γ-Tocotrienol induces paraptosis-like cell death in human colon carcinoma SW620 cells.

Colorectal cancer is one of the most serious illnesses among diagnosed cancer. As a new type of anti-cancer composition from tocotrienol-rich fraction of palm oil, γ-tocotrienol is widely used in anti-cancer research. The objectives of this study were to investigate the effects of γ-tocotrienol on human colon cancer SW620 and HCT-8 cells. We showed that treatment with different concentrations of γ-tocotrienol resulted in a dose dependent inhibition of cell growth. Cell death induced by γ-tocotrienol was mediated by a paraptosis-like cell death in SW620 and HCT-8 cells. Real-time RT-PCR and western blot analyses showed that γ-tocotrienol inhibited the expression level of ß-catenin, cyclin D1 and c-jun. These data suggest that a paraptosis-like cell death induced by γ-tocotrienol in SW620 cells is associated with the suppression of the Wnt signaling pathway, which offers a novel tool for treating apoptosis-resistance colon cancer.

A paraptosis-like cell death induced by δ-tocotrienol in human colon carcinoma SW620 cells is associated with the suppression of the Wnt signaling pathway.

Tocotrienol is considered a beneficial effect agent on inhibition of tumor development. In this study, we focused on the effects of δ-tocotrienol and its possible mechanism on induction of death in human colon cancer SW620 cells. δ-Tocotrienol inhibited proliferation of SW620 cell in a dose-dependent manner. Our findings showed that δ-tocotrienol effectively induced paraptosis-like death in SW620 cells, correlated with the vacuolation that may be from welling and fusion of mitochondria and/or the endoplasmic reticulum (ER) as well as caspase-3 nonactivated. However, there were no changes in apoptosis based on flow cytometry analysis. Of being noted, δ-tocotrienol reduced the expression of ß-catenin and wnt-1 proteins by about 50% at the highest dose (20µmol/L). δ-Tocotrienol also decreased cyclin D1, c-jun and MMP-7 protein levels in SW620 cells. Altogether, these data indicate that δ-tocotrienol induces paraptosis-like cell death, which is associated with the suppression of the Wnt signaling pathway. Thus, our findings may provide a novel application in treatment of human colon carcinoma.

γ-Tocotrienol inhibits angiogenesis of human umbilical vein endothelial cell induced by cancer cell.

Antiangiogenic therapy mediated by food components is an established strategy for cancer chemoprevention. Growth factors play critical roles in tumor angiogenesis. A conditioned medium containing growth factors from human gastric adenocarcinoma SGC-7901 cell conditioned medium was used as an angiogenic stimulus in this study. The purpose of this study was to evaluate the inhibitory effect and possible mechanism of γ-tocotrienol on tumor angiogenesis. The results showed that γ-tocotrienol (10-40 µmol/L) significantly suppressed proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) induced by SGC-7901 cell conditioned medium in a dose-dependent manner. γ-Tocotrienol (800-1200 µg/egg) also inhibited new blood vessel formation on the growing chick embryo chorioallantoic membrane in a dose-dependent manner. Moreover, the inhibitory effects of γ-tocotrienol on HUVECs were correlated with inducing the apoptosis and arresting cell cycle at the G(0)/G(1) phase at a dose of 40 µmol/L γ-tocotrienol. In addition, γ-tocotrienol inhibited angiogenesis in HUVECs by down-regulation of ß-catenin, cyclin D1, CD44, phospho-VEGFR-2 and MMP-9. The antiangiogenic effects of γ-tocotrienol on HUVECs may be attributable to regulation of Wnt signaling by decreasing ß-catenin expression. Thus, our results suggest that γ-tocotrienol has a potential chemopreventive agent via antiangiogenesis.

Growth inhibition effect of ß-catenin small interfering RNA-mediated gene silencing on human colon carcinoma HT-29 cells.

