组蛋白去乙酰化酶抑制剂FK228通过阻断Hsp90功能杀伤乳腺癌MCF-7细胞

背景与目的：雌激素受体α（estrogen receptor α,ERα）与乳腺癌发生,发展及耐药密切相关,促进ERα降解可能成为解决乳腺癌耐药的一种新策略.本研究旨在观察组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitor,HDACi）FK228对乳腺癌MCF-7细胞系ERα的清除作用,并对其抗肿瘤作用机制进行深入研究.方法：MTF比色法测定FK228对MCF-7细胞杀伤的剂量-时间-效应关系;流式细胞仪分析细胞周期的改变;蛋白印迹及免疫共沉淀实验检测细胞内蛋白表达水平及翻译后修饰的变化.结果：FK228呈时间依赖性杀伤MCF-7细胞,阻断细胞周期于G2/M期,增强Hsp90乙酰化修饰,清除ERα及其他Hsp90底物蛋白,阻断Ras/Raf/MEK/ERK及PI3K/Akt信号通路,诱导细胞凋亡.结论：FK228通过乙酰化修饰影响Hsp90分子伴侣功能,介导ERα及其他Hsp90底物蛋白降解是其有效杀伤乳腺癌细胞的分子机制.FK228有可能成为乳腺癌治疗的新型药物.     

PI3K/AKT信号通路阻断药联合小檗碱对前列腺癌DU145细胞生长的抑制作用

目的 探讨采用磷脂酰肌醇3-激酶(PI3K)抑制药——LY294002抑制磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶(PI3K/AKT)信号通路联合小檗碱对前列腺癌DU145细胞生长的抑制作用.方法 采用MTT法检测细胞增殖情况;采用流式细胞仪检测细胞凋亡率和细胞周期分布情况;采用Western blot检测细胞中PI3K、p-AKT、cyclin D1、bcl-2、BAX蛋白表达情况.结果 随着小檗碱作用浓度的增加,DU145细胞的增殖率逐渐降低;不同浓度小檗碱与LY294002联合处理对DU145细胞增殖的抑制作用均较相同浓度小檗碱单独处理增强(P﹤0.05).与空白对照组相比,小檗碱组DU145细胞的凋亡率增高(P﹤0.05),G0/G1期细胞所占比例增高(P﹤0.05),PI3K、p-AKT、cyclin D1、bcl-2蛋白表达水平均下调(P﹤0.05),BAX蛋白表达水平上调(P﹤0.05).与小檗碱组和空白对照组相比,小檗碱+LY294002组DU145细胞的凋亡率增高(P﹤0.05),G0/G1期细胞所占比例增高(P﹤0.05),PI3K、p-AKT、cyclin D1、bcl-2蛋白表达水平均下调(P﹤0.05),BAX蛋白表达水平上调(P﹤0.05).结论 小檗碱能够抑制DU145细胞增殖,并促进细胞凋亡和细胞周期阻滞,采用LY294002阻断PI3K/AKT信号通路能够明显增强小檗碱对前列腺癌DU145细胞生长的抑制作用.     

MMC诱导EJ细胞凋亡和Fas/FasL、Caspase-3基因表达

目的；研究丝裂霉素（MMC）在体外诱导膀胱癌细胞EJ凋亡和凋亡相关基因Fas/FasL,Caspas-3表达的关系。方法：以低剂量MMC（0.100mg/ml)诱导EJ细胞凋亡；以TUNEL法和FCM研究EJ细胞凋亡，细胞周期分布及Caspase-3抗体对抗MMC诱导凋亡；以免疫组化检测Fas/FasL,Caspas-3蛋白表达。结果：低剂量MMC处理的EJ细胞出现明显的凋亡形态特征，凋亡峰和细胞生长阻滞均发生于G0／G1期，Fas/FasL,Caspas-3蛋白呈上调表达，Caspase-3抗体能特异性阻断MMC诱导EJ细胞凋亡。结论；低剂量MMC能够诱导EJ细胞凋亡和增加Fas/FasL,Caspas-3基因表达，且与启动Caspase凋亡信号传导有关。     

