• Oncology Letters
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• v.18 no.6
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• pp.5889-5896
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• 2019

The elimination of residual microscopic cancer cells is important cancer treatment. The immunoediting theory describes the balance between the immune system and cancer cells. The current study investigated changes in the immune system during the elimination of cancer cells and evaluated the influence of cluster of differentiation (CD)4 or CD8 depletion. A human squamous cell cancer cell line (SNU1041) was injected in the lateral tongue of immunocompetent mice and the changes in the CD4, CD8, CD11b, CD19, CD40 and CD40 ligand (L) populations in the blood, lymph nodes and spleen were evaluated using flow cytometry, and changes in serum cytokine levels were evaluated using a magnetic bead panel. Cancer cell elimination was delayed by CD4 depletion but not by CD8 depletion. The CD8-depleted group indicated increased levels of CD40L, interferon-gamma, interleukin (IL)-10, IL-6, and tumor necrosis factor-α. It was concluded that CD4 served a crucial role in the elimination of human cancer cells. Furthermore, the efficacies of CD40 agonist and programmed cell death protein 1 (PD1) antagonist treatments were assessed in CD4-depleted mice. CD40 agonist treatment resulted in faster cancer cell elimination and increased cytokine excretion. In conclusion, CD4 or CD40L significantly influenced cancer elimination. CD40 agonist antibodies may be potent adjuvant agents that can be used in patients with reduced CD4 or CD40L expression

• Journal of dental hygiene science
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• v.7 no.1
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• pp.31-35
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• 2007

Caesalpinia sappan L. (Leguminosae) is an oriental medicinal herb distributed in China and Taiwan, and its heartwood has been traditionally used as an analgesic, a therapy for thrombosis or tumor. This study was to investigate the proliferation and inhibition effects of Caesalpinia sappan extracts against human epithelial cell and cancer cell lines. The methanol extract of dried C. sappan heartwood was evaporated (KS-6), and then sequentially extracted by hexane (KS-01), chloroform (KS-02), ethyl acetate (KS-03), n-butanol (KS-04), and water (KS-05). After 48 hr of exposure, these fractions at a concentration of $50{\mu}g/ml$ significantly increased, and reduced cell proliferation in both human normal epithelial and cancer cell lines. The ethyl acetate fraction (KS-03) among organic solvent fractions was 120.2% of the most proliferation activity ($50{\mu}g/ml$) against HaCaT human epithelial cell. However, fractions from chloroform, butanolic and methanolic extract had 7.2, 28.7 and 20.8% of antiproliferative effect on HaCaT cell, respectively. In cell proliferation effects of C. sappan extract on HeLa, SiHa and C33A human cervical cancer cells, chloroform fraction (KS-2) was the most antiproliferative activity, its antiproliferative rate (dosage, $50{\mu}g/ml$) relative to control was 25.8, 12.2 and 17.4% for SiHa, HeLa and C33A, respectively. The results indicated that the six extract fractions could induce cell cycle stimulate or arrest in some way. Finally, further investigation is needed to assess the molecular mechanisms mediated anticancer activities of this plant.

• Korean Journal of Plant Resources
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• v.30 no.3
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• pp.265-271
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• 2017

In this study, we elucidated the molecular mechanism of silymarin by which silymarin may inhibits cell proliferation in human colorectal cancer cells in order to search the new potential anti-cancer target associated with the cell growth arrest. Silymarin reduced the level of c-Myc protein but not mRNA level indicating that silymarin-mediated downregulation of c-Myc may result from the proteasomal degradation. In the confirmation of silymarin-mediated c-Myc degradation, MG132 as a proteasome inhibitor attenuated c-Myc degradation by silymarin. In addition, silymarin phosphorylated the threonine-58 (Thr58) of c-Myc and the point mutation of Thr58 to alanine blocked its degradation by silymarin, which indicates that Thr58 phosphorylation may be an important modification for silymarin-mediated c-Myc degradation. We observed that the inhibition of ERK1/2, p38 and $GSK3{\beta}$ blocked the Thr58 phosphorylation and subsequent c-Myc degradation by silymarin. Finally, the point mutation of Thr58 to alanine attenuated silymarin-mediated inhibition of the cell growth. The results suggest that silymarin induces the cell growth arrest through c-Myc proteasomal degradation via ERK1/2, p38 and $GSK3{\beta}-dependent$ Thr58 phosphorylation.