The ß-catenin gene is a critical component of Wnt signaling pathway. Aberrant activation of Wnt/ß-catenin signaling and subsequent upregulation of ß-catenin is related to enhancing cell proliferation and developing colon polyps and colon cancer. In the present study, the effect of ß-catenin knockdown on the growth and survival of the human colon cancer cell line HT-29 was investigated in vitro. The effect of knockdown of ß-catenin on cell proliferation was investigated by MTT assay and colony formation. The cell cycle distribution was investigated by flow cytometry. Apoptosis was measured by nuclear staining and flow cytometry. The change of ß-catenin and related proteins were determined by western blotting and immunofluorescence. The results showed that small interfering RNA directed against ß-catenin markedly inhibited the expression and nuclear translocation of ß-catenin and decreased the expression of known target genes such as cyclin D1 and c-myc; HT-29 cell proliferation was inhibited as indicated by growth reduction, cell cycle arrest in G0/G1 phase, and induction of apoptosis; and the inhibition of cell growth may be associated with switching off cyclin D1 and c-myc expression by small interfering RNA targeted against ß-catenin in colon cancer HT-29 cells.

gamma-Tocotrienol modulates the paracrine secretion of VEGF induced by cobalt(II) chloride via ERK signaling pathway in gastric adenocarcinoma SGC-7901 cell line.

Hypoxia is a common characteristic feature of solid tumors, and carcinoma cells are known to secrete many growth factors. These growth factors, such as vascular endothelial growth factor (VEGF), play a major role in the regulation of tumor angiogenesis and metastasis. In this study, the effect of gamma-tocotrienol, a natural product commonly found in palm oil and rice bran, on the accumulation of HIF-1alpha protein and the paracrine secretion of VEGF in human gastric adenocarcinoma SGC-7901 cell line induced by cobalt(II) chloride (as a hypoxia mimic) was investigated. These results showed that cobalt(II) chloride induced the high expression of VEGF in SGC-7901 cells at dose of 150 micromol/L for 24h. Both basal level and cobalt(II) chloride-induced HIF-1alpha protein accumulation and VEGF paracrine secretion were inhibited in SGC-7901 cells treated with gamma-tocotrienol at 60 micromol/L treatment for 24 h. U0126, a MEK1/2 inhibitor, decreased the expression of HIF-1alpha protein and the paracrine secretion of VEGF under normoxic and hypoxic conditions. In this study, gamma-tocotrienol also significantly inhibited the hypoxia-stimulated expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2). The mechanism seems to involve in inhibiting hypoxia-mediated activation of p-ERK1/2, it leads to a marked decrease in hypoxia-induced HIF-1alpha protein accumulation and VEGF secretion. These data suggest that HIF-1alpha/VEGF could be a promising target for gamma-tocotrienol in an effective method of chemoprevention and chemotherapy in human gastric cancer.

Effects of beta-ionone on mammary carcinogenesis and antioxidant status in rats treated with DMBA.

Recent chemopreventive studies from our group showed that dietary beta -ionone inhibited 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis by the inhibition of cell proliferation and apoptosis initiation. In this study, we examined the chemopreventive effects of varied doses of dietary beta -ionone on the development and growth of DMBA-induced rat mammary tumors as well as plasma antioxidant status. beta -ionone treatment groups were given 9, 18, and 36 mmol/kg in the AIN76A diet starting 2 wk prior to DMBA administration and continuing for the 24 wk. Results showed that tumor incidence was dose dependently reduced by 35.4, 68.3, and 87.8%, respectively, compared to the positive control. Tumor sizes were dose dependently smaller, and tumor weight was less in each group, each rat, and each tumor compared to the positive control (P < 0.05). A significant decrease in lipid peroxidation was observed in the tumor-induced rats treated with dietary beta -ionone, whereas the plasma activities of antioxidant enzymes such as glutathione peroxidase, glutathione reductase, superoxide dismutase, and the nonenzymatic antioxidant glutathione were increased in the beta -ionone treated rats when compared to control. The levels of catalase and lactate dehydrogenase were remarkably decreased in the beta -ionone treated groups compared to the positive control group. These results suggest that dietary beta -ionone has biologically relevant antioxidant activity and plays a chemopreventive role against DMBA induced mammary gland tumors.

