共查询到20条相似文献,搜索用时 15 毫秒
1.
Hour MJ Yang JS Chen TL Chen KT Kuo SC Chung JG Lu CC Chen CY Chuang YH 《European journal of medicinal chemistry》2011,46(7):2709-2721
We designed the 6-fluoro-2-(3-fluorophenyl)-4-substituted anilinoquinazoline derivatives as less toxic anti-cancer candidates. Our result demonstrated that LJJ-10 has greater cytotoxicity than that of the other compounds in human osteogenic sarcoma U-2 OS cells. LJJ-10-induced apoptosis was associated with enhancing ROS generation, DNA damage, and an increase of the protein levels of Fas, FasL, FADD, caspase-8, cytochrome c, Apaf-1, AIF, Endo G, caspase-9 and caspase-3 in U-2 OS cells. LJJ-10-triggered growth inhibition was significantly attenuated by N-acetylcysteine, cyclosporine A, anti-FasL monoclonal antibody, and caspase-8, -9 and -3 specific inhibitors in U-2 OS cells. We suggest that LJJ-10-induced apoptotic cell death in U-2 OS cells through death receptor- and mitochondria-dependent apoptotic signaling pathways. 相似文献
2.
Wen-Tsong Hsieh Hui-Yi Lin Jou-Hsuan Chen Yueh-Hsiung Kuo Ming-Jen Fan Rick Sai-Chuan Wu 《Nutrition and cancer》2013,65(8):1339-1347
Latex of Euphorbia antiquorum (EA) has inhibitory effects on several different cancer cell lines. However, the molecular mechanism of EA inhibitory effects on human cervical cancer HeLa cell growth has not been explored. EA induced apoptosis, which was characterized by morphological change, DNA fragmentation, increased sub-G1 population, and alterations in levels of apoptosis-associated proteins. Treatment with EA increased cell death and expression levels of caspase-8, -9, and -3. EA suppressed expression of Bcl-2, increased Bax, and reduced cleavage of Bid and the translocation of tBid to the mitochondria and the release of cytochrome c from mitochondria. EA caused a loss of mitochondrial membrane potential (ΔΨm) and an increase in cellular reactive oxygen species (ROS). EA-induced ROS formation was suppressed by cyclosporine A (an inhibitor of the ΔΨm) or allopurinol (an effective scavenger of ROS). EA also increased expression of Fas, FasL, and c-Jun N-terminal kinase (JNK), p38, and mitogen-activated protein kinase (MAPK) and decreased expression of extracellular signal-regulated kinase (ERK) 1/2-p. Co-treatment with the JNK inhibitor SP600125 inhibited EA-induced apoptosis and the activation of caspase-8, -9, and -3. Results of this study provide support for the hypothesis that EA causes cell death via apoptotic pathways in human cervical adenocarcinoma HeLa cells. 相似文献
3.
4.
Induction of inflammation by West Nile virus capsid through the caspase-9 apoptotic pathway 总被引:5,自引:0,他引:5
Yang JS Ramanathan MP Muthumani K Choo AY Jin SH Yu QC Hwang DS Choo DK Lee MD Dang K Tang W Kim JJ Weiner DB 《Emerging infectious diseases》2002,8(12):1379-1384
West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. We report that the WNV-capsid by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade. 相似文献
5.
Interaction of polyunsaturated fatty acids
and sodium butyrate during apoptosis
in HT-29 human colon adenocarcinoma cells 总被引:1,自引:0,他引:1
Summary
Background
Dysregulation
of the balance between cell
growth and death in the colonic
epithelium is associated with cancer
promotion. Understanding how
cell death in this self-renewing tissue
is regulated and how it is influenced
by interaction of specific
dietary components, especially fat
and fibre, could lead to improved
treatment and prevention strategies
for cancer.
Aim of the study
The effects of two types of polyunsaturated
fatty acids (PUFAs) – arachidonic (AA, 20:4, n-6) or docosahexaenoic
(DHA, 22:6, n-3) – on the response of human colon
adenocarcinoma HT-29 cells to
sodium butyrate (NaBt) were investigated.
