• Journal of Nutrition and Health
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• v.52 no.2
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• pp.157-167
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• 2019

Purpose: This study examined the antioxidant and cancer cell growth inhibitory activities of an ethanol extract and different solvent fractions of Mesembryanthemum crystallinum L. (ice plant). Methods: The ice plant was freeze-dried, extracted with 99.9% ethanol, and then fractionated with hexane, ethyl acetate, butanol, and water. The total polyphenol content (TPC), total carotenoid content (TCC), 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity (RSA), and ferric reducing antioxidant power (FRAP) were measured. Assays using 2',7'-dichlorofluorescin-diacetate and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide were performed to measure the intracellular reactive oxygen species (ROS) and cell growth, respectively. Annexin V/propidium iodide staining and cell cycle analysis were performed for the detection of apoptosis and cell cycle arrest. Results: TPC, TCC, RSA, and FRAP of the ethanol extract (EE) were 3.7 mg gallic acid equivalent/g, $13.2{\mu}g/g$, 21.0% (at a concentration of 5 mg/mL), and 21.0% (at a concentration of 5 mg/mL), respectively. Among the different solvent fractions, the butanol fraction (BF) showed the highest TPC (5.4 mg gallic acid equivalent/g), TCC ($86.6{\mu}g/g$), RSA (34.9% at 5 mg/mL), and FRAP (80.8% at 5 mg/mL). Treatment of HCT116 human colon cancer cells with EE and BF at concentrations of 250 and $500{\mu}g/mL$ reduced the levels of intracellular ROS. Concomitantly, EE and BF resulted in the dose-dependent inhibition of cell growth (at the concentrations of 125, 250, and $500{\mu}g/mL$ for 24 ~ 48 h) and the induction of apoptosis (at the concentrations of 250 and $500{\mu}g/mL$ for 48 h) in HCT116 cells. An increased G2/M cell population was also found in the BF-treated cells. Conclusion: These results suggest that ice plant possesses antioxidant and growth inhibitory activities in colon cancer cells.

• Nutrition Research and Practice
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• v.9 no.1
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• pp.11-16
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• 2015

BACKGROUND/OBJECTIVES: Perilla frutescens Britton leaves are a commonly consumed vegetable in different Asian countries including Korea. Cancer is a major cause of human death worldwide. The aim of the current study was to investigate the inhibitory effects of ethanol extract of perilla leaf (PLE) against important characteristics of cancer cells, including unrestricted growth, resisted apoptosis, and activated metastasis, using human cancer cells. MATERIALS/METHODS: Two human cancer cell lines were used in this study, HCT116 colorectal carcinoma cells and H1299 non-small cell lung carcinoma cells. Assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide were performed for measurement of cell growth. Soft agar and wound healing assays were performed to determine colony formation and cell migration, respectively. Nuclear staining and cell cycle analysis were performed for assessment of apoptosis. Fibronectin-coated plates were used to determine cell adhesion. RESULTS: Treatment of HCT116 and H1299 cells with PLE resulted in dose-dependent inhibition of growth by 52-92% (at the concentrations of 87.5, 175, and $350{\mu}g/ml$) and completely abolished the colony formation in soft agar (at the concentration of $350{\mu}g/ml$). Treatment with PLE at the $350{\mu}g/ml$ concentration resulted in change of the nucleus morphology and significantly increased sub-G1 cell population in both cells, indicating its apoptosis-inducing activity. PLE at the concentration range of 87.5 to $350{\mu}g/ml$ was also effective in inhibiting the migration of H1299 cells (by 52-58%) and adhesion of both HCT116 and H1299 cells (by 25-46%). CONCLUSIONS: These results indicate that PLE exerts anti-cancer activities against colon and lung cancers in vitro. Further studies are needed in order to determine whether similar effects are reproduced in vivo.