Inhibitory effects of gamma-tocotrienol on invasion and metastasis of human gastric adenocarcinoma SGC-7901 cells.

Natural vitamin E is a mixture of two classes of compounds, tocopherols and tocotrienols. Recent research has revealed that tocotrienols, especially gamma-tocotrienol, exhibit not only the same antioxidant ability as tocopherols, but also remarkable anticancer capacity in cancer cell lines. In this study, the invasion and metastatic capacities of gastric adenocarcinoma SGC-7901 cells and the correlation with antimetastasis mechanisms induced by gamma-tocotrienol were explored. The results showed the inhibitory effects of gamma-tocotrienol at doses of 15, 30, 45 and 60 mumol/L for 48 h on cell migration and cell matrigel invasion; activities of matrix metalloproteinase (MMPs) increased in SGC-7901 cells when compared to the control group (P<.05 or P<.01). An increasing trend in the chemotactic responses to fibronectin (FN) in SGC-7901 cells was found in the gamma-tocotrienol treatments. SGC-7901 cell attachment decreased in the gamma-tocotrienol-treated groups in comparison with the control group (P<.01). The mRNA expressions of MMP-2 and MMP-9 showed that gamma-tocotrienol significantly reduced the matrigel invasion capability through down-regulation of the mRNA expressions of MMP-2 and MMP-9 (P<.01), and up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in SGC-7901 cells by treatment with gamma-tocotrienol for 48 h (P<.05). gamma-Tocotrienol also significantly increased the mRNA expression of nm23-H1 in SGC-7901 cells (P<.01). These findings suggest a potential mechanism of gamma-tocotrienol-mediated antitumor metastasis activity and indicate the role of vitamin E as potential chemopreventative agents against gastric cancer.

Inhibition of proliferation and induction of apoptosis by gamma-tocotrienol in human colon carcinoma HT-29 cells.

OBJECTIVE: gamma-Tocotrienol is a major component of the tocotrienol-rich fraction of palm oil, but there is limited evidence that it has antitumor activity. In particular, the effects of gamma-tocotrienol on human colon carcinoma cells have not been reported. To investigate the chemopreventive effects of gamma-tocotrienol on colon cancer, we examined its capacity to inhibit proliferation and induce apoptosis in HT-29 cells and explored the mechanism underlying these effects. METHODS: We cultured HT-29 cells in the presence of gamma-tocotrienol. The effect of gamma-tocotrienol on cell proliferation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, mitotic index, and colony formation. The cell-cycle distribution was investigated by flow cytometry. We measured apoptosis by nuclear staining, transmission electron microscopy, and DNA fragmentation. Apoptosis-related proteins and the nuclear factor-kappaB p65 protein were determined by western blotting and immunofluorescence. RESULTS: gamma-Tocotrienol inhibited cell growth and arrested HT-29 cells in G(0)/G(1) phase. The 50% inhibitory concentration was 31.7 micromol/L (48 h). gamma-Tocotrienol-induced apoptosis in HT-29 cells was accompanied by downregulation of Bcl-2, upregulation of Bax, and activation of caspase-3. Furthermore, we found that gamma-tocotrienol reduced the expression level of total nuclear factor-kappaB p65 protein and inhibited its nuclear translocation. CONCLUSION: The results indicated that gamma-tocotrienol inhibits cell proliferation and induces apoptosis in HT-29 cells in a time- and dose-dependent manner, and that this process is accompanied by cell-cycle arrest at G(0)/G(1), an increased Bax/Bcl-2 ratio, and activation of caspase-3. Our data also indicated that nuclear factor-kappaB p65 protein may be involved in these effects.

Genotoxicity of water from the Songhua River, China, in 1994-1995 and 2002-2003: Potential risks for human health.