Methods
The parameters
reflecting cell proliferation
and cell death were studied together
with oxidative response, mitochondrial
membrane potential
(MMP) and changes of selected
regulatory molecules associated
with cell cycle (p27Kip1 and
p21Cip1/WAF1) and apoptosis (caspase-3, caspase-9, poly (ADP-ribose)
polymerase – PARP, Bcl-2,
Bax, Bak,Mcl-1).
Results
We
demonstrated that pre-treatment
with either AA or DHA attenuated
cell cycle arrest caused by NaBt
which is associated with modulation
of p27Kip1, but not p21Cip1/WAF1
protein expression. On the other
hand, PUFAs sensitised HT-29 cells
to NaBt-induced apoptosis. An increased
amount of floating cells
and cells in the subG0/G1 population
was associated with increased
reactive oxygen species production,
lipid peroxidation, decrease
of MMP, activation of caspase-3
and -9, PARP cleavage, and decrease
in the expression of antiapoptotic
Mcl-1 protein. The observed
effects were modulated by
the addition of a protein synthesis
inhibitor, cycloheximide, and partially
reversed by the antioxidant
Trolox.
Conclusions
PUFAs may
have beneficial effects in the colon
enhancing apoptosis induced by
NaBt. Alteration of cell membrane
lipid composition and potentiation
of oxidative processes accompanied
by changes in mitochondria
followed by stimulation of apoptotic
cascade components play a
role in these effects. 相似文献
6.
Granado-Serrano AB Martín MA Bravo L Goya L Ramos S 《The Journal of nutrition》2006,136(11):2715-2721
Dietary polyphenols have been associated with the reduced risk of chronic diseases such as cancer, but the precise underlying mechanism of protection remains unclear. The aim of this study was to investigate the effect of quercetin on the activation of the apoptotic pathway in a human hepatoma cell line (HepG2). Treatment of cells for 18 h with quercetin induced cell death in a dose-dependent manner; however, a shorter treatment (4 h) had no effect on cell viability. Incubation of HepG2 cells with quercetin for 18 h induced apoptosis by the activation of caspase-3 and -9, but not caspase-8. Moreover, this flavonoid decreased the Bcl-xL:Bcl-xS ratio and increased translocation of Bax to the mitochondrial membrane. A sustained inhibition of the major survival signals, Akt and extracellular regulated kinase (ERK), also occurred in quercetin-treated cells. These data suggest that quercetin may induce apoptosis by direct activation of caspase cascade (mitochondrial pathway) and by inhibiting survival signaling in HepG2. 相似文献
7.
Sok Park Mi-Young Kim Dong Ha Lee Soo Hwan Lee Eun Joo Baik Chang-Hyun Moon Se Won Park Eun Young Ko Sei-Ryang Oh Yi-Sook Jung 《European journal of nutrition》2009,48(4):235-242
Background Although there is growing awareness of the beneficial potential of onion intake to lower the risk of cardiovascular disease,
there is little information about the effect of onion on ischemic heart injury, one of the most common cardiovascular diseases.
Aim of the study This study investigates the effect of the methanol-soluble extract of onion on ischemic injury in heart-derived H9c2 cells
in vitro and in rat hearts in vivo. The underlying mechanism is also investigated.
Methods To evaluate the effect of onion on ischemia-induced cell death, LDH release and TUNEL-positivity were assessed in H9c2 cells,
and the infarct size was measured in a myocardial infarct model. To investigate the mechanism of the cardioprotection by onion,
the reactive oxygen species (ROS) level and the mitochondrial membrane potential (ΔΨm) were measured using an imaging technique; the caspase-3 activity was assayed, and Western blotting was performed to examine
cytochrome c release in H9c2 cells.
