Anti-invasion and apoptosis induction of chlorella (Chlorella sorokiniana) in Hep G2 human hepatocellular carcinoma cells

The effects of 80% ethanolic extract derived from commercial granule chlorella (GPE) on cell viability, invasion capacity and apoptosis in human hepatoma cell line (Hep G2 cells) were investigated. The results demonstrated that GPE decreased cell viability, induced apoptosis and showed invasion inhibitory effects in the Hep G2 cells. GPE-triggered apoptosis was confirmed by 4′-6-diamidino-2-phenyindole (DAPI) staining and comet assay. GPE promoted an increase of reactive oxygen species (ROS) and Ca²⁺, and loss of mitochondrial membrane potential (ΔΨm) accompanied by cytochrome c release that was due to the decrease of Bcl-2 in the Hep G2 cells. GPE also induced the protein levels of apoptosis-inducing factor (AIF), increased the levels of caspase-3, -8 and -9, and stimulated the levels of fatty acid synthase (Fas) and Fas ligand (FasL) in the Hep G2 cells. Additionally GPE inhibited invasion of Hep G2 cells by down-regulation of the expression of matrix metalloproteinase (MMP)-2 and -9. Furthermore, cellular glutathione content and superoxide dismutases (SOD) activities were significantly reduced and thiobarbituric acid-reactive substances (TBARS) levels were significantly increased after GPE treatment. These results suggest that GPE can induce cytotoxicity on Hep G2 cells and inhibit the invasive capacity of malignant cells.     

Diosmin induces cell apoptosis through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells and blocks tumour growth in xenografted nude mice

This study investigated the diosmin effect on HA22T human hepatocellular carcinoma cells in vitro and in an invivo mouse xenograft model. HA22T cells were treated with different concentrations of diosmin and analysed with Western blot analysis, TUNEL, JC-1 staining and siRNA transfection assays. Additionally, the HA22T-implanted xenograft nude mice model was applied to confirm the cellular effects. Diosmin induced apoptosis, up-regulated death receptor apoptotic pathway markers as well as mitochondrial proteins. Pro-survival Bcl-2 family proteins were inhibited and the pro-apoptotic ones were increased. Protein phosphatase 2A (PP2A) siRNA or okadaic acid reversed the diosmin effects, confirming the role of PP2A in diosmin-induced HA22T apoptosis. The HA22T-implanted nude mice model revealed that diosmin inhibited tumour cell proliferation and enhanced tumour cell apoptosis. All our experimental evidence indicates that diosmin significantly promotes HA22T apoptosis and reduces tumour sizes in xenograft nude mice via PP2A in a dose-dependent manner.     

Shallot and licorice constituent isoliquiritigenin arrests cell cycle progression and induces apoptosis through the induction of ATM/p53 and initiation of the mitochondrial system in human cervical carcinoma HeLa cells

This study is the first to investigate the anticancer effect of isoliquiritigenin (ISL) in human cervical carcinoma HeLa cells. The results reveal that ISL inhibits HeLa cells by blocking cell cycle progression in the G2/M phase and inducing apoptosis. Blockade of cell cycle is associated with increased activation of ataxia telangiectasia‐mutated (ATM). Activation of ATM by ISL phosphorylated p53 at Serine15, resulting in increased stability of p53 by decreasing p53 and murine double minute‐2 (MDM2) interaction. In addition, ISL‐mediated G2/M phase arrest was also associated with decreases in the amounts of cyclin B, cyclin A, cdc2, and cdc25C, and increases in the phosphorylation of Chk2, cdc25C, and cdc2. The specific ATM inhibitor caffeine significantly decreased ISL‐mediated G2/M arrest by inhibiting the phosphorylation of p53 (Serine15) and Chk2. ISL induced apoptotic cell death is associated with changes in the expression of Bax and Bak, decreasing levels of Bcl‐2 and Bcl‐X_L, and subsequently triggering mitochondrial apoptotic pathway. In addition, pretreatment of cells with caspase‐9 inhibitor blocked ISL‐induced apoptosis, indicating that caspase‐9 activation is involved in ISL‐mediated HeLa cell apoptosis. These findings suggest that ISL may be a promising chemopreventive agent against human uterine cervical cancer.     

Caffeate derivatives induce apoptosis in COLO 205 human colorectal carcinoma cells through Fas- and mitochondria-mediated pathways

The objective of this study was to investigate the anticancer activity of caffeate derivatives in human cancer cells. Our results demonstrate that caffeate derivatives decreased the population growth of COLO 205, assessed using the MTT assay. However, caffeate derivatives, at the concentrations used in this study (0-250 μM) did not affect the viability of HepG2, Huh7, PLC5, and SK-Hep-1 cells. Flow cytometric analysis of COLO 205 cells exposed to decyl caffeate showed that the number of apoptotic cells increased in a time- and dose-dependent manner. Western blot analysis revealed that decyl caffeate stimulated an increase in protein expression levels of p53, Fas, FasL, AIF, and Apaf-1. Additionally, treatment with decyl caffeate changed the expression levels of Bcl-2 family members and subsequently induced the activation of caspase-12, caspase-9, and caspase-3, which was followed by cleavage of PARP. Our findings highlight the chemopreventive potential of decyl caffeate.     