A previous study showed that the cancer mortalities are higher for residents who lived nearby the Songhua River heavily polluted by organic contamination. It is important to determine its risk of carcinogenic potential. Short-term genotoxic bio-assays using Salmonella, Sister Chromatid Exchange (SCE), and Micronuclei (MN) assays were employed to examine the genotoxic activity of ether extracts of water samples taken from the Songhua River. The results of the Salmonella bioassay indicated that there were indirect frame-shift mutagens in the water samples. A dose-response relationship for the SCE and MN assays was obtained. These results showed that organic extracts of water samples have genotoxic activity and the risk of carcinogenic potential to human health. The mutagenesis of water samples had changed compared to the results in 1994-1995. An increasing trend of risk of carcinogenic potential in the Songhua River after ten years should be noted and needs to be studied further.

Fresh apples suppress mammary carcinogenesis and proliferative activity and induce apoptosis in mammary tumors of the Sprague-Dawley rat.

Whole apple extracts possess potent antioxidant activity and antiproliferative activity against cancer cells in vitro. The objectives of this study were to determine the anticancer activity of apple extracts in a rat mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and to determine if apple extracts inhibited cell proliferation and affected apoptosis in mammary cancer tissues in vivo. Rats were given the whole apple extracts (0, 3.3, 10.0, or 20.0 g/kg of body weight) by gavage starting 2 weeks prior to DMBA administration and continuing for 24 weeks. Rats treated with DMBA (positive control) developed mammary tumors with 71.4% tumor incidence during the 24-week study. No tumors were detected in the negative control group untreated with DMBA. A dose-dependent inhibition of mammary carcinogenesis by apple extracts was observed (P < 0.01). Tumor multiplicity decreased with increasing apple extracts. Histopathological evaluations of tumors were performed. The proportions of adenocarcinoma masses decreased with increasing apple extracts. The expression of proliferating cell nuclear antigen (PCNA), cyclin D1, and Bcl-2 decreased, and Bax expression and apoptosis increased with increasing apple extracts. These results demonstrate the potent capacity of fresh apples to suppress DMBA-initiated mammary cancers in rats.

beta-Ionone suppresses mammary carcinogenesis, proliferative activity and induces apoptosis in the mammary gland of the Sprague-Dawley rat.

beta-Ionone demonstrates potent anticancer activity both in vitro and in vivo. We determined tumor incidence and the number of rats bearing tumors as well as cell proliferation and apoptosis in a rat mammary cancer model induced by 7, 12-dimethylbenz[a]anthracene (DMBA). Rats were fed an AIN-76A diet containing beta-ionone (0, 9, 18 or 36 mmol/kg), starting 2 weeks before DMBA administration and continuing for 24 weeks. A dose-dependent inhibition of mammary carcinogenesis by dietary beta-ionone was observed. Corresponding tumor incidence values were 82.1, 53.3, 25.9 and 10.0% (p < 0.01 or 0.05). Time to tumor appearance increased and tumor multiplicity decreased with increasing dietary beta-ionone. Histopathological and immunohistochemical evaluations of tumors were performed on the 64, 31, 15 and 3 tumors, respectively, identified in rats from the respective groups of 30. The proportions of adenocarcinomas, adenomas and benign masses were equally distributed in the latter group. In proportions within the other groups, the proportions of adenocarcinomas and benign masses decreased and increased with increasing dietary beta-ionone. Proliferating cell nuclear antigen (PCNA), cyclin D1 and Bcl-2 expression decreased, and Bax expression and nuclear fragmentation increased with increasing dietary beta-ionone. These results demonstrate the potent capacity of dietary beta-ionone to suppress DMBA-initiated mammary cancer in rats.

Genotoxic activity of organic contamination of the Songhua River in the north-eastern region of the People's Republic of China.

