Biomedical subjects

I Saiki

Publications and source records attributed to I Saiki.

At least 55 records · Page 3Linked to original sources

PubMed1999

1,3-Selenazine derivatives induce cytotoxicity and DNA fragmentation in human HT-1080 fibrosarcoma cells.

The inhibitory effects of a series of 5,6-dihydro-4H-1,3-selenazine derivatives, 1,3-selenazole, and 5,6-dihydro-4H-1,3-thiazine derivatives on the proliferation of human HT-1080 fibrosarcoma cells were investigated. The compounds 4-ethyl-4-hydroxy-2-p-tolyl-5, 6-dihydro-4H-1,3-selenazine (TS-2) and 4-hydroxy-4-methyl-6-propyl-2-p-tolyl-5,6-dihydro-4H-1,3-selenazine++ + (TS-6) exhibited the strongest inhibitory effect among 1, 3-selenazine derivatives, and the EC(50) of TS-2 and TS-6 was 7.76 and 8.40 microM, respectively. On the other hand, 1,3-selenazole and 5,6-dihydro-4H-1,3-thiazines had no inhibitory effects. TS-2 and TS-6 inhibited the proliferation of HT-1080 cells time- and dose-dependently. They induced dose-dependent DNA fragmentation in HT-1080 cells, revealing a typical apoptosis characteristics. The present study demonstrated that TS-2 and TS-6 inhibited HT-1080 proliferation through the induction of DNA fragmentation.

Apoptosis↗

PubMed1999

Inhibition by vasoactive intestinal polypeptide (VIP) of angiogenesis induced by murine Colon 26-L5 carcinoma cells metastasized in liver.

We investigated the effect of VIP on the liver metastases and angiogenesis by Colon 26-L5 carcinoma cells in mice. Daily systemic administration of VIP, beginning 3 days after tumor inoculation into a portal vein of mice, inhibited significantly the development of their liver metastases. Immunohistochemical staining for factor VIII-related antigen in the sections of liver metastases showed that the systemic administration of VIP caused significant prevention of angiogenesis within tumor masses. VIP (10-(10) to 10(-6) M) inhibited the invasion of reconstituted basement membrane (Matrigel) by hepatic sinusoidal endothelial (HSE) cells in a concentration-dependent manner in a Transwell chamber assay in vitro and achieved approximately 50% reduction of control at 10(-6) M. VIP (10(-6) M) also significantly suppressed the haptotactic migration of HSE cells to fibronectin, laminin or type I collagen substrates with a similar inhibition rate to the invasion assay. Exposure of VIP to HSE cells induced accumulation of intracellular cAMP in a concentration-dependent manner. The inhibitory effect of VIP (10(-6) M) on HSE cell migration was significantly abrogated in the presence of 3 x 10(-6) M H-89, a cAMP-dependent protein kinase inhibitor. VIP (10(-6) M) inhibited the morphogenesis of HSE cells into capillary-like structures on Matrigel-coated wells. VIP did not affect the proliferation of HSE cells and the production of gelatinases in HSE cells in vitro at the concentrations used in the invasion assay. These observations suggest that the anti-metastatic effect of VIP on liver metastases by Colon 26-L5 carcinoma cells in mice is partly due to the prevention of tumor angiogenesis probably through suppression of the motility of endothelial cells.

Animals↗

PubMed1999

Mediastinal lymph node metastasis model by orthotopic intrapulmonary implantation of Lewis lung carcinoma cells in mice.

This study is designed to establish a pulmonary tumour model to investigate the biology and therapy of lung cancer in mice. Current methods for forming a solitary intrapulmonary nodule and subsequent metastasis to mediastinal lymph nodes are not well defined. Lewis lung carcinoma (LLC) cell suspensions were orthotopically introduced into the lung parenchyma of C57/BL6 mice via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. The implantation process was performed within approximately 50 s per mouse, and the operative mortality was less than 5%. Single pulmonary nodules developed at the implanted site in 93% of animals and subsequent mediastinal lymph node metastasis was observed in all mice that formed a lung nodule after intrapulmonary implantation. The size of tumour nodule and the weight of mediastinal lymph node increased in a time-dependent manner. The mean survival time of mice implanted successfully with LLC cells was 21+/-2 days (range 19-24 days). Histopathological analysis revealed that no metastatic tumour was detectable in the mediastinal lymph nodes on day 11, but metastatic foci at mediastinal lymph nodes were clearly observed on days 17 and 21 after implantation. Other metastases in distant organs or lymph nodes were not observed at 21 days after the implantation. Comparative studies with intrapleural and intravenous injections of LLC cells suggest that the mediastinal lymph node metastasis by intrapulmonary implantation is due to the release of tumour cells from the primary nodule, and not due to extrapulmonary leakage of cells. An intravenous administration of cis-diamine dichloro platinum on day 1 after tumour implantation tended to suppress the primary tumour nodule and significantly inhibited lymph node metastasis. Thus, a solitary pulmonary tumour nodule model with lymph node metastasis approximates clinical lung cancer and may provide a useful basis for lung cancer research.