Results The methanolic extract of onion had a preventive effect on ischemia/hypoxia-induced apoptotic death in H9c2 cells in vitro
and in rat heart in vivo. The onion extract (0.05 g/ml) inhibited the elevation of the ROS, mitochondrial membrane depolarization,
cytochrome c release and caspase-3 activation during hypoxia in H9c2 cells. In the in vivo rat myocardial infarction model, onion extract
(10 g/kg) significantly reduced the infarct size, the apoptotic cell death of the heart and the plasma MDA level.
Conclusion In conclusion, the results of this study suggest that the methanolic extract of onion attenuates ischemia/hypoxia-induced
apoptosis in heart-derived H9c2 cells in vitro and in rat hearts in vivo, through, at least in part, an antioxidant effect.
S. Park and M.-Y. Kim contributed equally to this work. 相似文献
8.
The role of the mitochondria in apoptosis induced by 7beta-hydroxycholesterol and cholesterol-5beta,6beta-epoxide 总被引:3,自引:0,他引:3
Oxysterols are oxygenated derivatives of cholesterol that may be formed endogenously or absorbed from the diet. Significant amounts of oxysterols have frequently been identified in foods of animal origin, in particular highly processed foods. To date, oxysterols have been shown to possess diverse biological activities; however, recent attention has focused on their potential role in the development of atherosclerosis. Oxysterols have been reported to induce apoptosis in cells of the arterial wall, a primary process in the development of atheroma. The aim of the present study was to identify the role of the mitochondria in the apoptotic pathways induced by the oxysterols 7beta-hydroxycholesterol (7beta-OH) and cholesterol-5beta,6beta-epoxide (beta-epoxide) in U937 cells. To this end, we investigated the effects of these oxysterols on mitochondrial membrane potential, caspase-8 activity, the mitochondrial permeability transition pore and cytochrome c release. 7beta-OH-induced apoptosis was associated with a loss in mitochondrial membrane potential after 2 h, accompanied by cytochrome c release from the mitochondria into the cytosol after 16 h. Pre-treatment with a range of inhibitors of the mitochondrial permeability transition pore protected against 7beta-OH-induced cell death. In contrast, beta-epoxide induced a slight increase in caspase-8 activity but had no effect on mitochondrial membrane potential or cytochrome c release. The present results confirm that 7beta-OH-induced apoptosis occurs via the mitochondrial pathway and highlights differences in the apoptotic pathways induced by 7beta-OH and beta-epoxide in U937 cells. 相似文献
9.
Role of caspase-8 activation in mediating vitamin E-induced apoptosis in murine mammary cancer cells 总被引:8,自引:0,他引:8
The vitamin E family of compounds is divided into two subgroups, tocopherols and tocotrienols. However, tocotrienols display more potent apoptotic activity in mammary cancer cells. Although the mechanism(s) mediating tocotrienol-induced apoptosis is presently unknown, apoptosis is carried out by activation of initiator caspases (caspase-8 or -9) that subsequently activate effector caspases (caspase-3, -6, or -7). Studies were conducted to determine whether tocotrienol-induced apoptosis is mediated by activation of the caspase-8 and/or caspase-9 pathway. Highly malignant +SA mouse mammary epithelial cells were grown in culture and maintained on serum-free media. Treatment with tocotrienol-rich-fraction of palm oil (TRF) and g-tocotrienol, but not a-tocopherol, induced a dose-dependent decrease in +SA cell viability. TRF- and g-tocotrienol-induced cell death resulted from apoptosis, as determined by DNA fragmentation and positive TUNEL assay staining. Additional studies showed that treatment with 50 mM TRF or 20 mM g-tocotrienol increased intracellular activity and levels of processed caspase-8 and -3 but not caspase-9. Furthermore, treatment with specific caspase-8 or -3 inhibitors, but not caspase-9 inhibitor, completely blocked the tocotrienol-induced apoptosis in +SA cells. These findings demonstrate that tocotrienol-induced apoptosis in +SA mammary cancer cells is mediated through activation of the caspase-8 signaling pathway and is independent of caspase-9 activation. 相似文献
10.
