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1.
Delta(12)-Prostaglandin (PG) J(2) is known to elicit an anti-neoplastic effects via apoptosis induction. Previous study showed Delta(12)-PGJ(2)-induced apoptosis utilized caspase cascade through cytochrome c-dependent pathways in HeLa cells. In this study, the cellular mechanism of Delta(12)-PGJ(2)- induced apoptosis in HeLa cells, specifically, the role of two mitochondrial factors; bcl-2 and apoptosis-inducing factor (AIF) was investigated. Bcl-2 attenuated Delta(12)-PGJ(2)-induced caspase activation, loss of mitochondrial transmembrane potential (Deltapsi(m)), nuclear fragmentation, DNA laddering, and growth curve inhibition for approximately 24 h, but not for longer time. AIF was not released from mitochondria, even if the Deltapsi(m) was dissipated. One of the earliest events observed in Delta(12)-PGJ(2)-induced apoptotic events was dissipation of Deltapsi(m), the process known to be inhibited by bcl-2. Pre-treatment of z-VAD- fmk, the pan-caspase inhibitor, resulted in the attenuation of ym depolarization in Delta(12)-PGJ(2)-induced apoptosis. Up-regulation of Sox-4 protein by Delta(12)-PGJ(2) was observed in HeLa and bcl-2 overexpressing HeLa B4 cell lines. Bcl-2 overexpression did not attenuate the expression of Sox-4 and its expression coincided with other apoptotic events. These results suggest that Delta(12)-PGJ(2) induced Sox-4 expression may activate another upstream caspases excluding the caspase 9-caspase 3 cascade of mitochondrial pathway. These and previous findings together suggest that Delta(12)-PGJ(2)-induced apoptosis in HeLa cells is caspase-dependent, AIF-independent events which may be affected by Sox-4 protein expression up-regulated by Delta(12)-PGJ(2).  相似文献   

2.
Cyclopentenone prostaglandins (PGs) have antiproliferative activity on various tumor cell growth in vitro. Particularly, 9-deoxy-delta(9,12)-13,14-dihydro PGD(2) (delta(12)-PGJ(2)) was reported for its antineoplastic and apoptotic effects on various cancer cells, but its mechanism inducing apoptosis is still not clear. In this study, we have characterized apoptosis induced by delta(12)-PGJ(2) in HeLa cells. Treatment of delta(12)-PGJ(2) induced apoptosis as indicated by DNA fragmentation, chromatin condensation, and formation of apoptotic body. We also observed release of cytochrome c from mitochondria and activation of caspase cascade including caspase-3, -8, and -9. And the pan-caspase inhibitor z-Val-Ala-Asp (OMe) fluoromethyl-ketone (z-VAD-fmk) and Q-Val-Asp (OMe)-CH(2)-OPH (Q-VD (OMe)-OPH) prevented cell death induced by delta(12)-PGJ(2) showing participation of caspases in this process. However, protein expression level of Bcl-2 family was not altered by delta(12)-PGJ(2), seems to have no effect on HeLa cell apoptosis. And ZB4, an antagonistic Fas-antibody, exerted no effect on the activation of caspase 8 indicating that Fas receptor-ligand interaction was not involved in this pathway. Treatment of delta(12)-PGJ(2) also leads to suppression of nuclear factor kappaB (NF-kappaB) as indicated by nuclear translocation of p65/RelA and c-Rel and its DNA binding ability analyzed by EMSA. Taken together, our results suggest that delta(12)-PGJ(2)-induced apoptosis in HeLa cell utilized caspase cascade without Fas receptor-ligand interaction and accompanied with NF-kappaB inactivation.  相似文献   

