Emodin induces apoptosis through caspase 3-dependent pathway in HK-2 cells

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a major constituent of rhubarb. Although it has been claimed to have a wild spectrum of therapeutic value, its side effects, especially in human kidney cells have not been well characterized. In the present study, we treated human proximal tubular epithelial cell line HK-2 cells with emodin in vitro and evaluated its toxic effects with cell viability, cell cycle phases and induction of apoptosis/necrosis and activity of caspase 3. The proliferation of HK-2 cells was inhibited by emodin in a dose- and time-dependent manner. Cell cycle analysis revealed that HK-2 cells were locked in G1 phase by emodin as for 12h. Apoptosis was supported by the Annexin V/propidium iodide (PI) assay and the occurrence of a sub-G1 peak. Emodin caused an increase in caspase 3-like activities and a caspase 3 inhibitor, Ac-DEVD-CHO, attenuated the apoptosis. These results suggested that HK-2 cells are sensitive to emodin-induced cytotoxic effects, which are mediated through the induction of apoptosis in caspase 3-dependent pathway.     

Dichloroacetonitrile induces cytotoxicity through oxidative stress-mediated and p53-dependent apoptosis pathway in LO2 cells

Dichloroacetonitrile (DCAN), one of the disinfection byproducts of water chlorination, induces cell proliferation and apoptosis; however, the detailed mechanism remains unclear. Oxidative stress participates in various biological processes, including DNA damage and cytotoxicity. To explore whether oxidative stress mediated DCAN-induced cell proliferation and apoptosis, we assessed the effect of redox imbalance and apoptosis in LO2 cells. We observed increase of reactive oxygen species and malondialdehyde and increased apoptosis by 13.6% in 500?μM DCAN compared with the control group. We also observed a decrease of antioxidant ability damage including glutathione, superoxide dismutase, and total antioxidant capacity depletion. Furthermore, DCAN might activate oxidative stress-mediated apoptosis pathway via up-regulation of p53 expression and caspase-3 activity. Therefore, we conclude that DCAN may activate apoptotic signals via p53 up-regulation and oxidative stress-mediated apoptosis in LO2 cells.     

Diepoxybutane induces caspase and p53-mediated apoptosis in human lymphoblasts

Diepoxybutane (DEB) is the most potent metabolite of the environmental chemical 1,3-butadiene (BD), which is prevalent in petrochemical industrial areas. BD is a known mutagen and human carcinogen, and possesses multiorgan systems toxicity that includes bone marrow depletion, spleen, and thymus atrophy. Toxic effects of BD are mediated through its epoxy metabolites. In working towards elucidating the cellular and molecular mechanisms of BD toxicity, we investigated the ability of DEB to induce apoptosis in human lymphoblasts. DEB induced a concentration and exposure time-dependent apoptosis, which accounted for the DEB-induced loss of cell viability observed in TK6 lymphoblasts. The DEB-induced apoptosis was inhibited by inhibitors of caspases 3 and 9. The role of p53 in mediating the DEB-induced apoptosis was also investigated. DEB induced elevated p53 levels in direct correlation to the extent of DEB-induced apoptosis, as the concentration of DEB increased up to 5 microM. The extent of DEB-induced apoptosis was dramatically higher in TK6 lymphoblasts as compared to the genetically paired p53-deficient NH32 lymphoblasts under the same experimental conditions. Our results confirm and extend observations on the occurrence of apoptosis in DEB exposed cells, and demonstrate for the first time the elevation of p53 levels in human lymphoblasts in response to DEB exposure. In addition, our results demonstrate for the first time that DEB-induced apoptosis is mediated by caspases 3 and 9, as well as the p53 protein. It is possible that DEB-induced apoptosis may explain BD-induced bone marrow depletion, spleen and thymus atrophy in BD-exposed animals.     