曲古菌素A诱导前列腺癌DU-145细胞有丝分裂的灾变

目的：研究组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitor,HDACi）曲古菌素（trichostatina A,TSA）对前列腺癌DU145细胞有丝分裂的影响,探讨HDACi杀伤肿瘤细胞的新机制。方法：将前列腺癌DC-145细胞分成不加药对照组和不同剂量（100、200、300、400nmol/L）TSA加药组,药物作用一定时间后,MTT法检测TSA对DU145细胞的杀伤效应,瑞氏-姬姆萨染色观察细胞形态的变化,流式细胞术分析细胞周期的改变,免疫荧光染色观察DU145细胞异常的有丝分裂现象,Western blotting检测TSA处理对DU145细胞某些调控蛋白表达的影响。结果：TSA处理诱导DU145细胞发生有丝分裂,TSA处理24h后多核细胞数目由0.24%增加至1.21%。细胞周期计数结果显示,TSA处理后有丝分裂各期细胞比例发生明显改变,表现为有丝分裂前中期细胞所占比例增加,后末期细胞所占比例减少。免疫荧光染色显示,细胞出现多极纺锤体、染色体分离滞后等异常有丝分裂现象。TSA作用于DU145细胞后,能明显抑制Survivin蛋白的表达,增强细胞骨架蛋白Tubulin的乙酰化,并诱导P21蛋白高表达。结论：TSA能够诱使DU145细胞发生有丝分裂灾变,其机制可能与TSA降低Survivin蛋白的表达以及增强微管蛋白的乙酰化有关。     

组蛋白去乙酰化酶抑制剂MS-275对人骨髓瘤U266细胞生长的影响及其可能机制

目的 探讨组蛋白去乙酰化酶抑制剂(HDACi)MS-275对人骨髓瘤细胞U266的凋亡抑制基因生存素(survivin)和核因子-κB(NF-κB)表达的影响.方法 台盼蓝拒染法观察MS-275对细胞活力的影响;瑞氏-姬姆萨染色观察细胞形态学变化;流式细胞仪分析细胞周期;Western blot检测survivin、p21、细胞周期依赖激酶4(CDK4)和NF-κB的抑制蛋白(IKB-α)等的表达,以及凋亡信号通路中caspase-3活化及蛋白聚ADP核糖聚合酶(PARP)裂解情况.结果 MS-275抑制U266细胞增殖,阻断细胞周期于G0/G1期,呈时间-剂量依赖性.MS-275作用U266细胞48 h的IC50为1.39μmol/L.2 μmol/L MS-275作用U266细胞24 h后,G0/G1期细胞所占比例为(64.57±4.09)%;作用36 h后,G0/G1期细胞所占比例为(87.20±2.83)%;瑞氏-姬姆萨染色显示,U266细胞形态发生明显变化.Western blot检测表明,MS-275作用U266细胞后,survivin和CDK4表达下降,p21表达增加,IκB-α磷酸化水平受到明显抑制,caspase-3被裂解活化,其底物蛋白PARP发生剪切,细胞发生凋亡.结论 MS-275可诱导人骨髓瘤细胞系U266凋亡,NF-κB信号通路阻断是凋亡发生的机制之一.     

丁酸钠对前列腺癌LNCaP细胞HER-2信号通路的影响

 目的 研究组蛋白去乙酰化酶抑制剂丁酸钠对前列腺癌LNCaP细胞HER 2信号通路的影响，探讨其抗肿瘤作用的分子机制。方法 四甲基偶氮唑蓝(MTT)检测药物对肿瘤细胞增殖的影响；hoechst 33342染色观察细胞凋亡的形态学变化，Western blot检测凋亡标志蛋白、HER2/ neu、Phos Akt、Phos Erk等信号蛋白的表达。结果 丁酸钠能够有效抑制LNCaP细胞的增殖并诱导细胞凋亡，半效杀伤剂量（EC50）为5.6mmol/L；药物能够抑制HER 2基因的转录和蛋白的表达，并抑制下游信号通路中MAPK和AKT的活化。结论 丁酸钠能够阻断对前列腺癌细胞生长具有重要作用的HER 2信号通路，从而对肿瘤细胞发挥抑制作用。     