3.
Induction of apoptosis is a function of external stimuli and cellular gene expression. Many cells respond to DNA damage by the induction of apoptosis, which depends on a functional p53 protein and is signaled by elevation of p53 levels. In this study, we found that a prior exposure to mild stress (42 degrees C) can protect HepG2 (p53+/+) cells from a subsequent UVC-induced apoptosis determined by DNA fragmentation and ratio of sub-G1 peak, but no heat-enhanced protection was found in Hep3B (p53-/-) cells. Although a similar inductive pattern of HSP70 protein and mRNA was detected in the two cell lines under thermal stress, the effect of thermal stress on UVC-induced apoptosis in HepG2 and Hep3B cells was obviously different. Overexpression of HSP70 by transient transfection of HSP70 expression vector in HepG2 cells significantly inhibited UVC-induced cell death; however, this inhibitory effect did not occur in transfected-Hep3B cells. Treatment of HepG2 cells with p53-specific antisense oligonucleotide could effectively block the antiapoptotic effect of thermal stress on UVC-induced apoptosis and increase of intracellular wild-type p53 protein by transfecting wtp53 expression plasmid into Hep3B cells yielded more resistance to UVC irradiation after prior thermal stress exposure. The results reveal an involvement of p53 in the antiapoptotic effect of thermal stress on UVC irradiation. Finally, a p53 protein increase was detected in UVC-treated HepG2 cells and could be coimmunoprecipitated with HSP70 after a thermal stress treatment. Prolonged p53 binding activity and enhanced expression of p53-controlled genes such as G1 arrest and DNA damage 45 and wild-type p53 activation factor 1/Cdk-interacting protein 1 by thermal stress are also observed in UVC-irradiated HepG2 cells. Based on these results, we propose that the antiapoptotic effect of thermal stress is mediated by increasing HSP70 and modulating intracellular p53 function.  相似文献   

4.
A water‐soluble cationic gallium corrole, 5,10,15‐tris(N‐methyl‐4‐pyridyl)corrolatogallium(III) ( 3 ), was prepared and characterized. The photocytotoxicity of 3 was investigated using Hep G2 cancer cell line. Upon treatment with corrole 3 and irradiation, fragmentation of tumor cell nuclei was observed, which led to apoptosis. Flow cytometric analysis clearly showed the efficient induction of apoptotic cell death, and corrole 3 exhibited high photocytotoxicity towards Hep G2 cancer cells (IC50 = 60 nM). Furthermore, the binding behavior of corrole 3 with c‐MYC G‐quadruplex DNA, a potent target for antitumor drugs, was investigated using spectroscopic methods and molecular docking simulation. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

5.
The canine parvovirus type 2 (CPV-2) causes an acute disease in dogs. It has been found to induce cell cycle arrest and DNA damage leading to cellular lysis. In this paper, we evaluated the apoptotic potential of the “new CPV-2a” in MDCK cells and elucidated the mechanism of the induction of apoptosis. The exposure of MDCK cells to the virus was found to trigger apoptotic response. Apoptosis was confirmed by phosphatidylserine translocation, DNA fragmentation assays, and cell cycle analysis. Activation of caspases-3, -8, -9, and -12 and decrease in mitochondrial potential in CPV-2a-infected MDCK cells suggested that the CPV-2a-induced apoptosis is caspase dependent involving extrinsic, intrinsic, and endoplasmic reticulum pathways. Increase in p53 and Bax/Bcl2 ratio was also observed in CPV-2a-infected cells.  相似文献   

6.
Jellyfish venom is a rich source of bioactive proteins and peptides with various biological activities including antioxidant, antimicrobial and antitumor effects. However, the anti-proliferative activity of the crude extract of Rhopilema nomadica jellyfish venom has not been examined yet. The present study aimed at the investigation of the in vitro effect of R. nomadica venom on liver cancer cells (HepG2), breast cancer cells (MDA-MB231), human normal fibroblast (HFB4), and human normal lung cells (WI-38) proliferation by using MTT assay. The apoptotic cell death in HepG2 cells was investigated using Annexin V-FITC/PI double staining-based flow cytometry analysis, western blot analysis, and DNA fragmentation assays. R. nomadica venom displayed significant dose-dependent cytotoxicity on HepG2 cells after 48 h of treatment with IC50 value of 50 μg/mL and higher toxicity (3:5-fold change) against MDA-MB231, HFB4, and WI-38 cells. R. nomadica venom showed a prominent increase of apoptosis as revealed by cell cycle arrest at G2/M phase, upregulation of p53, BAX, and caspase-3 proteins, and the down-regulation of anti-apoptotic Bcl-2 protein and DNA fragmentation. These findings suggest that R. nomadica venom induces apoptosis in hepatocellular carcinoma cells. To the best of the authors’ knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest of R. nomadica jellyfish venom.  相似文献   