• BMB Reports
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• v.38 no.5
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• pp.619-623
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• 2005

The efficacy of chemotherapeutic agents on tumor cells has been shown to be modulated by tumor suppressor gene p53 and its target genes such as Bcl-2 family members (Bax, Noxa, and PUMA). However, various chemotherapeutic agents can induce cell death in tumor cells that do not express the functional p53, suggesting that some chemotherapeutic agents may induce cell death in a p53-independent pathway. Here we showed that etoposide can induce the similar degree of cell death in p53-deficient HCT 116 cells, whereas 5'-FU-mediated cell death is strongly dependent on the existence of functional p53 in HCT 116 cells. Further, we provide the evidence that etoposide can induce the cytochrome c release from isolated mitochondria, and etoposide-induced cytochrome c release is not accompanied with the large amplitude swelling of mitochondria. These data suggest that etoposide can directly induce the mitochondrial dysfunction irrespective of p53 status, and it may, at least in part, account for the p53-independent pathway in cell death induced by chemotherapeutic agents.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2795-2798
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• 2012

Objective: This study is conducted to evaluate the effects of anti-HER-2${\times}$anti-CD3 bi-specific antibodies(BsAb) on HER-2/neuover-expressing human colorectal carcinoma cells. Methods: Growth was assessed by MTT assays after exposure of HCT-116 cells to Herceptin, anti-CD3 and BsAb antibodies. Immunocytochemistry was applied to test the HER-2 level of HCT-116. In a nude mouse model, HER-2${\times}$CD3 BsAb was combined with effector cells (peripheral blood lymph cells from normal human being) for observations on in Vivo growth of tumors. Results: Compared with the control group, using effector cells combined with anti-CD3 McAb, Herceptin or HER2${\times}$CD3 BsAb, tumor cell growth in vitro and in vivo was significantly inhibited (P<0.05), most remarkably in the HER2${\times}$CD3 BsAb case. The growth of xenografts with HER2${\times}$CD3 BsAb combined with effector cells was also significantly inhibited when compared with the anti-CD3 McAb or Herceptin groups (P<0.05). Conclusion: HER-2/neu might be a useful target for immunotherapy in colorectal carcinoma, anti-HER2${\times}$anti-CD3 BsAb exerting clear anti-tumor effects.

• Journal of Life Science
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• v.29 no.10
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• pp.1080-1085
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• 2019

Nelumbo nucifera, also known as sacred lotus, has mainly been used as a food throughout the Asian countries. In the present study, we prepared the ethanol extracts from leaf (NL), seed (NS), and seedpod (NSP) of Nelumbo nucifera and investigated their anti-proliferative and pro-apoptotic activities in human colorectal cancer HCT116 cells. NL, NS, and NSP decreased cell viabilities in a dose-dependent manner. All extracts increased the expression of non-steroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) as well as NAG-1 protein. And also, NL induced the expression of pro-apoptotic NAG-1 protein and PARP cleavage in a time-dependent manner. The PARP cleavage induced by NL treatment, was recovered in part by the transfection of NAG-1 siRNA. We also evaluated the effects of neferine, one of bioactive components of Nelumbo nucifera, on the proliferation and apoptosis in HCT116 cells. It also decreased cell viability in a dose-dependent manner, and induced the expression of pro-apoptotic NAG-1 protein and PARP cleavage in a dose- and time-dependent manner. In addition, PARP cleavage was recovered in part by the transfection of NAG-1 siRNA, indicating that NAG-1 may be one of the genes responsible for apoptosis induced by neferine. Overall, our findings may contribute to understand the molecular mechanisms of anti-proliferative and pro-apoptotic effects mediated by Nelumbo nucifera and neferine.

• Journal of Life Science
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• v.24 no.9
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• pp.967-972
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• 2014

In the present study, we prepared eighty-five different kinds of lees extracts and their solvent fractions and investigated their anti-proliferative activities against human colorectal cancer HCT116 cells. HCT116 cells were treated with eighty-five solvent fractions of lees extracts and then cell viability was measured using MTS assay. Among the treated solvent fractions, three solvent fractions (KSD-E1-3, KSD-E2-3, and KSD-E4-3) were selected based on cell viability assay. In addition, we performed an oligo DNA microarray analysis to analyze the gene expression changes by treatment of KSD-E1-3 in HCT116 cells. Among the upregulated genes, we selected 4 genes (NAG-1, ATF3, p21, and DDIT3) and performed RT-PCR using gene-specific primers. Among the treated solvent fractions, KSD-E1-3 dramatically induced the expressions of the four selected genes. In addition, we investigated whether the upregulations of those genes were dependent on the transcription factor p53's presence using p53 null HCT116 cells. The results indicate that the upregulations of NAG-1, ATF3, and DDIT3 are not dependent on the p53 presence, whereas p21 is dependent on the p53 presence. These findings may help to understand the molecular mechanisms of the anti-proliferative activity mediated by rice wine lees in human colorectal cancer cells.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.658-666
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• 2021