Indole-3-carbinol induces apoptosis through p53 and activation of caspase-8 pathway in lung cancer A549 cells

Indole-3-carbinol (I3C) has anti-tumor effects in various cancer cell lines. However, the anti-tumor effect of I3C on human lung cancers has been rarely reported. We investigated the anti-tumor effects and its mechanism of I3C on human lung carcinoma A549 cell line. Treatment of the A549 cells with I3C significantly reduced cell proliferation, increased formations of fragmented DNA and apoptotic body, and induced cell cycle arrest at G0/G1 phase. I3C increased not only the protein levels of cyclin D1, phosphorylated p53, and p21 but also the expression of Fas mRNA. Cleavage of caspase-9, -8, -3 and PARP also was increased by I3C. Treatment with wortmannin significantly suppressed both I3C-induced Ser15 phosphorylation and accumulation of p53 protein. The inhibition of caspase-8 by z-IETD-FMK significantly decreased cleavage of procaspase-8,-3 and PARP in I3C-treated A549 cells. Taken together, these results demonstrate that I3C induces cell cycle arrest at G0/G1 through the activation of p-p53 at Ser 15 and induces caspase-8 mediated apoptosis via the Fas death receptor. This molecular mechanism for apoptotic effect of I3C on A549 lung carcinoma cells may be a first report and suggest that I3C may be a preventive and therapeutic agent against lung cancer.     

Pseudolaric acid B induces apoptosis through p53 and bax/ Bcl-2 pathways in human melanoma a375-s2 cells

Pseudolaric acid B is a major compound found in the bark of Pseudolarix kaempferi Gordon. In our study, pseudolaric acid B inhibited growth of human melanoma cells, A375-S2 in a time- and dose-dependent manner. A375-S2 cells treated with pseudolaric acid B showed typical characteristics of apoptosis including morphologic changes, DNA fragmentation, sub-diploid peak in flow cytometry, cleavage of poly-ADP ribose polymerase (PARP) and degradation of inhibitor of caspase-activated DNase (ICAD). P53 protein expression was upregulated while cells were arrested at the G2/M phase of the cell cycle. There was a decrease in the expression of anti-apoptotic Bcl-2 and Bcl-xL proteins, whereas pro-apoptotic Bax was increased. The two classical caspase substrates, PARP and ICAD, were both decreased in a time-dependent manner, indicating the activation of downstream caspases.     

Hesperetin induces an apoptosis-triggered extrinsic pathway and a p53- independent pathway in human lung cancer H522 cells

We studied the chemoprevention property of hesperetin on H522 cells using MTT, an apoptosis assay, an analysis of cell cycle progression, and the mitochondrial membrane potential, and apoptotic marker gene expression was determined using quantitative PCR. Hesperetin enhanced apoptotic cell death and mitochondrial membrane potential loss in H522 cells. Hesperetin up-regulated the levels of Fas, FADD, and caspase-8 expression and downregulted the levels of caspase-3 and caspase-9, p53, and Bax expression in H522 cells. This study shows that hesperetin induces apoptosis in H522 cells via a pathway independentof p53 and Bax but triggers the death-receptor Fas-initiated FADD/ caspase-8-dependent apoptotic pathway.     

Berberine induces apoptosis through a mitochondrial/caspase pathway in human promonocytic U937 cells.

Berberine, an isoquinoline plant alkaloid, is known to generate a wide variety of biochemical and pharmacological effects. To elucidate the molecular mechanism of berberine-induced antiproliferative activities, the human promonocytic U937 cells were used. Berberine exhibited dose-dependent antiproliferative effects. Morphological evidence of apoptosis, including apoptotic DNA fragmentation, were observed in cells treated with 75 microg ml(-1) of berberine for 24h. Flow cytometry analysis revealed that berberine had no effect on cell cycle profile of U937 cells, however, sub-G(0) fraction (apoptotic cell population) was detected. The percentage of sub-G(0) fraction of cells treated with 75 microg ml(-1) of berberine was 25.3+/-1.6%. Berberine induces significant changes in mitochondrial membrane potential of U937 cells. The highest tested concentration of berberine decreased the mitochondrial membrane potential to 15.8+/-2.4% of control. Additionally, berberine-treated cells had an elevated level of ROS production. Activation of caspase-9 and caspase-3 was also detected, with no caspase-8 activation observed. Taken together, the results clearly demonstrate that berberine induces apoptosis of U937 cells through the mitochondrial/caspase-dependent pathway.     