7.
Photodynamic therapy (PDT) may trigger apoptosis or necrosis in cancer cells. Several steps in the induction and execution of apoptosis require high amounts of adenosine-5'-triphosphate (ATP). Because the mitochondrial membrane potential (delta psi) decreases early in apoptosis, we raised the question about the mechanisms of maintaining a sufficiently high ATP level. We therefore monitored delta psi and the intracellular ATP level of apoptotic human epidermoid carcinoma cells (A431) after photodynamic treatment with aluminum (III) phthalocyanine tetrasulfonate. A maximum of caspase-3-like activity and nuclear fragmentation was found at fluences of about 4 J cm(-2). Under these conditions apoptotic cells reduced delta psi rapidly, while the ATP level remained high for 4-6 h after treatment for cells supplied with glucose. To analyze the contribution of glycolysis to the energy supply during apoptosis, experiments were carried out with cells deprived of glucose. These cells showed a rapid drop of ATP content and neither caspase activation nor nuclear fragmentation could be detected. We conclude that the use of glucose as a source of ATP is obligatory for the execution of PDT-induced apoptosis.  相似文献   

8.
Proton beam is useful to target tumor tissue sparing normal cells by allowing precise dose only into tumor cells. However, the cellular and molecular mechanisms by which proton beam induces tumor cell death are still undefined. We irradiated three different tumor cells (LLC, HepG2, and Molt-4) with low energy proton beam (35 MeV) with spread out Bragg peak (SOBP) in vitro, and investigated cell death by MTT or CCK-8 assay at 24 h after irradiation. LLC and HepG2 cells were sensitive to proton beam at over 10 Gy to induce apoptosis whereas Molt-4 showed rather low sensitivity. Relative biological effectiveness (RBE) values for the death rate relative to gamma-ray were ranged from 1.1 to 2.3 in LLC and HepG2 but from 0.3 to 0.7 in Molt-4 at 11 d after irradiation by colony formation assay. The typical apoptotic nuclear DNA morphological pattern was observed by staining with 4'-6-diamidino-2-phenylindole (DAPI). Tiny fragmented DNA was observed in HepG2 but not in Molt-4 by the treatment of proton in apoptotic DNA fragment assay. By FACS analysis after stained with FITC-Annexin-V, early as well as median apoptotic fractions were clearly increased by proton treatment. Proton beam-irradiated tumor cells induced a cleavage of poly (ADP-ribose) polymerase-1 (PARP-1) and procaspases-3 and -9. Activity of caspases was highly enhanced after proton beam irradiation. Reactive oxygen species (ROS) were significantly increased and N-acetyl cysteine pretreatment restored the apoptotic cell death induced by proton beam. Furthermore, p38 and JNK but not ERK were activated by proton and dominant negative mutants of p38 and JNK revived proton-induced apoptosis, suggesting that p38 and JNK pathway may be activated through ROS to activate apoptosis. In conclusion, our data clearly showed that single treatment of low energy proton beam with SOBP increased ROS and induced cell death of solid tumor cells (LLC and HepG2) in an apoptotic cell death program by the induction of caspases activities.  相似文献   

9.
A series of novel 1,3,4-oxadiazole derivatives (OSD, OCOD, ONOD, OPD, COD, PMOD, and PCOD) were synthesized and characterized. Their structures were confirmed on the basis of IR, NMR and mass spectroscopy and molecular weights were found in the range 300–325 g/mol. Cancerous cell lines (MCF-7, HepG2) and non-cancerous cell lines (Chang liver cells) were treated with these compounds for 48 h, which caused dose dependent decrease in the cell viability. From the seven derivatives, OSD was found to be most potent with IC50 value close to 50 μM on all tested cell lines. Hence, this compound was selected for mechanistic study on HepG2 cell lines. Fluorescent cell staining and DNA fragmentation study of 50 μM OSD on HepG2 cells, showed events marked by apoptosis such as nuclear fragmentation, cytoplasm shrinkage and DNA damage. Further, the cells with same treatment were quantified for apoptosis using annexin V-PI flow cytometric technique. The percentage of apoptotic cells was significantly higher (p < 0.05) after OSD treatment compared to control cells. OSD induced a significant increase (p < 0.05) in the expression of the tumor suppressor p53 in HepG2 cells. The constitutive expression of anti-apoptotic protein Bcl-2 significantly decreased (p < 0.05) after treatment, while the expression of proapoptotic protein Bax significantly increased (p < 0.05). The change in Bax to Bcl-2 ratio suggested involvement of Bcl-2 family in induction of apoptosis. Furthermore, the levels of caspase-9 and caspase-3 were significantly (p < 0.05) up regulated in HepG2 cells after OSD treatment. The data suggest that 1,3,4-oxadiazole derivatives induce apoptosis mediated by intrinsic pathway of apoptosis. The findings strengthen the potential of the 1,3,4-oxadiazole scaffold OSD, as an agent with chemotherapeutic and cytostatic activity in human hepatocellular carcinoma in vitro.  相似文献   