The Songhua River is one of the biggest rivers in China and is the major freshwater source for industry and agriculture, as well as the source of the drinking water for millions of residents living along it. Heavy contamination of the Songhua River is due to domestic sewage and industrial wastewater. Thus, we set out to determine the carcinogenic potential of water samples taken from drinking water source of Harbin city in the Songhua River. Short-term genotoxic bioassays using Ames, SCE, and cell transformation assays were employed to examine the genotoxic activity of the ether extracts of water samples taken from the Songhua River. The results of the Ames test indicated that there were frame shift mutagens in the water samples, which were both direct and indirect. A dose-response relationship for the SCE assay was obtained, and the SCE cumulative frequency moved obviously to the right with increasing doses of water samples. Typical transformed foci were formed in NIH3T3 cells induced by ether extracts of water samples and the transformation frequency showed a dose-response relationship. The transformed cells showed the characteristics of malignant cells. All of the results indicated that the ether extracts of water samples taken from the Songhua River showed genotoxic activity.

[Study on inhibitory effects of c9, t11-conjugated linoleic acid on migration of human gastric carcinoma cell line via cyclooxygenase-2 pathway].

OBJECTIVE: To study the inhibitory effects of c9, t11-conjugated linoleic acid (c9, t11-CLA) on migration of human gastric carcinoma cell line (SGC-7901) via cyclooxygenase-2 (COX-2) pathway. METHODS: After inhibiting COX-2 activity by 100 micromol/L COX-2 inhibitor NS-398 in SGC-7901 cell, we treated SGC-7901 cells with c9, t11-CLA at a concentration of 200,100, 50, 25 micromol/L for 24 h, respectively. Using reconstituted basement membrane invasion, adhesion, chemotaxis assays, we detected the effect of c9, t11-CLA and COX-2 on the cell migration. RESULTS: Compared to NS-398 group, 200, 100 micromol/L c9, t11-CLA significantly suppressed SGC-7901 cells invading into the reconstituted basement membrane (F = 14.309, P = 0.000; F = 19.005, P = 0.000). 200 micromol/L c9, t11-CLA significantly inhibited SGC-7901 cells adhering to laminin, fibronectin and Matrigel (F = 3.063, P = 0.021; F = 6.692, P = 0.001; F = 11.999, P = 0.000). The chemotaxis of SGC-7901 cells and inhibitory frequency were significantly decreased in the 200 micromol/L c9, t11-CLA group (F = 1.380, P = 0.276). CONCLUSION: c9, t11-CLA inhibits invasion, adhesion and chemotaxis of SGC-7901 cells, and the COX-2 plays an important role in the process. [ Key words]

[Inhibitory effect of potential metastasis in SGC-7901 cells induced by beta-ionone].

OBJECTIVE: To determine the effect of beta-ionone on the potential metastasis of human gastric adenocarcinoma cell line SGC-7901 and the underlying mechanism. METHODS: Using curve of cellular growth, Zymograms, and RT-PCR assays, we analyzed the growth rate, the activities of two types IV collagenase of Matrix met alloproteinase 9 (MMP-9) and MMP-2 and the expression of nm23-H1 gene, tissue inhibitor of met alloproteinase 1 (TIMP-1) and TIMP-2 in SGC-7901 cells which were treated with progressively increasing concentrations (25, 50, 100 and 200 micromol/L) of beta-ionone for 24 h and 48 h. RESULTS: The growth of SGC-7901 cells was inhibited by beta-ionone. Eight days after treatment with different concentrations of beta-ionone, as mentioned above, the inhibition rates were 25.93%, 28.21%, 74.36% and 90.11%, respectively compared to the negative control. The estimated IC50 value of beta-ionone for SGC-7901 cells was estimated to be 89 micromol/L; beta-ionone did not show any effect on the activities of MMP-9 and MMP-2 in SGC-7901 cells. However, the expression of nm23-H1, TIMP-1 and TIMP-2 mRNA transcripts gradually increased in response to beta-ionone in a dose-dependent manner. CONCLUSION: beta-ionone can inhibit the growth and proliferation of SGC-7901 cells. It may show some effects on the potential metastasis of SGC-7901 cells indicates by its upregulation of nm23-H1, TIMP-1 and TIMP-2 expression. However, beta-ionone may have no effect on the activities of type IV collagenase in SGC-7901 cells. The mechanism by which beta-ionone inhibits the potential metastasis of SGC-7901 cells needs to be studied further.