Galangin induces apoptosis in hepatocellular carcinoma cells through the caspase 8/t-Bid mitochondrial pathway

This study has investigated whether galangin, a flavonol derived from Alpinia officinarum Hance and used as food additives in southern China, induces apoptosis in hepatocellular carcinoma cells (HCCs) by activation of the caspase-8 and Bid pathway. The apoptosis of HCCs was evaluated by in situ uptake of propidium iodide and Hoechst 33258. Protein expressions were detected by Western blotting. Caspase-8 activity was measured using colorimetric method. To confirm the galangin-induced apoptotic pathway, inhibition of caspase-8 activity by Z-IETD-FMK, knockdown of Bid expression with siRNA, and overexpression of Bcl-2 in cells were carried out, respectively. The results show that galangin has significantly induced apoptosis in HCC lines. The caspase-8 is activated, and the cleavage of Bid results in the increase in tBid. The galangin-induced apoptosis is attenuated by Z-IETD-FMK, Bid siRNA, and Bcl-2 overexpression, respectively. However, Bcl-2 fails to suppress caspase-8 activation and the cleavage of Bid. This study has demonstrated that galangin induces apoptosis in HCCs by activating caspase 8/t-Bid mitochondrial pathway. Although Bcl-2 overexpression attenuates galangin-mediated apoptosis of HCCs, it is not mediated by the inhibition of tBid generation and caspase-8 activation.     

Galangin induces apoptosis in hepatocellular carcinoma cells through the caspase 8/t-Bid mitochondrial pathway

This study has investigated whether galangin, a flavonol derived from Alpinia officinarum Hance and used as food additives in southern China, induces apoptosis in hepatocellular carcinoma cells (HCCs) by activation of the caspase-8 and Bid pathway. The apoptosis of HCCs was evaluated by in situ uptake of propidium iodide and Hoechst 33258. Protein expressions were detected by Western blotting. Caspase-8 activity was measured using colorimetric method. To confirm the galangin-induced apoptotic pathway, inhibition of caspase-8 activity by Z-IETD-FMK, knockdown of Bid expression with siRNA, and overexpression of Bcl-2 in cells were carried out, respectively. The results show that galangin has significantly induced apoptosis in HCC lines. The caspase-8 is activated, and the cleavage of Bid results in the increase in tBid. The galangin-induced apoptosis is attenuated by Z-IETD-FMK, Bid siRNA, and Bcl-2 overexpression, respectively. However, Bcl-2 fails to suppress caspase-8 activation and the cleavage of Bid. This study has demonstrated that galangin induces apoptosis in HCCs by activating caspase 8/t-Bid mitochondrial pathway. Although Bcl-2 overexpression attenuates galangin-mediated apoptosis of HCCs, it is not mediated by the inhibition of tBid generation and caspase-8 activation.     

Methyl methanesulfonate and hydrogen peroxide differentially regulate p53 accumulation in hepatoblastoma cells.

Genotoxic chemicals not only damage cellular DNA, but may also induce cell apoptosis if they are lethal to the cell. p53, Bcl-2 and Bax play important roles in the regulation of genotoxic chemical induced cell apoptosis. Since the mechanisms by which cellular DNA damaged by different DNA-damaging chemicals may not be the same, we studied the involvement of p53, Bcl-2 and Bax in apoptosis induced by methyl methanesulfonate (MMS) and hydrogen peroxide (H2O2). H2O2 damages DNA by free radical generation and MMS damages DNA by DNA methylation. At non-lethal doses, both H2O2 and MMS induced high level of p53 protein accumulation. Nevertheless, while the amount of p53 protein increased with the dose of MMS and the occurrence of apoptotic cell death events, H2O2 doses that induce cell apoptosis attenuated the p53 protein accumulation level. Lethal MMS treatment also increased Bax, but not Bcl-2 expression, whereas in H2O2 induced apoptosis, the level of both Bcl-2 and Bax declined. These results indicate that toxic chemicals differentially regulate the accumulation of p53 protein. Thus, the pathways of toxic chemicals induced cell apoptosis are different and independent.     