Podophyllotoxin (PT), a lignan compound from the roots and rhizomes of Podophyllum peltatum, has diverse pharmacological activities including anticancer effect in several types of cancer. The molecular mechanism of the anticancer effects of PT on colorectal cancer cells has not been reported yet. In this study, we sought to evaluate the anticancer effect of PT on human colorectal cancer HCT116 cells and identify the detailed molecular mechanism. PT inhibited the growth of cells and colony formation in a concentration-dependent manner and induced apoptosis as determined by the annexin V/7-aminoactinomycin D double staining assay. PT-induced apoptosis was accompanied by cell cycle arrest in the G2/M phase and an increase in the generation of reactive oxygen species (ROS). The effects of PT on the induction of ROS and apoptosis were prevented by pretreatment with N-acetyl-L-cysteine (NAC), indicating that an increase in ROS generation mediates the apoptosis of HCT116 cells induced by PT. Furthermore, Western blot analysis showed that PT upregulated the level of phospho (p)-p38 mitogen-activated protein kinase (MAPK). The treatment of SB203580, a p38 inhibitor, strongly prevented the apoptosis induced by PT, suggesting that PT-induced apoptosis involved the p38 MAPK signaling pathway. In addition, PT induced the loss of mitochondrial membrane potential and multi-caspase activation. The results suggested that PT induced cell cycle arrest in the G2/M phase and apoptosis through the p38 MAPK signaling pathway by upregulating ROS in HCT116 cells.

• Nutrition Research and Practice
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• v.16 no.2
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• pp.161-172
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• 2022

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness. MATERIALS/METHODS: CD133⁺CD44⁺ HCT116 and CD133⁺CD44⁺ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133⁺CD44⁺ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors. RESULTS: BC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and β-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133⁺CD44⁺ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed in vivo as well. CONCLUSIONS: These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.

• Korean Journal of Food Science and Technology
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• v.44 no.3
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• pp.356-361
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• 2012

Caffeine is a xanthine alkaloid derivative found in many foods and beverages. Dietary caffeine may interact with commonly-consumed over-the-counter (OTC) drugs in body. In this study, cytotoxic effects on the intestinal cells by combined treatment of caffeine with several OTC drugs, including ibuprofen, aspirin, and acetaminophen. Cytotoxic effect of caffeine was more potent in normal intestinal INT 407 cells than in colon cancer HCT 116 cells. Relative toxicity of caffeine and the OTC drugs was significantly enhanced in INT 407 cells when treated together. Intracellular thiol levels of the cells treated with the OTC drugs increased in the presence of caffeine. When HCT 116 cells were incubated with each OTC drug after or before caffeine treatment, the relative cytotoxicity of the OTC drugs increased. The present study may provide basic information about possible health effects through the interactions between caffeine and OTC drugs in the intestinal cells.

• Journal of Korea Entertainment Industry Association
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• v.13 no.1
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• pp.217-223
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• 2019

Colon cancer is the most common form of cancer diagnosis in worldwide. There are growing interests in the health benefits associated with consumption of fruits and vegetables, especially for the prevention of cancer, cardiovascular or other chronic diseases. The objective of the present study was to investigate the antioxidant and anticancer activities of natural product, guarana(GR) and graviola(GV) in human colon carcinoma HCT-116 cells. MTT assay, flow cytometry analysis were employed to investigate the anticancer mechanism and DPPH assay was determined to the antioxidant activity to scavenge free radicals in extract of these. All two extracts showed significantly antioxidant activity at 50mg/ml of concentration. GR and GV reduced HCT-116 cell proliferation in a dose dependent manner. Specially GR treatment(96.65±3.71) also significantly increased the sub-G1 population more than GV(79.58±2.87) treatment in HCT-116 at the concentration of 10mg/ml, as shown by flow cytometry assay. Statistical analyses revealed GR and GV exhibited significantly high (P < 0.05) cytotoxicity in HCT-116. These findings indicate that GN and GV may serve as novel therapeutic agents for colon cancer treatment and future leads for drug development.