Luteolin overcomes resistance to benzyl isothiocyanate-induced apoptosis in human colorectal cancer HCT-116 cells

The goal of this study was to investigate the effect of the Panax notoginseng ethanol extract (PNEE) on the regulation of human colorectal cancer (CRC) metastasis. The migratory, invasive, and adhesive abilities and the expression of metastasis-associated regulatory molecules in cultured human CRC cells (HCT-116) treated with the PNEE were analyzed in this study. The migratory and invasive abilities of HCT-116 cells were reduced after PNEE treatment. The incubation of HCT-116 cells with the PNEE for 24 h decreased MMP-9 expression and increased E-cadherin expression compared with the control group. The adhesion reaction assay indicated that treatment with the PNEE led to significantly decreased HCT-116 adhesion to endothelial cells (EA.hy926 cells). The integrin-1 protein levels in HCT-116 cells were significantly decreased following treatment with the PNEE. Similarly, the protein levels of E-selectin and intercellular adhesion molecule-1 (ICAM-1) were significantly decreased by treatment of the EA.hy926 endothelial cells with PNEE. A scanning electron microscope (SEM) examination indicated that HCT-116 cells treated with LPS combined with the PNEE had a less flattened and retracted shape compared with LPS-treated cells, and this change in shape was found to be a phenomenon of extravasation invasion. The transepithelial electrical resistance (TEER) of the EA.hy926 endothelial cell monolayer increased after incubation with the PNEE for 24 h. A cell-cell permeability assay indicated that HCT-116 cells treated with the PNEE displayed significantly reduced levels of phosphorylated VE-cadherin (p-VE-cadherin). These results demonstrate the antimetastatic properties of the PNEE and show that the PNEE affects cells by inhibiting cell migration, invasion, and adhesion and regulating the expression of metastasis-associated signaling molecules.

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A multidrug resistance‐associated protein inhibitor is a potential enhancer of the benzyl isothiocyanate‐induced apoptosis induction in human colorectal cancer cells

Journal of Biochemical and Molecular Toxicology ◽

10.1002/jbt.22791 ◽

2021 ◽

Author(s):

Qifu Yang ◽

Toshiyuki Nakamura ◽

Masayuki Seto ◽

Miku Miyagawa ◽

Wensi Xu ◽

...

Keyword(s):

Colorectal Cancer ◽

Multidrug Resistance ◽

Cancer Cells ◽

Apoptosis Induction ◽

Protein Inhibitor ◽

Human Colorectal Cancer ◽

Benzyl Isothiocyanate ◽

Colorectal Cancer Cells ◽

Induced Apoptosis ◽

Human Colorectal Cancer Cells

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Activations of Both Extrinsic and Intrinsic Pathways in HCT 116 Human Colorectal Cancer Cells Contribute to Apoptosis through p53-Mediated ATM/Fas Signaling byEmilia sonchifoliaExtract, a Folklore Medicinal Plant

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/178178 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 20

Author(s):

Yu-Hsuan Lan ◽

Jo-Hua Chiang ◽

Wen-Wen Huang ◽

Chi-Cheng Lu ◽

Jing-Gung Chung ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Major Constituent ◽

Herbaceous Plant ◽

Human Colorectal Cancer ◽

Colorectal Cancer Cells ◽

Fas Signaling ◽

Hct 116 ◽

Hct 116 Cells ◽

Human Colorectal Cancer Cells

Emilia sonchifolia(L.) DC (Compositae), an herbaceous plant found in Taiwan and India, is used as folk medicine. The clinical applications include inflammation, rheumatism, cough, cuts fever, dysentery, analgesic, and antibacteria. The activities ofEmilia sonchifoliaextract (ESE) on colorectal cancer cell death have not been fully investigated. The purpose of this study explored the induction of apoptosis and its molecular mechanisms in ESE-treated HCT 116 human colorectal cancer cellsin vitro. The methanolic ESE was characterized, and γ-humulene was formed as the major constituent (63.86%). ESE induced cell growth inhibition in a concentration- and time-dependent response by MTT assay. Apoptotic cells (DNA fragmentation, an apoptotic catachrestic) were found after ESE treatment by TUNEL assay and DNA gel electrophoresis. Alternatively, ESE stimulated the activities of caspase-3, -8, and -9 and their specific caspase inhibitors protected against ESE-induced cytotoxicity. ESE promoted the mitochondria-dependent and death-receptor-associated protein levels. Also, ESE increased ROS production and upregulated the levels of ATM, p53, and Fas in HCT 116 cells. Strikingly, p53 siRNA reversed ESE-reduced viability involved in p53-mediated ATM/Fas signaling in HCT 116 cells. In summary, our result is the first report suggesting that ESE may be potentially efficacious in the treatment of colorectal cancer.