Glycoborinine induces apoptosis through mitochondrial pathway in HepG2 cells

Glycoborinine (GB), a natural carbazole alkaloid isolated from Glycosmis pentaphylla, has been shown to be a potential molecule against cancer cells. In this study, the cell-signaling pathway of its anti-tumor activity was investigated. MTT assay result showed that GB inhibited HepG2 cell proliferation in a dose- and time-dependent manner and 50% inhibiting concentration (IC₅₀) of GB-induced cell death was 39.7 μM for a period of 48 h. GB-induced HepG2 apoptosis was confirmed by Hochest 33258 staining and PI staining. The level of reactive oxygen species (ROS) was measured with H₂DCF-DA staining and the change of mitochondrial membrane potential (△Ψ^m) was analyzed with tetrechloro-tetraethylbenzimidazolcarbocyanine iodide (JC-1) probe. Results showed that GB at 12.5, 25, and 50 μM promoted ROS production. GB induced HepG2 apoptosis through a mitochondrial apoptotic pathway, which was demonstrated by GB-induced increase in the ratio of Bax/Bcl-2, cytochrome C release, the ratio of cleaved caspase-3/procaspase-3, and the ratio of cleaved poly ADP-ribose polymerase (cleaved PARP)/poly ADP-ribose polymerase (PARP). To summarize, this study demonstrated that GB could induce HepG2 apoptosis through the mitochondrial-dependent pathway, which might provide a promising approach to cure liver cancer with GB.     

天然活性分子isatin经p53介导的线粒体途径诱导乳腺癌细胞MCF-7凋亡

目的探讨吲哚醌(isatin)对乳腺癌细胞MCF-7的抗肿瘤作用及其具体的调控机制。方法不同浓度isatin(0、50、100、200μmol·L~(-1))作用于乳腺癌细胞48 h后,利用细胞荧光染色、RT-PCR、Western blot及流式细胞术等方法检测isatin的促凋亡作用。结果不同浓度isatin处理MCF-7细胞48 h,荧光显微镜观察到细胞出现核染色质聚集、细胞体积缩小及DNA断裂等典型的凋亡形态学改变。RT-PCR和Western blot结果证实,随着isatin浓度的不断增加,p53、Bax mRNA和蛋白表达量也逐渐增加,而Bcl-2 mRNA及蛋白表达下降;流式细胞仪结果提示不同药物浓度作用的细胞膜电位出现不同程度的下降,caspase-9被激活。Western blot结果显示isatin处理组细胞胞质细胞色素C含量明显增加,相反线粒体中细胞色素C含量相应降低。结论 isatin具有明显诱导乳腺癌细胞MCF-7凋亡的作用,其可能的作用机制是经p53的线粒体凋亡通路被激活。     

AlCl3 induces lymphocyte apoptosis in rats through the mitochondria–caspase dependent pathway

To investigate apoptosis mechanisms in lymphocytes induced by aluminum trichloride (AlCl₃) through the mitochondria–caspase dependent pathway, the spleen lymphocytes of rats were cultured with RPMI‐1640 medium and exposed to AlCl₃·6H₂O in the final concentrations of 0 (control group, CG), 0.3 (low‐dose group, LG), 0.6 (mid‐dose group, MG), and 1.2 (high‐dose group, HG) mmol·L^?1 for 24 h, respectively. Mitochondrial transmembrane potential (ΔΨm), cytochrome C (Cyt C) protein expression in cytoplasm, Caspase‐3 and Caspase‐9 activity, Bcl‐2, Bax, Caspase‐3 and Caspase‐9 mRNA expressions, DNA ladder and lymphocytes apoptosis index were detected. The results showed that Cyt C protein expression in cytoplasm, Caspase‐3 and Caspase‐9 activity, Bcl‐2, Bax, Caspase‐3 and Caspase‐9 mRNA expressions, the ratio of Bcl‐2 and Bax mRNA expression, lymphocytes apoptosis index increased, while ΔΨm decreased in the AlCl₃‐treated groups compared with those in CG. The results indicate that AlCl₃ induces lymphocyte apoptosis in rats through the mitochondria–caspase dependent pathway. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 385–394, 2016.     