Animals↗

PubMed1999

Invasiveness of hepatocellular carcinoma cell lines: contribution of membrane-type 1 matrix metalloproteinase.

Intrahepatic metastasis is one of the malignant features of hepatocellular carcinoma (HCC). Matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (u-PA)/plasmin, are known to be associated with the invasive properties of various types of tumor cells. In this study, we examined which proteinases play a role in the metastatic invasion of human HCC cell lines. JHH-5 and JHH-6 cells constitutively expressed mRNAs for both membrane-type 1 matrix metalloproteinase (MT1-MMP) and u-PA and invaded through reconstituted MATRIGEL in vitro, whereas JHH-7 cells expressed u-PA mRNA but not MT1-MMP and did not invade. However, hepatocyte growth factor (HGF) induced MT1-MMP expression on the surface of JHH-7 cells and markedly increased invasiveness of JHH-7 in a concentration-dependent manner. Moreover, cleavage activity for pro-MMP-2 was induced in HGF-treated JHH-7 cells. MMP inhibitor, rather than serine proteinase inhibitor, potently inhibited HCC cell invasion. Intrahepatic injection of HCC cell lines into athymic nude mice caused visible intrahepatic metastases in vivo. Moreover, JHH-7 tumors showed expression of MT1-MMP mRNA, while in vitro cultured JHH-7 cells did not. These findings suggest that MT1-MMP plays an important role in the invasive properties of HCC cells, and that HGF modifies the invasive properties of noninvasive HCC cells.

Animals↗

PubMed1999

TAC-101 (4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid) inhibits spontaneous mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma.

The anti-tumor and anti-metastatic effects of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid (TAC-101) were investigated using our established lung cancer model. Orthotopic implantation of Lewis lung carcinoma (LLC) cells into the lung parenchyma produced a solitary tumor nodule in the lung followed by mediastinal lymph node metastasis. Daily oral administration of TAC-101 at doses ranging from 4 to 16 mg/kg resulted in a significant inhibition of lymphatic metastasis (inhibition rate=57 to 76%), while only the dose of 16 mg/kg significantly inhibited tumor growth at the implanted sites (inhibition rate=46%). Combined treatment with cis-diamminedichloroplatinum (CDDP) and TAC-101 (8 mg/kg, p.o., daily) enhanced the anti-tumor effect of CDDP (7 mg/kg, i.v., bolus) against both the growth of implanted tumor and lymphatic metastasis. In addition, this combined treatment significantly prolonged the survival time of LLC tumor-bearing mice as compared to treatment with each agent alone. The anti-activating protein-1 (AP-1) activity of TAC-101 caused inhibition of LLC cell invasion through the repression of expression of urokinase-type plasminogen activator and its receptor. The anti-invasive activity of TAC-101 may be involved in its in vivo anti-metastatic activity. These findings suggest that TAC-101 is a novel anti-cancer agent that may improve the therapeutic modalities for lung cancer patients with metastatic disease.

Angiogenesis Inhibitors↗

PubMed1999

Role of Th1 and Th2 cytokines in regulating the liver injury induced by delayed-type hypersensitivity to picryl chloride.