• Journal of Radiation Industry
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• v.9 no.4
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• pp.187-192
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• 2015

CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrix interactions. In particular, splice variants of CD44 are particularly overexpressed in a large number of malignancies and carcinomas. In this study, the $^{177}Lu$-labelled CD44 targeting antibody was prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with the equivalent molar ratio of cysteine-based DTPA-NCS and radioimmunoconjugated with $^{177}Lu$ at room temperature within 15 minutes. The stability was tested in human serum. An in vitro study was carried out in HT-29 human colon cancer cell lines. For the biodistribution study $^{177}Lu$-labelled anti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteine-based DTPA-NCS and purified by a centricon filter system having a molecular cut-off of 50 kDa. Radioimmunoconjugation with $^{177}Lu$ was reacted for 15 min at room temperature. The radiolabeling yield was >99%, and it was stable in human serum without any fragmentation or degradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cell surfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was 43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. The anti-CD44 monoclonal antibody for the targeting of colon cancer was effectively radioimmunoconjugated with $^{177}Lu$. The in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell binding assay. In addition, the antibody's tumor targeting ability was demonstrated with very high uptake in tumors. This radioimmunoconjugate is applicable to therapy in human colon cancer with highly expressed CD44.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6541-6548
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• 2013

Pigmented rice is mainly black, red, and dark purple, and contains a variety of flavones, tannin, polyphenols, sterols, tocopherols, ${\gamma}$-oryzanols, amino acids, and essential oils. The present study evaluated the cytotoxic effects of purple rice extracts (PREs) combined with chemotherapeutic drugs on human cancer cells and mechanisms of cell death. Methanolic (MeOH) and dichloromethane (DCM) extracts of three cultivars of purple rice in Thailand: Doisaket (DSK), Nan and Payao (PYO), were tested and compared with white rice (KK6). Cytotoxicity was determined by 3-(4, 5-dimethyl)-2, 5-diphenyltetrazolium bromide (MTT) assay in human hepatocellular carcinoma HepG2, prostate cancer LNCaP and murine normal fibroblast NIH3T3 cells. MeOH-PYO-PRE was the most cytotoxic and inhibited HepG2 cell growth more than that of LNCaP cells but was not toxic to NIH3T3 cells. When PREs were combined with paclitaxel or vinblastine, they showed additive cytotoxic effects on HepG2 and LNCaP cells, except for MeOH-PYO-PRE which showed synergistic effects on HepG2 cells when combined with vinblastine. MeOH-PYO-PRE plus vinblastine induced HepG2 cell apoptosis with loss of mitochondrial transmembrane potential (MTP) but no ROS production. MeOH-PYO-PRE-treated HepG2 cells underwent apoptosis via caspase-9 and-3 activation. The level of ${\gamma}$-oryzanol was highest in DCM-PYO-PRE (44.17 mg/g) whereas anthocyanin content was high in MeOH-PYO-PRE (5.80 mg/g). In conclusion, methanolic Payao purple rice extract was mostly toxic to human HepG2 cells and synergistically enhanced the cytotoxicity of vinblastine. Human HepG2 cell apoptosis induced by MeOH-PYO-PRE and vinblastine was mediated through a mitochondrial pathway.

• Journal of Nutrition and Health
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• v.39 no.4
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• pp.347-356
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• 2006

It is reported that a fermented soybean food, Doenjang, has srong antimutagenic and cytotoxic effect on cancer cells. This study investigated the effect of Chungkookjang, another traditional popular Korean soybean fermented food, on growth of cancer cells: HL-60, SNU-638 and MCF-7, and also its in vivo antitumorigenic effect in DMBA-induced mammary tumor rat model. For the in vitro study, Chungkookjang and steamed soybeans were extracted with ethanol and sequentially fractioned with 5 kinds of solvents differing in grades of polarity such as hexane, dichloromethane, ethylacetate, butanol and water. Almost all Chungkookjang extracts significantly inhibited the growth of HL-60 (human leukemic cancer cell), SNU-638 (human gastric cancer cell) and MCF-7 (human breast cancer cell) when compared to steamed soybean extracts. Butanol fraction of Chungkookjang extract especially showed a remarkable inhibitory effect in all the three kinds of cancer cells. To induce a mammary gland tumor, DMBA (50 mg/BW) was administered to 50 day-old female rats and followed by Chungkookjang or steamed soybean supplemented diets. Freezedried Chungkookjang powder (20% of diet in wet weight) was added to AIN-93G based diet for the Chungkookjang group of rats. Likewise, steamed soybean powder containing equal protein content to that of Chungkookjang powder was supplemented to soybean group of rats. At 13 weeks later, the mammary tumor incidence, average tumor number and tumor weight a rat were lower in Chungkookjang group compared to the control or soybean group. In conclusion, Chungkookjang showed a strong inhibitory effect on cancer cell growth in vitro, as well as a more preventive effect against chemically induced mammary tumorigenesis in vivo, while steamed soybeans did not. Therefore, these results suggest that Chungkookjang acquire its anticancer activity through the fermentation process.