Methotrexate induces apoptosis through p53/p21-dependent pathway and increases E-cadherin expression through downregulation of HDAC/EZH2

Methotrexate (MTX) is a dihydrofolate reductase (DHFR) inhibitor widely used as an anticancer drug in different kinds of human cancers. Here we investigated the anti-tumor mechanism of MTX against non-small cell lung cancer (NSCLC) A549 cells. MTX not only inhibited in vitro cell growth via induction of apoptosis, but also inhibited tumor formation in animal xenograft model. RNase protection assay (RPA) and RT-PCR demonstrated its induction of p53 target genes including DR5, p21, Puma and Noxa. Moreover, MTX promoted p53 phosphorylation at Ser15 and acetylaion at Lys373/382, which increase its stability and expression. The apoptosis and inhibition of cell viability induced by MTX were dependent on p53 and, partially, on p21. In addition, MTX also increased E-cadherin expression through inhibition of histone deacetylase (HDAC) activity and downregulation of polycomb group protein enhancer of zeste homologue 2 (EZH2). Therefore, the anticancer mechanism of MTX acts through initiation of p53-dependent apoptosis and restoration of E-cadherin expression by downregulation of HDAC/EZH2.     

Diosgenin induces apoptosis in HeLa cells via activation of caspase pathway

AIM: To investigate the mechanism of diosgenin-induced HeLa cell apoptosis. METHODS: HeLa cell growth was measured by MTT method. Apoptosis was detected by electron microscopy and agarose gel electrophoresis. Ratio of apoptotic cells was measured by APO-BRDU kit. Cell cycle distribution and changes of mitochondrial membrane potential were monitored by flow cytometry. Caspase activities were assayed by caspase apoptosis detection kit. Western blot analysis was used to evaluate the level of mitochondrial Bcl-2 expression. RESULTS: Diosgenin inhibited HeLa cell growth. HeLa cells treated with diosgenin showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. Caspase family inhibitor (z-VAD-fmk), caspase-9 inhibitor (Ac-AAVALPAVLLALLAPLEHD-CHO), and caspase-3 inhibitor (z-DEVD-fmk) partially prevented diosgenin-induced apoptosis, but not caspase-8 inhibitor (z-IETD-fmk) and caspase-10 inhibitor (z-AEVD-fmk). Diosgenin caused reduction of mitochondrial membrane po     

托瑞米芬联合顺铂对p53缺失型肺癌细胞株H1299生长抑制作用的研究

目的 探讨托瑞米芬联合顺铂对人肺癌细胞株H1299细胞生长抑制作用及其机制,了解P糖蛋白在H1299细胞中的表达情况.方法 本研究设空白组、对照组(单细胞悬液100μl)、实验组(单细胞悬液100μl+不同药物及浓度),实验组又分为托瑞米芬、顺铂和该2种药物联合组.用四甲基偶氮唑兰比色法检测托瑞米芬及与顺铂联用后H1299细胞的细胞增殖抑制率,分析其细胞周期的变化,检测P糖蛋白在H1299中的表达.结果 托瑞米芬的浓度为20和40 μmol/L时的细胞增殖抑制率分别为(0.307±0.011)％和(0.634±0.007)％,与对照组(0.068 ±0.031)％比较,组间差异均有统计学意义(P＜0.01).低剂量的托瑞米芬(5、10 μmol/L)联合不同浓度顺铂后的细胞增殖抑制率均高于单用顺铂组,并呈现浓度依赖性,组间比较差异有统计学意义(P＜0.05).托瑞米芬与顺铂联用促进H1299细胞凋亡,呈现浓度依赖性.托瑞米芬与顺铂联用后,与单用顺铂组相比,H1299细胞周期发生明显变化,G0/G1期比例增加,S期细胞比例下降,检测出44.9％的H1299细胞有P糖蛋白的存在.结论 低浓度的托瑞米芬(5、10μmol/L)与顺铂联用对H1299细胞有明显的协同抗肿瘤效应,其机制可能与抑制细胞增殖、改变细胞周期分布、促进细胞凋亡有关,且这种作用不依赖于p53基因和雌激素受体.     

Supernatant of bacterial fermented soybean induces apoptosis of human hepatocellular carcinoma Hep 3B cells via activation of caspase 8 and mitochondria.