Enhancement of cell function through heterotypic cell-cell interactions using E-cadherin-expressing NIH3T3 cells

An epithelial cell adhesion molecule, E-cadherin was expressed in NIH3T3 fibroblasts, and cell-cell interactions between keratinocytes and fibroblasts, or between hepatocytes and fibroblasts were artificially engineered. When the E-cadherin-expressing NIH3T3 cells were co-cultured with rat hepatocytes, the cell-cell contacts were formed with high frequency, and enhanced albumin secretion was observed.     

Lycium barbarum polysaccharide inhibits the proliferation of HeLa cells by inducing apoptosis

BACKGROUND: Lycium barbarum polysaccharide (LBP), isolated with boiling water from the famous Chinese medicinal herb Lycium barbarum fruits, is one of the most important functional constituents in Lycium barbarum. In this study the effects of LBP on cell proliferation, cell cycle and apoptosis in human cervical carcinoma cells (HeLa cells) were investigated. RESULTS: LBP could inhibit the proliferation of HeLa cells by changing cell cycle distribution and inducing apoptosis. In addition, the loss of mitochondrial transmembrane potential (Δψ_m) was observed by flow cytometry and the increase of intracellular Ca²⁺ concentration was detected by laser scanning confocal microscope in apoptotic cells. At the same time, the nitric oxide content, nitric oxide synthase and inducible nitric oxide synthase activities were also increased. CONCLUSION: The inhibitory effect of LBP on the proliferation of HeLa cells was caused by inducing apoptosis through the mitochondrial pathway. The results showed that LBP can be developed as a potential chemotherapeutic agent candidate against human cervical cancer. Copyright © 2012 Society of Chemical Industry     

The chloroform fraction of guava (Psidium cattleianum sabine) leaf extract inhibits human gastric cancer cell proliferation via induction of apoptosis

The antiproliferative activities of the chloroform fraction (CF) of guava (Psidium cattleianum Sabine) leaf extract were evaluated using several cancer cell lines. Maximum cytotoxicity was observed in SNU-16, a human gastric carcinoma cell line, at concentrations of 50–100 μg/ml. Flow cytometric analysis demonstrated that CF treatment resulted in a marked accumulation of SNU-16 cells in the sub-G1 phase at concentrations of 100–200 μg/ml. The induction of apoptosis in SNU-16 cells was confirmed by immunoblotting using antibodies against Bcl-2, Bax, poly (ADP-ribose) polymerase (PARP), caspase-8, and caspase-3. The major CF phytochemicals were identified as ferulic acid, genistein, 3′, 4′, 5′ trimethoxy flavone, phlorizin, and oleanolic acid by high performance liquid chromatography coupled with a photo diode array and electrospray ionisation mass spectrometry (HPLC–PDA-ESI-MS). The results suggest that phytochemicals in the CF of guava (P. cattleianum) leaf extract induce apoptosis in SNU-16 cells. These findings may lead to new strategies for treating human gastric cancer.     

Solanum nigrum L. polyphenolic extract inhibits hepatocarcinoma cell growth by inducing G2/M phase arrest and apoptosis

BACKGROUND: Hepatocellular carcinoma (HCC) is a rapidly progressive cancer with poor prognosis. However, there have been no significant new developments in treating liver cancer. To search for an effective agent against HCC progression, we prepared a polyphenolic extract of Solanum nigrum L. (SNPE), a herbal plant indigenous to Southeast Asia and commonly used in oriental medicine, to evaluate its inhibitive effect on hepatocarcinoma cell growth. The growth inhibition of HepG2 cells in vitro and in vivo was determined in the presence of SNPE. RESULTS: We found 1 µg mL^?1 SNPE‐fed mice showed decreased tumor weight and tumor volume by 90%. Notably, 2 µg mL^?1 SNPE resulted in almost complete inhibition of tumor weight as well as tumor volume. In line with this notion, SNPE reduced the viability of HepG₂ cells in a dose‐dependent manner. HepG₂ cells were arrested in the G₂/M phase of the cell cycle; meanwhile, the protein levels of cell CDC25A, CDC25B, and CDC25C were clearly reduced. Moreover, sub‐G₁ phase accumulation and caspases‐3, 8, and 9 cleavages were induced by SNPE. CONCLUSION: This study shows that SNPE is a potent agent for HCC treatment through targeting G₂/M arrest and apoptosis induction, achieving cell growth inhibition. Copyright © 2010 Society of Chemical Industry     

Growth arrest and induction of apoptosis in high-risk leukemia cells by strawberry components in vitro

Strawberries (Fragaria x ananassa) contain phytochemicals that have anti-inflammatory and anti-cancer activity. We investigated the ability of purified strawberry fractions to induce apoptotic cell death in pre-B acute lymphoblastic leukemia (ALL) lines, including lines derived from patients with high-risk B-ALL carrying the t(4;11)(q21;q23) chromosomal translocation. The isolated strawberry constituents were first screened for their anti-cancer activity using a 24 h fluorescence microplate method for detecting mitochondrial membrane depolarization. Active samples were further investigated for induction of apoptosis after addition of multiple doses to the leukemia cells over a period of 72 h. Quercetin, kaempferol, and ellagic acid induced significant apoptosis in the three cancer cell lines, as measured by loss of nuclear DNA, loss of mitochondrial membrane potential, and activation of caspase-3. Our data show that constituents of strawberries induce apoptosis in high-risk leukemia cells and may have potential in the prevention or treatment of this disease.