Wang L Wang H Li J Chen D Liu Z 《Archives of environmental contamination and toxicology》2011,61(3):500-511
The combined effects of lead (Pb) and cadmium (Cd) on primary cultures of rat proximal tubular (rPT) cells were studied. These
cells were either treated with Pb acetate (0.5 and 1 μM) alone, Cd acetate (2.5 and 5 μM) alone, or a combination of Pb and
Cd acetate, and then joint cytotoxicity was evaluated. The results showed that the combination of these two metals decreased
cell viability and increased the number of apoptotic and necrotic cells and lactate dehydrogenase release synergistically.
Simultaneously, increased intracellular reactive oxygen species, malondialdehyde, and calcium levels and decreased mitochondrial
membrane potential, intracellular acidification, and inhibition of Na+, K+-, and Ca2+-ATPase activities were shown during the exposure. In addition, apoptotic morphological changes induced by these treatments
in rPT cells were demonstrated by Hoechst 33258 staining. The apoptosis was markedly prevented by N-acetyl-l-cysteine, whereas necrosis was not affected. In summary, there was a synergistic cytototic effect of Pb combined with Cd
on rPT cells. Cell death induced by Pb–Cd mixture was mediated by an apoptotic and a necrotic mechanism. Apoptotic death was
the chief mechanism. Changes of intracellular events were intimately correlated with both oxidative stress and mitochondrial
dysfunction, which promoted the development of apoptosis. 相似文献
11.
Hsieh WT Lin HY Chen JH Kuo YH Fan MJ Wu RS Wu KC Wood WG Chung JG 《Nutrition and cancer》2011,63(8):1339-1347
Latex of Euphorbia antiquorum (EA) has inhibitory effects on several different cancer cell lines. However, the molecular mechanism of EA inhibitory effects on human cervical cancer HeLa cell growth has not been explored. EA induced apoptosis, which was characterized by morphological change, DNA fragmentation, increased sub-G1 population, and alterations in levels of apoptosis-associated proteins. Treatment with EA increased cell death and expression levels of caspase-8, -9, and -3. EA suppressed expression of Bcl-2, increased Bax, and reduced cleavage of Bid and the translocation of tBid to the mitochondria and the release of cytochrome c from mitochondria. EA caused a loss of mitochondrial membrane potential (ΔΨm) and an increase in cellular reactive oxygen species (ROS). EA-induced ROS formation was suppressed by cyclosporine A (an inhibitor of the ΔΨm) or allopurinol (an effective scavenger of ROS). EA also increased expression of Fas, FasL, and c-Jun N-terminal kinase (JNK), p38, and mitogen-activated protein kinase (MAPK) and decreased expression of extracellular signal-regulated kinase (ERK) 1/2-p. Co-treatment with the JNK inhibitor SP600125 inhibited EA-induced apoptosis and the activation of caspase-8, -9, and -3. Results of this study provide support for the hypothesis that EA causes cell death via apoptotic pathways in human cervical adenocarcinoma HeLa cells. 相似文献
12.
Pretreatment with rituximab enhances radiosensitivity of non-Hodgkin's lymphoma cells 总被引:3,自引:0,他引:3
Skvortsova I Popper BA Skvortsov S Saurer M Auer T Moser R Kamleitner H Zwierzina H Lukas P 《Journal of radiation research》2005,46(2):241-248
The present study examines the effects of ionizing radiation in combination with rituximab (RTX), a chimeric human anti-CD20 monoclonal antibody, on proliferation, cell cycle distribution and apoptosis in B-lymphoma RL and Raji cells. Exposure to ionizing radiation (9 Gy) induced cell growth delay and apoptosis in RL cells, whereas Raji cells showed moderate radio-resistance. The simultaneous exposure of lymphoma cells to ionizing radiation and RTX (10 microg/mL) markedly enhanced apoptosis and cell growth delay in RL and Raji cells. Cooperative antiproliferative and apoptotic effects of RTX and radiation were achieved through the inhibition of c-myc and bcl-XL expression. Furthermore, RTX-modulated expression of cell cycle regulating proteins, such as p53, p21/WAF1, p27/KIP1, contributed to the development of radiation-induced cell killing and growth arrest. Each NHL cell line that underwent apoptosis induced by combination treatment revealed enhanced caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage as compared to only irradiated cells. These findings show that rituximab synergistically enhances radiation-induced apoptosis and cell growth delay through the expression of proteins involved in the programmed cell death and cell cycle regulation pathways. 相似文献
13.