[Role of cyclooxygenase-2 in inhibition of human gastric adenocarcinoma cell line SGC-7901 by c9, t11-conjugated linoleic acid].

OBJECTIVE: To study the effects of c9, t11-conjugated linoleic acid (c9, t11-CLA) on the critical enzyme (COX-2) and its product - prostaglandin E2 (PGE2) of linoleic acid metabolism path in human gastric adenocarcinoma cell line (SGC-7901). METHODS: Expression of COX-2 mRNA and protein were measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, PGE2 was determined by radioimmunoassay (RIA). RESULTS: At the concentrations of 25, 50, 100, 200 pmol/L, c9, t11-CLA suppressed the expression of COX-2 mRNA, protein and PGE. CONCLUSION: COX-2 is involved anti-cancer action of c9, t11-CLA and is likely to act as an important target.

[Effects of conjugated linoleic acid on the expression of critical enzymes of linoleic acid metabolism in tumor cell].

OBJECTIVES: To study the effects of c9,t11-conjugated linoleic acid (c9,t11-CLA) on critical enzymes of linoleic acid metabolism in stomach granular cell (SGC-7901). METHODS: SGC-7901 was treated with c9,t11-CLA by 200, 100, 50 or 25 micromol/L for 24 hours. The effects of c9,t11-CLA on the cell proliferation was measured by monotetrazolium and the expression of Delta6-desaturase, Delta5-desaturase, COX-1, COX-2, 5-LOX mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: At a concentration of 200, 100, 50, or 25 micromol/L, c9,t11-CLA suppressed the proliferation of SGC-7901 by 54.3%, 20.5%, 10.5% and 2.93%. The c9,t11-CLA might decrease the expression of COX-2 mRNA, and increase the expression of Delta6-desaturase and COX-1 in SGC-7901, but might not affect Delta5-desaturase and 5-LOX. CONCLUSION: The effects of c9,t11-CLA on the COX and Delta6-desaturase might play an important role in mediating the ability of c9,t11-CLA as to inhibiting the proliferation of tumor cells, and the anti-cancer activity by c9,t11-CLA might be associated with the linoleic acid metabolism.

Effects of c9,t11-conjugated linoleic acid on adhesion of human gastric carcinoma cell line SGC-7901.

AIM: To investigate the effect of c9,t11-conjugated linoleic acid (c9,t11-CLA) on the adhesion of human gastric carcinoma cell line (SGC-7901). METHODS: SGC-7901 cells were at first treated with different concentrations (25, 50, 100, 200 micromol/L) of c9,t11-CLA and 1 mL/L ethanol (as a negative control) for 24 h. Using adhesion assay and Western blot, we investigated the ability of SGC-7901 cells to adhere to intracellular matrix and examined the expression of E-cadherin (ECD), alpha-catenin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in these cells. RESULTS: The attachment rate to laminin of SGC-7901 cells treated with different concentrations of c9,t11-CLA (0, 25, 50, 100, and 200 micromol/L) was 100.0+/-3.3, 95.7+/-4.0, 89.2+/-4.6, 87.9+/-6.1, and 65.9+/-5.8, respectively. The attachment rate to fibronectin was 100.0+/-4.7, 96.8+/-3.8, 94.5+/-4.1, 76.5+/-4.3, and 61.8+/-4.8, respectively. The attachment rate to Matrigel was 99.9+/-6.6, 91.4+/-6.8, 85.5+/-7.4, 79.3+/-5.6, and 69.6+/-5.1, respectively. Besides, c9,t11-CLA could increase the level of ECD and alpha-catenin, and decrease the level of ICAM-1 and VCAM-1 in SGC-7901 cells. CONCLUSION: c9,t11-CLA can reduce the adhesion of human gastric carcinoma cells to laminin, fibronectin and Matrigel. c9,t11-CLA can increase the level of ECD and alpha-catenin, and decrease the level of ICAM-1 and VCAM-1 in human gastric carcinoma cells.