• YAKHAK HOEJI
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• v.38 no.3
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• pp.311-321
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• 1994

Anticancer effects of Aloe on sarcoma 180 in ICR mouse or human cancer cells were determined. Sarcoma 180 cells were inoculated subcutaneously into male ICR mouse to determine effect of Aloe on tumor gowth, or inoculated intraperitoneally into male ICR mouse to determine effect of Aloe on life span prolongation, followed by oral administration of Aloe vera(10 mg/kg/day, 50 mg/kg/day) or Aloe arborescens(10 mg/kg/day, 100 mg/kg/day) once a day for 14 days. The administration of Aloe vera or Aloe arborescens did not suppress tumor growh. However the life span of ICR mouse was prolonged to 19%(p<0.05), 22%(p<0.05) and 32%(p<0.05) by administration of Aloe vera 10 mg/kg/day, Aloe vera 50 mg/kg/day, and Aloe arborescens 100 mg/kg/day, respectively. To determine anticancer effect of Aloe in vitro, Aloe extract was added to the culture of human gastric cancer cells(SNU-1) and colorectal cancer cells(SNU-C2A), and concentration of Aloe to inhibit cancer cell growth was determined using MTT(3-[ 4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) cytotoxicity assay. High $ID_{50}$ values of Aloe vera and Aloe arborescens against gastric cancer cell line(SNU-1) and colorectal cancer cell line(SNU-C2A) suggest that Aloe gel does not have anticancer effect on these specific human cancer cells although high concentration of Aloe inhibited growth of human cancer cells significantly.

• International Journal of Oral Biology
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• v.32 no.3
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• pp.93-101
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• 2007

Cell behavior of the transformed cells is known to affect by interaction with extracellular matrix (ECM) proteins and integrin. To investigate the alterations of both integrin expression and cell-matrix interaction during neoplastic conversion of human oral kerationcytes, we studied expression levels of integrin subunits by flow cytometry and cellular responses to the ECM proteins in normal human oral keratinocytes (NHOKs), HPV-immortalized HOK-16B line, and three oral cancer cell lines established from HOK-16B line, CTHOK-16B-BaP, CTHOK-16B-DMBA, and CTHOK-16B-Dexa lines. The expression levels of ${\alpha}\;and\;{\beta}$ integrin subunits were shown decreased tendency in human oral keratinocytes undergoing immortalization and tumorigenic transformation except CTHOK-16B-DMBA line tested. Although ${\alpha}v{\beta}6$ integrin is known to be highly expressed in squamous cell carcinomas, and the altered integrin expression is suspected to be associated with cellular carcinogenesis, ${\alpha}v$ integrin subunit and ${\alpha}v{\beta}6$ integrin did not express in oral cancer cell lines tested. Cell behavior to the ECM proteins in HOK-16B line was generally similar to that of exponentially proliferating NHOKs. The adhesion activity profiles of type I collagen were very similar to that of its laminin counterparts, but fibronectin showed minimal adhesion activity under our conditions compared to the BSA control. The ability of the CTHOK-16B-BaP line to spread upon type I collagen and laminin markedly decreased, but migration was notably increased on type I collagen. In contrast, CTHOK-16B-DMBA and CTHOK-16B-Dexa lines spread less but migrated more upon type I collagen than immortalized HOK-16B line. These data indicate that downregulation of integrin subunits causes the changes of cellular responses to the ECM proteins during neoplastic conversion of human oral keratinocytes, and that cellular responses to the ECM proteins in oral cancer cell lines established by exposing different carcinogens are variable according to chemical carcinogens treatment.

• Genomics & Informatics
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• v.21 no.1
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• pp.11.1-11.5
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• 2023

Breast cancer is the most common cancer worldwide, and advanced breast cancer with metastases is incurable mainly with currently available therapies. Therefore, it is essential to understand molecular characteristics during the progression of breast carcinogenesis. Here, we report a dataset of whole genomes from the human mammary epithelial cell system derived from a reduction mammoplasty specimen. This system comprises pre-stasis 184D cells, considered normal, and seven cell lines along cancer progression series that are immortalized or additionally acquired anchorage-independent growth. Our analysis of the whole-genome sequencing (WGS) data indicates that those seven cancer progression series cells have somatic mutations whose number ranges from 8,393 to 39,564 (with an average of 30,591) compared to 184D cells. These WGS data and our mutation analysis will provide helpful information to identify driver mutations and elucidate molecular mechanisms for breast carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2179-2183
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• 2014

Background: In vitro, in vivo and clinical studies have demonstrated anti-cancer effects of deuterium depleted water (DDW). The nature of this agents action, cytotoxic or cytostatic, remains to be elucidated. We here aimed to address the point by examining effects on different cell lines. Materials and Methods: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) -based cytotoxicity analysis was conducted for human breast, stomach, colon, prostate cancer and glioblastoma multiforme cell lines as well as human dermal fibroblasts. The cell lines were treated with decreasing deuterium concentrations of DDW alone, paclitaxel alone and both. One way analysis of variance (ANOVA) was used for statistical analysis. Results: Treatment with different deuterium concentrations of DDW alone did not impose any significant inhibitory effects on growth of cell lines. Paclitaxel significantly decreased the survival fractions of all cell lines. DDW augmented paclitaxel inhibitory effects on breast, prostate, stomach cancer and glioblastoma cell lines, with influence being more pronounced in breast and prostate cases. Conclusions: DDW per se does not appear to have inhibitory effects on the assessed tumor cell lines as well as normal fibroblasts. As an adjuvant, however, DDW augmented inhibitory effects of paclitaxel and thus it could be considered as an adjuvant to conventional anticancer agents in future trials.