Role of Caspase-8 Activation in Mediating Vitamin E-Induced Apoptosis in Murine Mammary Cancer Cells
《Nutrition and cancer》2013,65(2):236-246
The vitamin E family of compounds is divided into two subgroups, tocopherols and tocotrienols. However, tocotrienols display more potent apoptotic activity in mammary cancer cells. Although the mechanism(s) mediating tocotrienol-induced apoptosis is presently unknown, apoptosis is carried out by activation of initiator caspases (caspase-8 or -9) that subsequently activate effector caspases (caspase-3, -6, or -7). Studies were conducted to determine whether tocotrienol-induced apoptosis is mediated by activation of the caspase-8 and/or caspase-9 pathway. Highly malignant +SA mouse mammary epithelial cells were grown in culture and maintained on serum-free media. Treatment with tocotrienol-rich-fraction of palm oil (TRF) and γ-tocotrienol, but not α-tocopherol, induced a dose-dependent decrease in +SA cell viability. TRF- and γ-tocotrienol-induced cell death resulted from apoptosis, as determined by DNA fragmentation and positive TUNEL assay staining. Additional studies showed that treatment with 50 μM TRF or 20 μM γ-tocotrienol increased intracellular activity and levels of processed caspase-8 and -3 but not caspase-9. Furthermore, treatment with specific caspase-8 or -3 inhibitors, but not caspase-9 inhibitor, completely blocked the tocotrienol-induced apoptosis in +SA cells. These findings demonstrate that tocotrienol-induced apoptosis in +SA mammary cancer cells is mediated through activation of the caspase-8 signaling pathway and is independent of caspase-9 activation. 相似文献
14.
Ergül Mutlu Altunda? Ay?e Mine Y?lmaz Semra Ko?türk Yavuz Taga & A. Suha Yal??n 《Nutrition and cancer》2018,70(1):97-108
Chronic myeloid leukemia is a major hematopoietic malignancy characterized by expansion of myeloid cells. In this study, we have investigated whether quercetin, curcumin and their combination induce apoptosis and inhibit growth of K562 cells. We have observed that quercetin and curcumin combination induced apoptosis accompanied by increased ROS and decreased GSH levels as well as loss of mitochondrial membrane potential. Our mRNA and protein expression results suggested that cytochrome c was released from mitochondria causing PARP and caspase-9 cleavages, the hallmarks of mitochondrial apoptotic pathway. We believe that triggering of apoptosis is mostly via mitochondrial pathway and ROS generation may induce impairment of mitochondrial membrane potential. The use of quercetin and curcumin combination potentiates individual apoptotic effects of the polyphenols and reduces their effective dose thereby preventing potential toxic effects on normal cells. Additional preclinical studies and clinical trials are certainly required to further validate their usefulness as potent anticancer agents. 相似文献
15.