10.
Aminopyropheophorbide (APP) is a second generation of photosensitizer for photodynamic therapy (PDT). We demonstrated that APP strongly absorbed red light and, after being taken up by colon cancer cells (HCT-116 cells), was localized in cytoplasmic and internal membranes but not in mitochondria. The APP-mediated photosensitization was cytotoxic for HCT-116 cells through an induction of apoptosis. Indeed, DNA fragmentation (DNA laddering and terminal deoxyuridine nick-end labeling) and chromatin condensation (4',6-diamidine-2'-phenylindole staining) could be visualized soon after photosensitization. Because nuclear factor (NF)-kappa B is involved in the response to many photosensitizers, we also demonstrated its nuclear translocation in two waves: a rapid and transient one, followed by a slow and sustained phase. The NF-kappa B turned out to be involved in an antiapoptotic response to APP-mediated photosensitization because the HCT-116 cell line expressing the dominant negative mutant of inhibitor-kappa B alpha was more sensitive to apoptosis as measured by DNA fragmentation and caspase activation. These data unambiguously show that a membrane-located photosensitizer can lead to effective apoptosis, reinforcing the idea that PDT can be an effective means to eradicate colon cancer cells.  相似文献   

11.
Cellular DNA topoisomerase I is an important target in cancer chemotherapy. A chloroform extract of the root barks of Cudrania tricuspidata showed an inhibitory effect on mammalian DNA topoisomerase I. The topoisomerase I inhibitory compound was purified and identified as 2',5,7-trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone. The compound, temporarily designated as PKH-3, was shown to inhibit the activity of topoisomerase I with IC50 about 1.0 mM. Concentration of 10 microM PKH-3 caused 50% growth inhibition of human cancer cell U937. PKH-3-induced cell death was characterized with the cleavage of poly(ADP-ribose) polymerase (PARP) and pro-caspase 3. Furthermore, PKH-3 induced the fragmentation of DNA into multiples of 180 b.p. (an apoptotic DNA ladder), indicating that the inhibitor triggered apoptosis. This induction of apoptosis by PKH-3 was also confirmed using flow cytometry analysis. Taken together, these results suggest that PKH-3 may function by inhibiting oncogenic disease, at least in part, through the inhibition of topoisomerase I activity.  相似文献   

12.
Fatty acid-CoA ligase 4 (FACL4) is a central enzyme controlling the unesterified free arachidonic acid (AA) level in cells and the free AA is known to induce apoptosis. We have recently reported that expression of FACL4 is upregulated in about 40% of human hepatocellular carcinoma (HCC) and 50% of HCC cell lines, suggesting that FACL4 may be involved in liver carcinogenesis. In this study, we investigated whether HCC cell growth is regulated by FACL4. Immunoblot analysis showed that SNU 398 cells express very low or no detectable level of FACL4. We, therefore, transfected the SNU 398 cells with FACL4 expression vector, and clones expressing FACL4 were pooled and analyzed. We found that forced expression of FACL4 in SNU 398 promotes the growth of cells. In addition, we observed that triacsin C, a FACL4 inhibitor, inhibits the growth of Hep 3B cell line which expresses high level of endogenous FACL4. We also found that the triacsin C-mediated growth inhibition in Hep 3B cells results from the induction of apoptosis with evidence of Bcl-2 reduction. Altogether, our data show that FACL4 affects HCC cell growth and suggest that modulation of FACL4 expression/activity is an approach for treatment of HCC.  相似文献   