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Inhibitory Effects of Peptide Lunasin in Colorectal Cancer HCT-116 Cells and Their Tumorsphere-Derived Subpopulation

International Journal of Molecular Sciences ◽

10.3390/ijms21020537 ◽

2020 ◽

Vol 21 (2) ◽

pp. 537 ◽

Cited By ~ 9

Author(s):

Samuel Fernández-Tomé ◽

Fei Xu ◽

Yanhui Han ◽

Blanca Hernández-Ledesma ◽

Hang Xiao

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Kinase Inhibitor ◽

G1 Phase ◽

Inhibitory Effects ◽

Cyclin Dependent Kinase Inhibitor ◽

Hct 116 ◽

Hct 116 Cells ◽

Induced Apoptosis ◽

Chemopreventive Activity

The involvement of cancer stem-like cells (CSC) in the tumor pathogenesis has profound implications for cancer therapy and chemoprevention. Lunasin is a bioactive peptide from soybean and other vegetal sources with proven protective activities against cancer and other chronic diseases. The present study focused on the cytotoxic effect of peptide lunasin in colorectal cancer HCT-116 cells, both the bulk tumor and the CSC subpopulations. Lunasin inhibited the proliferation and the tumorsphere-forming capacity of HCT-116 cells. Flow cytometry results demonstrated that the inhibitory effects were related to apoptosis induction and cell cycle-arrest at G1 phase. Moreover, lunasin caused an increase in the sub-GO/G1 phase of bulk tumor cells, linked to the apoptotic events found. Immunoblotting analysis further showed that lunasin induced apoptosis through activation of caspase-3 and cleavage of PARP, and could modulate cell cycle progress through the cyclin-dependent kinase inhibitor p21. Together, these results provide new evidence on the chemopreventive activity of peptide lunasin on colorectal cancer by modulating both the parental and the tumorsphere-derived subsets of HCT-116 cells.

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Ferula pseudalliacea induces apoptosis in human colorectal cancer HCT-116 cells via mitochondria-dependent pathway

Archives of Physiology and Biochemistry ◽

10.1080/13813455.2018.1455710 ◽

2018 ◽

Vol 125 (3) ◽

pp. 284-291 ◽

Cited By ~ 2

Author(s):

Hadi Bamehr ◽

Massoud Saidijam ◽

Dara Dastan ◽

Razieh Amini ◽

Mona Pourjafar ◽

...

Keyword(s):

Colorectal Cancer ◽

Human Colorectal Cancer ◽

Hct 116 ◽

Hct 116 Cells ◽

Dependent Pathway

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Post-transcriptional regulation of the tumor suppressor p53 by a novel miR-27a, with implications during hypoxia and tumorigenesis

Biochemical Journal ◽

10.1042/bcj20160359 ◽

2016 ◽

Vol 473 (20) ◽

pp. 3597-3610 ◽

Cited By ~ 5

Author(s):

Raihana Maqbool ◽

Saife Niaz Lone ◽

Mahboob Ul Hussain

Keyword(s):

Colorectal Cancer ◽

Tumor Suppressor ◽

Tumor Suppressor Protein ◽

Luciferase Reporter ◽

Human Colorectal Cancer ◽

P53 Expression ◽

Tumor Suppressor Protein P53 ◽

Protein P53 ◽

Hct 116 ◽

Hct 116 Cells

The tumor suppressor protein p53 is intricately regulated by various signaling molecules, including non-coding small RNAs, called microRNAs (miRNAs). The in silico analysis and the inverse expression status in various cell lines raised the possibility of miR-27a being a new regulator of p53. Using luciferase reporter assay and various mutational and functional analysis, we identified two putative binding sites of miR-27a on the 3′-UTR of p53. The overexpression of miR-27a in the human colorectal cancer cell line HCT-116+/+ resulted in the decreased expression of the endogenous p53 protein levels. During hypoxia of the HCT-116+/+ cells, p53 showed increased accumulation after 3 h, and the levels were significantly up-regulated until 24 h of hypoxia. The p53 expression dynamics during hypoxia of the HCT-116+/+ cells were found to be inversely regulated by miR-27a expression. Moreover, using a cell viability assay, we established that after 3 h of hypoxia, the accumulation of p53 results in a decreased number of the viable HCT-116+/+ cells and the overexpression of miR-27a resulted in an increased number of viable HCT-116+/+ cells with a concomitant decrease in p53 expression. Additionally, our data indicated that miR-27a and p53 depict inverse expression dynamics in 50% of the human colorectal cancer samples studied, when compared with that in the adjacent normal samples. Our data established that miR-27a and the tumor suppressor protein p53 are part of the same signaling network that has important implications during hypoxia and tumorigenesis.

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