SC-1, the aqueous phase of soybean fermentation products by bacteria (Bacillus subtilis and Bacillus brevis), significantly inhibited the growth and clonogenesity of human hepatocellular (Hep 3B), mouse hepatocellular (ML-1), and human colorectal (HCT 116 and HT-29) carcinoma cells. Cytotoxicity of SC-1 in Hep 3B cells was through the process of apoptosis characterizing by increase in cell population of sub-G(1) phase, fragmentation of DNA, and change of nuclear morphology. Treatment of Hep 3B cells with SC-1 activated caspase 8 and caspase 3. Elevation of nuclear DNA fragmentation factor 40 (DFF40) and cleavage form of poly(ADP-ribose) polymerase (PARP) were also observed. SC-1 also activated intrinsic pathway via increase of pro-apoptotic (tBid, Bak and Bax) and decrease of anti-apoptotic (Bcl-2 and Bcl-x(L)) proteins on mitochondria, disruption of mitochondrial membrane potential, release of cytochrome c and Smac (second mitochondria-derived activator of caspase/direct IAP binding protein with low PI) from mitochondria, and activation of caspase 9. Inhibition on protein expression of Ku70 in cytosol and cyclooxygenase (COX)-2, but not COX-1, in whole cell lystes were revealed in SC-1-treated Hep 3B cells. These results suggest caspase 8, Ku70 and mitochondria are involved in the antitumor mechanism of SC-1 in Hep 3B cells.     

Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways

Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment.     

A new semisynthetic 1-O-acetyl-6-O-lauroylbritannilactone induces apoptosis of human laryngocarcinoma cells through p53-dependent pathway

Initiation of apoptosis is an important event for chemoprevention and chemotherapy of cancer. Naturally derived products had drawn growing attention as lead compounds for anticancer drug discovery. ABL-L, a semisynthetic analogue of natural sesquiterpenoid 1-O-acetylbritannilactone (ABL) isolated from Inula britannica, showed stronger suppression against three solid tumor cell lines with 4–10 fold improvement than ABL. However, its molecular mechanism of cell death induction has still not been determined. The present study evaluated the anticancer efficacy of ABL-L and its biological activities mechanism on human laryngocarcinoma cells HEp-2 in vitro. We found that ABL-L-induced inhibition of cell proliferation was associated with an increase in G1-phase arrest. Typical apoptotic morphological and biochemical features were also observed in treated cells. Furthermore, the levels of the anti-apoptotic Bcl-2, pro-caspase 3/8/9 and poly(ADP-ribose) polymerase PARP decreased, and the level of pro-apoptotic Bax increased. Involvement of the caspase-mediated apoptosis was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. In addition, ABL-L induced a tumor suppressor p53 and its target genes expression p21, fas, noxa and puma. The results of p53 knockdown suggest that caspase-mediated apoptosis induced by ABL-L was in p53-dependent pathway on HEp-2 cells. Our data indicate that the cytotoxicity of the novel semisynthetic analogue ABL-L involved G1 cell cycle arrest and apoptosis via a p53-dependent, caspase-mediated pathway on human laryngocarcinoma cells.     

Perfluorooctanoic acid induces apoptosis through the p53-dependent mitochondrial pathway in human hepatic cells: A proteomic study

Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated compounds, and exposure to it has been associated with a number of adverse health effects. However, the molecular mechanisms involved in PFOA toxicity are still not well characterized. In the present study, flow cytometry analysis revealed that PFOA induced oxidative stress, cell cycle arrest and apoptosis in human non-tumor hepatic cells (L-02). Furthermore, we investigated the alterations in protein profile within L-02 cells exposed to PFOA, aiming to explore the mechanisms underlying PFOA hepatotoxicity on the proteome level. Of the 28 proteins showing significant differential expression in response to PFOA, 24 were down-regulated and 4 were up-regulated. This proteomic study proposed that the inhibition of some proteins, including GRP78, HSP27, CTSD and hnRNPC may be involved in the activation of p53, which consequently triggered the apoptotic process in L-02 cells. Induction of apoptosis via the p53-dependent mitochondrial pathway is further suggested as one of the key toxicological events occurring in L-02 cells under PFOA stress. We hope these data will shed new light on the molecular mechanisms responsible for PFOA-mediated toxicity in human liver cells, and from such studies useful biomarkers indicative of PFOA exposure could be developed.