紫草素对人食管癌TE-1细胞增殖、凋亡和细胞周期的影响及其可能的机制

目的：观察紫草素对人食管癌TE-1细胞增殖、凋亡和细胞周期的影响,并探究其作用机制。方法：采用不同浓度的 紫草素（0、 1、 5、 10 μmol/L）处理TE-1细胞,MTT法检测24、 48、 72 h后各组细胞增殖水平;紫草素处理各组TE-1细胞48 h后,采用 Hoechst 33258荧光染色观察细胞凋亡状况,流式细胞术检测细胞的凋亡水平及周期变化,Western blotting检测TRAP1/Akt/ mTOR信号通路相关蛋白表达变化。结果：紫草素呈时间和浓度依赖性抑制TE-1细胞增殖（P<0.05或P<0.01）;与对照组相比, 紫草素能显著促进TE-1细胞凋亡（P<0.01）, 使TE-1细胞周期发生G0/G1期阻滞（P<0.05或P<0.01）,同时降低TRAP1、p-Akt以及 p-mTOR表达水平（P<0.05或P<0.01）,以上作用具有剂量依赖性。结论：紫草素能显著抑制TE-1细胞的增殖,诱导细胞发生G0/ G1期阻滞并促进其凋亡,这可能与其抑制TRAP1/Akt/mTOR信号通路有关。     

PI3K／Akt／inTOR信号传导通路与恶性肿瘤浸润和转移的研究进展

PI3K／Akt／mTOR信号通路作为细胞内重要信号传导通路之一,通过影响下游多种效应分子的活化状态,在细胞内发挥着抑制凋亡、促进增殖的关键作用,它与人类多种肿瘤的发生发展密切相关。本文综述了PI3K／Akt／mTOR信号通路的组成与功能、调节以及其抗肿瘤细胞凋亡作用机理等方面的研究进展,并就其抗细胞凋亡作用在肿瘤治疗中的应用作了评述,期待为以PI3K／Akt／mTOR信号通路中关键分子为靶点的肿瘤治疗研究提供参考。     

岩舒注射液诱导胃癌SGC-7901细胞凋亡及其机制

目的：探讨岩舒注射液（复方苦参注射液）对体外培养人胃癌细胞株SGC7901的生长抑制和诱导凋亡作用。方法：采用MTT法检测岩舒注射液对SGC-7901细胞的生长押制作用；Annexin V-FITC＋PI双参双数检测细胞凋亡；流式细胞仪测定经不同浓度岩舒注射液处理后SGC-7901细胞周期、Fas、Bcl-2蛋白表达及其线粒体膜电位。结果：岩舒注射液对SGC-7901细胞生长有抑制作用，并呈剂量-效应关系，P〈0．01。其48h IC50值为7／200原液稀释浓度；SGC-7901细胞经岩舒注射液处理后可发生凋亡；岩舒注射液使细胞周期阻滞于G0／G1期（P〈O．01），但对于Fas、Bcl-2蛋白表达无影响；可降低线粒体膜电位（P〈0．01）。结论：岩舒注射液对人胃癌SGC-7901细胞有生长抑制和诱导凋亡作用，其诱导凋亡机制可能与细胞周期阻滞、抑制肿瘤细胞增殖、线粒体膜电位降低有关。     

香加皮杠柳苷通过抑制Wnt／β-catenin信号通路诱导结肠癌细胞SW480凋亡

背景与目的：Wnt／β-catenin信号通路在人类肿瘤尤其在大肠癌的发生发展中起着重要作用。本研究分析了香加皮杠柳苷（periplocin extracted fromcortex periplocae,CPP）对人结肠癌细胞SW480增殖的抑制作用,及对Wnt／β-catenin信号通路的调控作用。方法：MTT法检测CPP对SW480细胞增殖的影响,流式细胞技术检测细胞周期的变化和凋亡。Western blot法检测CPP处理组与对照组细胞总蛋白、细胞浆蛋白及细胞核蛋白中β-catenin表达变化,电泳迁移率改变法分析CPP作用后SW480细胞核TCF复合物与其特异性DNA结合序列结合能力变化。半定量RT—PCR法检测CPP作用后细胞中β-catenin、survivin、c—myc和cyclin D1mRNA的表达。结果：CPP明显抑制SW480细胞增殖（P〈0．01）,并呈时间和浓度依赖性;0．5μg／mLCPP可将SW480细胞阻滞于G0／G1期,并诱导细胞凋亡（P〈0．05）。CPP作用后SW480细胞总蛋白、胞浆蛋白及细胞核蛋白中的B—catenin表达均明显降低（P〈0．01）,细胞核中TCF复合物与其特异性DNA结合序列结合能力受到抑制,其下游靶基因mRNA表达水平下降（P〈0．01）,而β-cateninmRNA表达未见明显改变。结论：CPP可明显抑制SW480细胞增殖并诱导细胞凋亡,其作用机制与抑制细胞Wnt／β-catenin信号转导通路有关。     