Marta Switalska Grzegorz Grynkiewicz Leon Strzadala Joanna Wietrzyk 《Nutrition and cancer》2013,65(6):874-884
Genistein is a natural compound belonging to isoflavone family of secondary plant metabolites, characterized by pleiotropic biological activity. Here we present the results of a study on new analogs and polysaccharide complexes of genistein as potent antiproliferative and cell death-inducing agents. Most potent were 2 analogs (i.e., IFG-027 and IFG-043) and 2 complexes (i.e., SPG-G and XG-G), which had higher or similar antiproliferative activity in comparison to genistein. However, these 2 analogs decreased the number of cells in G2/M phase in contrast to genistein and SPG-G complex. Genistein analogs, IFG-027 and IFG-043, and also SPG-G complex decreased mitochondrial membrane potential and induced the externalization of phosphatidylserine to the extracellular membrane site, which indicates the induction of apoptosis. Interestingly, genistein and its analogs induced caspase 3-activation supporting apoptotic mechanism of cell death but SPG-G supported caspase 3-independent apoptosis. XG-G complex probably did not induce cell death through the apoptotic pathway, as we did not find the externalization of phosphatidylserine and activation of caspase-3. After the treatment of HL-60 cells with genistein, SPG-G and XG-G formation of acidic vesicular organelle (AVO) was detected. In contrast, in the cells that were treated with genistein analogs IFG-027 and IFG-043, AVO formation was not observed. 相似文献
16.
The soy isoflavone genistein has been identified as having antiproliferative and apoptotic effects on various malignant cell types derived from solid tumors. Because little information regarding the effect of genistein on hematopoietic malignancies is available, we undertook this study of T-cell lymphomas. We tested the effect of genistein on murine T-cell lines derived from thymic lymphomas induced by an oncogenic murine leukemia virus. When T lymphoma cells were treated with genistein concentrations of 15 microM and greater, it was observed that the percentage of viable cells was significantly reduced in a dose- and time-dependent manner. The observed cell killing was found to be the result of apoptosis as detected by flow cytometric analysis of cells stained with annexin V and propidium iodide and assays for caspase-3 activation and DNA fragmentation. Cell staining with the mitochondrial specific dye JC-1 and detection of caspase-9 activation revealed that genistein produced mitochondrial depolarization as an early step in the induction of apoptosis. Bongkrekic acid inhibition of mitochondrial depolarization identified the mitochondria permeability transition pore (PTP) as a potential target of genistein activity. These results indicate that the induction of apoptosis by pharmacological concentrations of genistein in T lymphoma cells occurs via mitochondrial damage with the involvement of the PTP. 相似文献
17.
Won-Hyung Choi Jong-Phil Chu Mei-Hua Jiang Seung-Hwa Baek Hyun-do Park 《Nutrition and cancer》2013,65(1):121-129
Corni Fructus has traditionally been used as herbal medicine for the treatment of tuberculosis, asthma, hepatitis, and chronic nephritis in Korea, Japan, and China. This research was carried out to evaluate the proliferative-inhibitory effect of CF extracts against cancer cells and to identify the new pro-substance from medicinal plants. Among these herbal extracts extracted from KCF (Korean Corni Fructus), JCF (Japanese Corni Fructus) and CCF (Chinese Corni Fructus), KCF extracts strongly induced anti-proliferation of cancer cells in a dose-dependent manner compared with other extracts. Moreover, after treatment with CM/F3 (fraction 3 obtained from KCF extracts) for 24 h, A549 cells were evaluated by several indicators such as cell viability, LDH release, DNA fragmentation, nuclear condensation, and apoptotic proteins in vitro. CM/F3 showed the tumor-selective growth inhibitory activity in a dose- and time-dependent manner in A549 cells. Consistently, CM/F3 effectively induced the activation of bax, cytochrome-c, caspase-3, -8, -9, p53, and p21 causing apoptosis, and caused the suppression of Cdk2, pRb, and E2F1 related to cell arrest in A549 cells. These results demonstrate that CM/F3 caused not only anti-proliferation but also cell death involving cell arrest through interaction between apoptotic proteins and the upregulation of p53 in A549 cells. 相似文献
18.