13.
Corchorus olitorius L., is a culinary and medicinal herb, widely used as a vegetable in several countries in Asia. Many studies have shown that C. olitorius contains several antioxidants and exhibits anti-inflammatory and anti-proliferative activities in various in vitro and in vivo settings. Recently, C. olitorius has been approved for its antitumor activity; however, the underlying molecular mechanisms remain unclear. The goal of this study was to investigate the effects of ethanol extract of C. olitorius (ECO) on the growth of human hepatocellular carcinoma (HepG2) cells and gain some insights into the underlying mechanisms of its action. We found that HepG2 cells, treated with ECO for 24 h at a concentration higher than 12.5 μg/mL, displayed a strong reduction in cell viability, whereas normal FL83B hepatocytes were not affected. DNA fragmentation and nuclear condensation were evidenced by the increased subG1 population of ECO-treated HepG2 cells. ECO triggered the activation of procaspases-3 and -9 and caused the cleavage of downstream substrate, poly ADP-ribose polymerase (PARP), followed by down-regulation of the inhibitor of caspase-activated DNase (ICAD) signaling. Moreover, the increased release of cytochrome c from mitochondria with decreased membrane potential demonstrated the apoptosis induced through the caspases cascade. Our findings indicated that ECO might be effective against hepatocellular carcinoma through induction of apoptosis via mitochondria-dependent pathway.  相似文献   

14.
将人的诱导型一氧化氮合成酶(hiNOS)启动子构建在带荧光素酶基因的载体pGL3-basic上, 构建成用荧光素酶为系统的启动子, 以研究载体p8.3iNOS. 结果显示, 肾母细胞肿瘤抑制因子(WT1)能够有效地抑制hiNOS启动子的转录; 且WT1的4个选择性剪接本的抑制效果有所不同, 其中WT1(-/-)在两种肝癌细胞(HepG2和Hep3B)中对hiNOS的表达均具有最强的抑制作用, 并且抑制效果具有剂量依赖性, 用Western blot检测结果进一步证实HepG2细胞中WT1(-/-)过量表达能下调hiNOS表达. 以上结果说明WT1在肝癌细胞中对人的hiNOS具有转录调节作用.  相似文献   

15.
This study aimed to investigate the protective effect of black raspberry anthocyanins (BRAs) against acute and subacute alcoholic liver disease (ALD). Network analysis and docking study were carried out to understand the potential mechanism. Thereafter, the serum biochemical parameters and liver indexes were measured, the histopathological changes of the liver were analyzed in vivo. The results showed that all tested parameters were ameliorated after the administration of BRAs with alcohol. Meanwhile, there was increased protein expression of NF-κB and TGF-β in extracted livers, which was associated with hepatitis and hepatic fibrosis. Furthermore, BRAs and cyanidin-3-O-rutinoside exhibited cytotoxic effects on t-HSC/Cl-6, HepG2, and Hep3B and induced the apoptosis of HepG2 cells; downregulated the protein expression level of Bcl-2; upregulated the level of Bax; and promoted the release of cytochrome C, cleaved caspase-9, cleaved caspase-3, and cleaved PARP in HepG2 cells. In addition, the antioxidant activity of BRAs was tested, and the chemical components were analyzed by FT-ICR MS. The results proved that BRAs exert preventive effect on ALD through the antioxidant and apoptosis pathways.  相似文献   

16.
A number of 2,3-diarylquinoline derivatives were synthesized and evaluated for antiproliferative activities against the growth of six cancer cell lines including human hepatocellular carcinoma (Hep G2 and Hep 3B), non-small cell lung cancer (A549 and H1299), and breast cancer (MCF-7 and MDA-MB-231) cell lines. The preliminary results indicated that 6-fluoro-2,3-bis{4-[2-(piperidin-1-yl)ethoxy]phenyl}quinoline (16b) was one of the most active compounds against the growth of Hep 3B, H1299, and MDA-MB-231 with a GI(50) value of 0.71, 1.46, and 0.72 μM respectively which was more active than tamoxifen. Further investigations have shown that 16b induced cell cycle arrest at G2/M phase followed by DNA fragmentation via an increase in the protein expression of Bad, Bax and decrease in Bcl-2, and PARP which consequently cause cell death.  相似文献   

