, 25.4, 26.3, 22.0, and $24.9{\mu}M$, respectively. Compound 5 did on SK-MEL-5 cell with $IC_{50}$ value of $81.7{\mu}M$. The cytotoxicity of ginsenoside 2, 4, and 5 isolated from the fruits of Panax ginseng showed strong inhibition effect against on cancer cells, all of which have a glucopyranosyl moiety on C-3.

Enhancement of Anti-tumorigenic Polysaccharide Production, Adhesion, and Branch Formation of Bifidobacterium bifidum BGN4 by Phytic Acid

  • Ku, Seock-Mo;You, Hyun-Ju;Ji, Geun-Eog
    • Food Science and Biotechnology
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    • v.18 no.3
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    • pp.749-754
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    • 2009
  • The polysaccharide (BB-pol) extracted from Bifidobacterium bifidum BGN4 showed growth inhibitory effects on several colon cancer cell lines such as HT-29 and HCT-116. To increase the yield of polysaccharide, B. bifidum BGN4 was cultured in various culture media with different compositions. When B. bifidum BGN4 was cultured in modified MRS broth containing phytic acid, the cells showed increased branch formation and enlarged morphology. The content of total carbohydrate and the ability of adhesion to intestinal epithelial cells were also increased by phytic acid. The polysaccharide obtained from the cells grown in the presence of phytic acid inhibited the proliferation of cancer cell lines such as HT-29 and MCF-7 cells but not normal colon cell line, FHC. Taken together, Bifidobacterium grown in the presence of phytic acid may confer enhanced beneficial function for the host.