Neuronal cell death induced by chronic stress in the central nervous system is a cause of neurological dysfunction. We investigated the neuroprotective potential of a water extract of S. takesimense (WEST) against corticosterone-induced apoptosis in PC12 cells and the possible underlying mechanisms. Cells were pretreated with 50 µg/mL of WEST to evaluate its neuroprotective effect based on endoplasmic reticulum (ER) stress inhibition and mitochondrial function improvement. Pretreatment with WEST prevented corticosterone-induced injury in PC12 cells, resulting in increased cell survival, decreased lactate dehydrogenase (LDH) release, and potent apoptosis inhibition by a reduction in apoptotic nuclei demonstrated by Hoechst 33342 and propidium iodide (PI) double staining, and TUNEL staining. WEST strongly attenuated calcium (Ca2+) elevation, inducing the closure of mitochondrial permeability transition pores (mPTPs), which were opened by corticosterone. It also stabilized mitochondrial membrane potential (MMP) loss and inhibited the corticosterone-induced decrease in adenosine triphosphate (ATP) levels. Furthermore, the increased reactive oxygen species (ROS) production induced by corticosterone was prevented in PC12 cells treated with WEST. WEST also downregulated the expression of glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), the pro-apoptotic protein Bcl-2-associated X (Bax), cytochrome c, cysteine-aspartic protease (caspase)-9, and caspase-3, and upregulated the expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). Thus, WEST exerts a neuroprotective effect by inhibiting the apoptosis pathway in ER stress and the mitochondrial dysfunction induced by corticosterone. These results demonstrate that WEST reduces neuronal damage from the neurotoxicity caused by chronic stress. 相似文献
19.
Xiaofeng Lu Haining Yu Qi Ma Shengrong Shen Undurti N Das 《Lipids in health and disease》2010,9(1):106
Some polyunsaturated fatty acids (PUFAs), if not all, have been shown to have tumoricidal action, but their exact mechanism(s)
of action is not clear. In the present study, we observed that n-6 PUFA linoleic acid (LA) inhibited tumor cell growth at
high concentrations (above 300 μM); while low concentrations (100-200 μM) promoted proliferation. Analysis of cell mitochondrial
membrane potential, reactive oxygen species (ROS) formation, malondialdehyde (MDA) accumulation and superoxide dismutase (SOD)
activity suggested that anti-cancer action of LA is due to enhanced ROS generation and decreased cell anti-oxidant capacity
that resulted in mitochondrial damage. Of the three cell lines tested, semi-differentiated colorectal cancer cells RKO were
most sensitive to the cytotoxic action of LA, followed by undifferentiated colorectal cancer cell line (LOVO) while the normal
human umbilical vein endothelial cells (HUVEC) were the most resistant (the degree of sensitivity to LA is as follows: RKO
> LOVO > HUVEC). LA induced cell death was primed by mitochondrial apoptotic pathway. Pre-incubation of cancer cells with
100 μM LA for 24 hr enhanced sensitivity of differentiated and semi-differentiated cells to the subsequent exposure to LA.
The relative resistance of LOVO cells to the cytotoxic action of LA is due to a reduction in the activation of caspase-3.
Thus, LA induced cancer cell apoptosis by enhancing cellular oxidant status and inducing mitochondrial dysfunction. 相似文献
20.
In the human colon cancer cells HCT116, deoxycholic acid (DCA) induces apoptosis via the mitochondrial pathway by triggering the release of mitochondrial factors such as cytochrome c. To elucidate if Bax, a proapoptotic member of the Bcl-2 family known to trigger cytochrome c release in response to various types of apoptotic stimuli, is involved in DCA-induced apoptosis in HCT116 cells, we analyzed DCA-induced apoptosis in Bax-knockout (Bax–/–) HCT116 cells. Cytochrome c release and caspase-9 activation were detectable after 5 min in both Bax–/– and Bax+/– HCT116 cells. Caspase-3 and caspase-8 activation was observed after 15 and 30 min, respectively. Bax–/– cells were protected from apoptosis by treating them with ursodeoxycholic acid for 12 h prior to DCA treatment. These results are consistent with our previous observations that were obtained by using wild-type HCT116 cells and suggest that Bax is not indispensable for DCA-induced apoptosis in HCT116 cells. 相似文献