17.
A series of 3-ethyl(methyl)-2-thioxo-2,3-dihydrobenzo[g]quinazolines (1–17) were synthesized, characterized, and evaluated in vitro for their antiangiogenesis VEGFR-2-targeting, antiproliferative, and antiapoptotic activities against breast MCF-7 and liver HepG2 cells. Flow cytometry was used to determine cancer-cell cycle distributions, and apoptosis was detected using annexin-V-FITC (V) and propidium iodide (PI) dyes. Fluorescence microscopy, in combination with Hoechst staining was used to detect DNA fragmentation. Most of the tested benzo[g]quinazolines demonstrated promising activity (IC50 = 8.8 ± 0.5–10.9 ± 0.9 μM) and (IC50 = 26.0 ± 2.5–40.4 ± 4.1 μM) against MCF-7 and HepG2, respectively. Doxorubicin was used as a reference drug. Compounds 13–15 showed the highest activity against both cancer cell lines. Differential effects were detected by cell-cycle analysis, indicating similarities in the actions of 13 and 14 against both MCF7 and HepG2, involving the targeting of G1 and S phases, respectively. Compound 15 showed similar indices against both cells, indicating that its cytotoxicity toward the examined cancer cells could be unselective. Interestingly, 14 and 15 showed the highest apoptosis (30.76% and 25.30%, respectively) against MCF-7. The DNA fragmentation results agreed well with the apoptosis detected by flow cytometry. In terms of antiangiogenesis activity, as derived from VEGFR-2 inhibition, 13 and 15 were comparable to sorafenib and effected 1.5- and 1.4-fold inhibition relative to the standard sorafenib. A docking study was conducted to investigate the interaction between the synthesized benzo[g]quinazolines and the ATP-binding site within the catalytic domain of VEGFR-2.  相似文献   

18.
Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that girinimbine decreased cell viability and increased cytotoxicity in a dose-and time-dependent manner selectively. Girinimbine-treated HepG2 cells showed typical morphological features of apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay. Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time-dependent accumulation of the Sub-G(0)/G(1) peak (hypodiploid) and caused G(0)/G(1)-phase arrest. Together, these results demonstrated for the first time that girinimbine could effectively induce programmed cell death in HepG2 cells and suggests the importance of conducting further investigations in preclinical human hepatocellular carcinoma models, especially on in vivo efficacy, to promote girinimbine for use as an anticancer agent against hepatocellular carcinoma.  相似文献   

19.
Diallyl disulfide (DADS) induced apoptosis through the caspase-3 dependent pathway in leukemia cells was earlier reported from this laboratory. In this study, we investigated the involvement of Ca(2+) in DADS-induced apoptotic cell death of HCT-15, human colon cancer cell line. DADS induced the elevation of cytosolic Ca(2+) by biphasic pattern; rapid Ca(2+) peak at 3 min and following slow and sustained elevation till 3 h after the addition of DADS. Production of H(2)O(2) was also observed with its peak value at 4 h. Apoptotic pathways including the sequence of caspase-3 activation, poly(ADP-ribose) polymerase cleavage, and DNA fragmentation by DADS were completely blocked by various inhibitors such as specific caspase-3 inhibitor, free radical scavenger, and intracellular Ca(2+) chelator. N-acetylcystein and catalase treatment prevented the accumulation of H2O2 and later caspase-3 dependent apoptotic pathway. However, these radical scavengers did not block the elevation of intracellular Ca(2+). Treatment of cells with 1, 2-bis (2-aminophenoxyethane)-N, N, N-tetraacetic acid tetrakis -acetoxymethyl ester (BAPTA-AM), cellular Ca(2+) chelator, resulted in a complete blockage of the caspase-3 dependent apoptotic pathway of HCT-15 cells. It abolished the elevation of intracellular Ca(2+), and furthermore, completely inhibited the production of H(2)O(2). These results indicate that cytosolic Ca(2+) elevation is an earlier signaling event in apoptosis of HCT-15 cells. Collectively, our data demonstrate that DADS can induce apoptosis in HCT-15 cells through the sequential mechanism of Ca(2+) homeostasis disruption, accumulation of H(2)O(2), and resulting caspase-3 activation.  相似文献   

20.
The aim of this work was to further investigate the anticancer potential of Juglans mandshurica Maxim, including the separation of active constituents and their anti-proliferative effects with underlying mechanism of action. Five alkaloids (15) were isolated from the bark of J. mandshurica. Among them, 1 showed the highest cytotoxic activities against Hep3B and HepG2 cells with an IC50 values of 61.80 and 56.24 μM, respectively. Therefore, the cellular mechanism involved 1 was subsequently studied. Our results showed that 1 markedly caused apoptosis and autophagy, but without cell cycle arrest in HepG2 cells. Interestingly, only autophagic cell death was induced in 1-treated Hep3B cells. It is concluded that the isolated alkaloids exerted a certain anti-hepatoma potential, and our results may provide a basis for the further investigation of the alkaloids extracted from J. mandshurica.  相似文献   

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