[The effects of conjugated linoleic acid on the ability of murine macrophage in killing tumor cells].

OBJECTIVE: To study the effects of c9,t11-conjugated linoleic acid on the killing ability of macrophage to B16-MB cells in C57 mice and explore its possible mechanism. METHODS: The five levels of CLA was designed as 0, 25, 50, 75, 100 micro mol/L. After macrophage was treated with CLA for 24 h, the killing ability of macrophage on B16-MB cells was evaluated by MTT, The expression of C57 mice macrophage cytokine IL-6, TNF-alpha and iNOS mRNA was detected by RT-PCR. The expression of Erk protein was examined by Western Blot assay. RESULTS: The inhibitory effect of macrophage on tumor cell depend on the treatment of the increased c9,t11-CLA level, at the same time, the expression of IL-6, TNF-alpha and iNOS mRNA increased, the expression of Erk decreased with the elevating dose of CLA. CONCLUSIONS: c9,t11-CLA could increase the killing ability of macrophage in mice to B16-MB cells, and it was associated with induction of IL-6, TNF-alpha and iNOS mRNA expression. We speculate that antitumor ability of CLA may be associated with taking part in body immune regulation action, and the effects of CLA on the killing ability of murine macrophage to B16-MB cells was not associated with the MAPKErk pathway.

Apoptosis of human gastric adenocarcinoma cells induced by beta-ionone.

AIM: To investigate the effect of beta-ionone on the growth and apoptosis of gastric adenocarcinoma cell line SGC-7901. METHODS: Using MTT, fluorescence dye (Hoechst-33258), transmission electron microscopy and the TUNEL assay, we examined growth and apoptosis of SGC-7901 cells treated with beta-ionone at various concentrations (i.e. 25, 50, 100 and 200 micromol/L) for 24 h, 48 h. RESULTS: The growth of SGC-7901 cells was inhibited by beta-ionone. Seven days after treatment with beta-ionone at four concentrations, the inhibition rates were 12.04%, 30.59%, 78.25% and 94.15%, respectively. The IC(50) value of beta-ionone for SGC-7901 cells was estimated to be 89 micromol/L. The apoptotic morphology was demonstrated in SGC-7901 cells treated with beta-ionone by Hoechst-33258 staining and electron microscopy. Apoptosis was also shown in beta-ionone-treated SGC-7901 cells by the TUNEL assay. CONCLUSION: beta-ionone can inhibit cell proliferation and induce apoptosis of SGC-7901 cells. However, the mechanism needs to be further investigated.

Inhibition of beta-ionone on SGC-7901 cell proliferation and upregulation of metalloproteinases-1 and -2 expression.

AIM: To observe the effect of beta-ionone on the proliferation of human gastric adenocarcinoma cell line SGC-7901 and the inhibition of metalloproteinase. METHODS: Using growth inhibition, Zymograms assays and reverse transcription-polymerase-chain reaction (RT-PCR), we examined cell growth rates, activities of matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9), and expression of metalloproteinases-1 (TIMP-1) and -2 (TIMP-2) in SGC-7901 cells after the treatment with beta-ionone for 24 h and 48 h, respectively. RESULTS: beta-ionone had an inhibitory effect on the growth of SGC-7901 cells. Eight days after the treatment with beta-ionone at concentrations of 25, 50, 100 and 200 micromol/L, the inhibition rates were 25.9%, 28.2%, 74.4% and 90.1%, respectively. The IC50 value of beta-ionone for SGC-7901 cells was estimated to be 89 micromol/L. The effects of beta-ionone on MMP-2 and MMP-9 activities in SGC-7901 cells were not observed. However, the levels of TIMP-1 and TIMP-2 transcripts were elevated in cells treated with beta-ionone in a dose-dependent manner. CONCLUSION: beta-ionone can inhibit the proliferation of SGC-7901 cells, upregulate the expression of TIMP-1 and TIMP-2 expression, and may influence metastasis of cancer.