AIMS/BACKGROUND: We have previously reported that a new model of liver injury induced in mice by delayed-type hypersensitivity (DTH) to picryl chloride (PCl) mimicks the pathogenesis of human hepatitis. This liver injury is mediated by CD4+ T cells. The interaction between lymphocyte function associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) is an essential process for hepatocyte (HC) damage. The present study was undertaken to reveal the role of Th1 and Th2-like cytokines in regulating the liver injury. METHODS: The kinetics of cytokine production were examined by ELISA and RT-PCR after the elicitation of liver injury for both serum protein and liver mRNA expression, respectively. A co-culture assay between liver nonparenchymal cells (NPC) and HC was conducted to evaluate the cytokine regulation on the cell-cell interaction. Expression of LFA-1 on NPC and ICAM-1 on HC were examined by FACScan and ELISA, respectively. RESULTS: Serum IL-2 and IFN-gamma showed a peak production at 6 and 12 h, while IL-5 and IL-4 reached their maximum levels at 18 and 24 h after induction of liver injury, respectively. Liver mRNA expression of IFN-gamma and IL-4 had a similar time course to their corresponding products. Both recombinant murine IFN-gamma and IL-2 triggered the hepatotoxicity of NPC or spleen cells at 0 h. In this case, an increased expression of both LFA-1 on NPC and ICAM-1 on HC was also observed. In contrast, IL-4 and IL-5 completely abolished the hepatotoxicity of NPC at 12 h without influencing the adhesion molecules. CONCLUSION: Th1 and Th2 may be involved in regulating liver injury. Th1/Th2 balance may critically contribute to the production of the liver injury or recovery from it.

Animals↗

PubMed1999

Inhibitory mechanisms of glycoprotein fraction derived from Miscanthus sinensis for the immediate phase response of an IgE-mediated cutaneous reaction.

We investigated the inhibitory effect of the glycoprotein fraction (fraction 2) extracted from Miscanthus sinensi ANDERSSON (M. sinensis) on biphasic cutaneous reactions in mice passively sensitized with IgE. Biphasic skin reactions with peak responses at 1 (IPR, immediate phase reaction) and 24 h (LPR, late phase reaction) were caused by passive sensitization with an anti-dinitrophenol IgE monoclonal antibody (anti-DNP IgE mAb) followed by an epicutaneous challenge of 0.1% dinitrofluorobenzene (DNFB) in 100% ethanol. Intraperitoneal injection of fraction 2 before the DNFB challenge significantly inhibited the biphasic ear swelling response in passively sensitized mice in a dose-dependent manner (1-30 mg/kg). We also found that fraction 2 was effective at inhibiting the vascular permeability in mouse ear induced by an injection of compound 48/80, histamine or serotonin. In addition, fraction 2 inhibited scratching behavior as well as ear edema observed within 2 h after DNFB challenge. Marked inhibition was observed in both passively sensitized and non-sensitized mice. The locomotor activity of mice was also reduced by the administration of fraction 2 as well as by diphenhydramine. These results suggest that the inhibitory effect of glycoprotein fraction 2 of M. sinensis on an IgE-mediated allergic inflammatory reaction is due to the protection of mediator-induced vascular permeability and that in addition to the inhibition of an inflammatory reaction, a sedative action is responsible for the inhibition of allergy-induced scratching responses.

Acute-Phase Reaction↗

PubMed1999

HPLC analysis of juzen-taiho-to and its variant formulations and their antimetastatic efficacies.

Our previous study demonstrated that the oral administration of Juzen-taiho-to resulted in a significant inhibition of the liver metastasis of colon 26-L5 cells as compared with the untreated control, without side effects. We attempted to investigate the relationship between the HPLC pattern (referred to as the fingerprint) of the formulation and its component crude drugs and the inhibition of tumor metastasis in order to obtain the optimal efficacy and constant quality of the formulation. Two Juzen-taiho-to formulations (batches #1 and #2), which were individually prepared using the same 10 crude drugs and the same preparation procedure, showed similar anti-metastatic effects and absorbance patterns by HPLC analysis. Some variant formulations of Juzen-taiho-to, in which one crude drug was substituted with other crude drugs from different sources or places of origin, exhibited reduced efficacy as compared with the original formulation, as well as differences in the fingerprint pattern compared with the original formulation. Juzen (Naimo-Ogi-->Kibana-Ogi), a variant formulation with the substitution of Astragali radix of a different origin and place of harvest, showed significant inhibition of the liver metastasis of tumor cells and a HPLC fingerprint pattern similar to that of the original formulation. Thus, HPLC fingerprint analysis of Kampo medicines may provide a useful basis for obtaining their optimal efficacy as well as constant quality of the formulation, although it has some problems and limitations, such as detectability by and sensitivity to UV absorbance.

Animals↗

PubMed1999

[Tumor metastasis and cell adhesion molecules].

The adhesive interaction between tumor cells, host cells or extracellular matrix (ECM) plays a crucial role in metastatic formation. We used synthetic polypeptide containing a repetitive core sequence, Arg-Gly-Asp (RGD), of cell-adhesive molecules; poly (RGD), to antagonize the adhesive interaction between ECM and integrin receptors on tumor cell surface during the metastatic cascade. Poly (RGD) significantly inhibited the experimental lung and liver metastasis as compared with RGD peptide when it was coinjected i.v. with different types of tumors. In a spontaneous lung metastasis model using B16-BL6 melanoma, multiple i.v. administrations of poly (RGD), before or after surgical excision of the primary tumor, resulted in significant reduction of the lung colonization. The mechanism responsible for the inhibition is partly associated with the ability to interfere with cell functions such as adhesiveness, motility, and invasiveness in the metastatic process. Poly (RGD) showed no cytotoxicity against host and tumor cells. Thus, the regulation of adhesive interaction of tumor cells with ECM or host cells by anti-adhesive polypeptides may provide a promising approach for the prevention of tumor metastasis.

Animals↗

PubMed1999

Inhibition of angiogenesis and intrahepatic growth of colon cancer by TAC-101.

We demonstrated in this study that inhibition of intra-hepatic growth of colon cancer by TAC-101 is mediated by inhibition of angiogenesis. In vitro experiments showed that TAC-101 inhibited the proliferation of murine hepatic sinusoidal endothelial (HSE) cells induced by coculture with murine colon 26-L5 (L5) cells. HSE cell proliferation was also enhanced by conditioned medium of L5 cells (CM-L5), and this enhancement of proliferation was abrogated by anti-vascular endothelial growth factor antibody. CM-L5 also induced in vitro tube formation of HSE cells on Matri-gel, and this activity of CM-L5 was abrogated by TAC-101 in a concentration-dependent manner. On the other hand, p.o. administration of TAC-101 inhibited tumor-induced angiogenesis in vivo and decreased the weights of L5 tumors in the mouse liver. Reverse transcriptase-PCR analysis using in vivo tumor tissue suggested that repression of vascular endothelial growth factor expression by TAC-101 was associated with the antiangiogenic activity. TAC-101 alone and 5-fluorouracil (5-FU)/D,L-leucovorin (LV) significantly inhibited the intrahepatic growth of L5 tumors (P = 0.002 and 0.001, respectively), whereas 5-FU alone did not (P = 0.088). When TAC-101 was administered with 5-FU/LV, marked enhancement of antitumor activity was observed (95% inhibition; P<0.001). This enhanced antitumor effect was also observed in experiments using Co-3 human colon adenocarcinoma. Concurrent treatment with TAC-101 and 5-FU/LV and sequential treatment with 5-FU/LV followed by TAC-101 resulted in significant augmentation of antitumor activity against Co-3 (overall P = 0.007 and 0.015, respectively). These findings indicate that TAC-101 inhibits tumor angiogenesis and suggest that it may be effective against hepatic metastasis of colon cancer.

Adenocarcinoma↗

PubMed1999

Model for mediastinal lymph node metastasis produced by orthotopic intrapulmonary implantation of lung cancer cells in mice.

This study is designed to establish a pulmonary tumor model to investigate the biology and therapy of lung cancer in mice. Current methods for forming a solitary intrapulmonary nodule and subsequent metastasis to mediastinal lymph nodes are not well defined. Lewis lung carcinoma cell (LLC) suspensions were orthotopically introduced into the lung parenchyma of C57/BL6 mice via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. The implantation process was performed within approximately 50 sec per mouse, and the operative mortality was less than 5%. Single pulmonary nodules developed at the implanted site in 93% of animals and subsequent mediastinal lymph nodes metastasis were observed in all mice that were succeeded to form a lung nodule after intrapulmonary implantation. The size of tumor nodule and the weight of mediastinal lymph node increased in a time-dependent manner. The mean survival time of mice implanted successfully with LLC cells was 21 +/- 2 days (range; 19-24 days). Histopathological analysis revealed that no metastatic tumor was detectable in the mediastinal lymph nodes on day 11, but metastatic foci at mediastinal lymph nodes were clearly observed on days 17 and 21 after implantation. Other metastases in distant organs or lymph nodes were not observed at 21 days after the implantation. Comparative studies with intrapleural and intravenous injections of LLC cells suggest that the mediastinal lymph node metastasis by intrapulmonary implantation is due to the release of tumor cells from the primary nodule, and not due to extrapulmonary leakage of cells. An intravenous administration of CDDP on day 1 after tumor implantation tended to suppress the primary tumor nodule and significantly inhibited the lymph node metastasis. Thus, a solitary pulmonary tumor nodule model with lymph node metastasis approximates clinical lung cancer, and may provide a useful basis for lung cancer research.

Animals↗

PubMed1999

Involvement of TNF-alpha in enhancement of invasion and metastasis of colon 26-L5 carcinoma cells in mice by social isolation stress.

Psychosocial stress has been implicated in tumor metastasis. We have previously reported that social isolation stress exacerbated liver metastasis of colon 26-L5 by partially suppressing the cellular immunity in male Balb/c mice. To further understand the mechanism underlying the influence of isolation stress on liver metastasis, we investigated the effect of social isolation stress on tumor invasion, which is considered to be a pivotal step of tumor metastasis. The invasion and migration of tumor cells obtained from tumor nodules in the isolated mice were more markedly enhanced than that in the group-housed mice. The mRNA expression of proteolytic proteases, including matrix metalloproteinase (MMP)-2, MMP-9, membrane type 1 (MTI)-MMP, and urokinase-type plasminogen activator (u-PA), were increased in the tumor and liver tissues of the isolated mice compared with the control mice. On the other hand, production of plasma TNF-alpha and expression of hepatic TNF-alpha mRNA were elevated in the isolated mice with or without tumor burden. Increased TNF-alpha level was particularly discernible in the liver of tumor-bearing mice. Elevated positive staining for TNF-alpha was immunohistochemically observed within and around tumor mass in the liver from isolated tumor-bearing mice, compared with group-housed mice. In addition, the invasiveness of tumor cells and the expression of proteolytic enzymes, including MMP-9 and u-PA in tumor cells, were enhanced by the treatment of TNF-alpha in vitro. Thus, the data suggested that isolation stress-augmented TNF-alpha may be involved in the enhancement of tumor invasion and metastasis in part by upregulating the proteolytic enzymes such as MMPs and u-PA in tumor and liver tissues.

Animals↗

PubMed1998

Cytotoxic cycloartane-type triterpenes from Combretum quadrangulare.

Seven novel cycloartane-type triterpenes were isolated from Combretum quadrangulare, and their structures were elucidated on the basis of spectral analysis. All these compounds were tested for their cytotoxicity against murine colon 26-L5 carcinoma cells. Methyl quadrangularate B (2) and methyl quadrangularate D (4) exhibited potent cytotoxicity having ED50 values 9.54 and 5.42 microM, respectively.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Effect of prostatic neuropeptides on invasion and migration of PC-3 prostate cancer cells.

We investigated the effect of various neuropeptides present in the prostate, including calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), glucagon and parathyroid hormone-related protein (PTH-rP), on the invasion of PC-3 prostate cancer cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. Both CGRP and GRP increased the invasive capacity of tumor cells, whereas SP inhibited it. On the other hand, VIP, CT, L-ENK, NPY, glucagon and PTH-rP had no significant effect. Both CGRP and GRP also increased the haptotactic migration of tumor cells to fibronectin, but SP inhibited it. These three neuropeptides had no effect on either adhesion to fibronectin and laminin or on the gelatinolytic activities of MMP-9 in gelatin zymography, nor did they affect the growth of tumor cells at concentrations used in this study. These results indicate that both GRP and CGRP increased the invasive potential of PC-3 cells probably through enhancement of cell motility, while SP inhibited the invasiveness through suppression of motile response.

Calcitonin Gene-Related Peptide↗

PubMed1998

An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells.

Our previous study demonstrated that the in vivo anti-metastatic effect induced by oral administration of ginseng protopanaxadiol saponins was mediated by their metabolic component M1, and that the growth, invasion and migration of tumor cells were inhibited by M1 but not by ginsenosides. Here we investigated the inhibitory mechanism of M1 on the growth of tumor cells. M1 inhibited the proliferation of B16-BL6 mouse melanoma cells in a time- and dose-dependent manner, with accompanying morphological changes at the concentration of 20 microM. In addition, at 40 microM M1 induced apoptotic cell death within 24 h. Fluorescence microscopy revealed that dansyl M1 entered the cytosol and quickly reached the nuclei (approximately 15 min). Western blot analysis revealed that M1 rapidly up-regulated the expression of p27Kip1, but down-regulated the expression of c-Myc and cyclin D1 in a time-dependent manner. Thus, the regulation of apoptosis-related proteins by M1 is responsible for the induction of apoptotic cell death, and this probably leads to the anti-metastatic activity in vivo.

Animals↗

PubMed1998

A new pseudo-peptide analogue of the Arg-Gly-Asp (RGD) sequence inhibits liver metastasis of colon 26-L5 carcinoma cells.

We have investigated the effect of the pseudo-peptide analogue (FC-336) of the Arg-Gly-Asp (RGD) sequence in a liver metastasis model by the inoculation of a highly liver-metastatic cell line of colon 26 carcinoma (colon 26-L5) into the portal vein of BALB/c mice. The intraportal injection of colon 26-L5 cells with FC-336 resulted in a marked suppression of liver metastatic colonies in a dose-dependent manner and it reduced the liver weights to a normal level. However, the co-injection of tumor cells with a high dose of RGDS tetrapeptide led to a slight inhibition of liver metastasis. The multiple i.v. administration of FC-336 after tumor inoculation as well as the injection of FC-336 with tumor cells caused significant inhibition of experimental metastasis in the liver. The multiple i.v. administration of the RGDS peptide did not show any inhibitory activity. FC-336 significantly enhanced the survival rate of mice compared with untreated controls when injected intraportally with tumor cells or when intravenously administered after tumor inoculation. Zymography analysis showed that FC-336 inhibited the degradation of gelatin substrate by matrix metalloproteinases (MMPs) produced by colon 26-L5 cells, while RGDS peptide did not affect the enzymatic degradation. These findings clearly indicate that the pseudo-peptides of the RGD sequence (FC-336) have a potent inhibitory activity on liver metastasis of colon 26-L5 carcinoma cells.

Animals↗

PubMed1998

LEA-1/ICAM-1 interaction is essentially involved in the pathogenesis of delayed-type hypersensitivity-induced liver injury to picryl chloride.

The kinetics of lymphocyte function associated antigen 1 (LFA-1) expression on spleen cells (SPC) and liver non-parenchymal cells (NPC), and intercellular adhesion molecule 1 (ICAM-1) expression on hepatocytes (HC) was examined in acute liver injury mice induced by a DTH reaction to picryl chloride (PCl). The peak expression of LFA-1 on SPC was seen at 6 hr after eliciting liver injury, and then that of LFA-1 on NPC and ICAM-1 on HC appeared at 12 hr. Thereafter, the serum ALT elevation reached to a peak at 18 hr. A splenectomy before the PCl elicitation significantly reduced the ALT elevation. Both SPC and NPC from liver injury mice induced a remarkable release of ALT from HC in vitro, in parallel with their LFA-1 expression. The pre-treatment of NPC or SPC with anti-LFA-1 mAb, irrespective of the presence of complement, completely blocked the ALT release. Also, when HC was prebound with anti-ICAM-1 mAb, neither NPC nor SPC showed a cytotoxicity against the HC. Furthermore, the treatment of NPC with either anti-Thy1.2 or anti-CD4 mAb in the presence but not absence of complement, showed a complete abolishment of ALT release. Anti-CD8 mAb plus complement also tended to inhibit ALT release. The twofold increase in CD4+ LFA-1+ and mild increase in CD8+ LFA-1+ populations were also confirmed in NPC at 12 hr. These results suggest that PCl elicitation in liver may trigger an increased expression of LFA-1 on SPC and NPC and ICAM-1 on HC. LFA-1/ICAM-1 interaction between liver-infiltrating NPC, mainly including CD4+ and CD8+ T cells, and HC may be an essential step for the hepatocyte damage in PCl-DTH liver injury.

Alanine Transaminase↗

PubMed1998

Chemical constituents of Brazilian propolis and their cytotoxic activities.

The EtOAc-soluble fraction of the MeOH extract of propolis afforded a new prenylated chromane derivative, 3-hydroxy-2, 2-dimethyl-8-prenylchromane-6-propenoic acid (1), along with 22 known compounds, 2-23. Of the known compounds, 4, 7, 12-19, and 22 were isolated for the first time from propolis, and the absolute configuration of 23 was established as (2S,3R). Investigation suggested that Baccharis spp. are a significant source of tropical Brazilian propolis, in addition to Clusia minor, Clusia major, and Araucaria heterophylla. All the compounds were tested for their cytotoxicity toward human HT-1080 fibrosarcoma and murine colon 26-L5 carcinoma cells. Among these compounds, 9 and 19-21 showed potent cytotoxicity, having ED50 values equal to or less than 10 microg/mL.

Animals↗