Low concentrations of the histone deacetylase inhibitor, depsipeptide, enhance the effects of gemcitabine and docetaxel in hormone refractory prostate cancer cells

Histone deacetylase inhibitors (HDACis) have been developed as a new type of drug for cancer treatment. In this study, we examine the augmentation efficacy of depsipeptide (FK228) in combination with gemcitabine (GEM) or docetaxel (DOC) in vitro and in vivo against hormone refractory prostate cancer (HRPC). The anti-proliferative effects, cell cycle distribution and apoptotic status were assessed in HRPC DU145 cells treated with these agents. The in vivo anti-tumor effects of the combination therapy with FK228 and GEM were further evaluated in the DU145 xenografts. FK228 induced a substantial acetylation of the histone proteins even at a low concentration of IC20 (0.56 ng/ml for 48 h treatment), while no effects on the cell cycle arrest and apoptosis induction were observed at the low concentration level. The pretreatment of cells with the IC20 dose of FK228 enhanced the cytotoxicity of both chemotherapeutic agents although the augmentation was more profoundly observed in GEM than DOC. The effects of the FK228 pretreatment were also observed in the in vivo experiment. The mean tumor doubling-time in the FK228 pretreatment combined with GEM was two times longer than that of the monotherapy with FK228 or GEM (p<0.001). These results show that pretreatment with low-dose FK228 enhances the chemosensitivity of DU145 tumors to GEM in vivo, suggesting the therapeutic potential of a new combination of HDACis and conventional chemotherapeutic agents. Further studies are required in order to assess the efficacy of this combination regimen in HRPCs in general.     

地塞米松对前列腺癌DU145细胞ERK1/2活性和cyclin D1表达的影响

目的: 〖HT5"SS〗 探讨糖皮质激素地塞米松抑制雄激素非依赖性前列腺癌细胞DU145的机制。〖HT5W〗方法: 〖HT5"SS〗通过细胞培养方法观察地塞米松及其受体阻断剂RU486对前列腺癌DU145细胞增殖的作用;采用流式细胞仪测定地塞米松对DU145细胞细胞周期的影响;利用Western blot技术检测DU145细胞受地塞米松作用后cyclin D1表达水平和ERK1/2活性的变化;用RTPCR技术检测DU145细胞中糖皮质激素受体mRNA的表达。〖HT5W〗结果: 〖HT5"SS〗 地塞米松明显抑制DU145细胞的增殖,并且有剂量依赖效应;地塞米松使细胞周期阻滞于G0/G1期。Western blot结果显示,地塞米松作用DU145细胞3 d后,细胞内ERK1/2的活性降低,cyclin D1表达量下降。RU486可以拮抗地塞米松对DU145细胞的作用效果。RTPCR结果显示DU145细胞有糖皮质激素受体mRNA的表达。〖HT5W〗结论: 〖HT5"SS〗地塞米松具有抑制前列腺癌DU145细胞增殖和阻滞细胞周期的作用,此作用与其降低ERK1/2活性、抑制cyclin D1合成有关,提示糖皮质激素对前列腺癌的治疗有重要意义。     

Modulation of p53, ErbB1, ErbB2, and Raf-1 expression in lung cancer cells by depsipeptide FR901228

BACKGROUND: Histone deacetylases (HDACs) modulate chromatin structure by regulating acetylation of core histone proteins. HDAC inhibitors, such as depsipeptide FR901228 (FK228), induce growth arrest and apoptosis in a variety of human cancer cells by mechanisms that cannot be attributed solely to histone acetylation. This study evaluated the mechanisms by which FK228 mediates apoptosis in non-small-cell lung cancer (NSCLC) cells. METHODS: Proliferation and apoptosis were assessed in a panel of NSCLC cell lines that vary in the expression of the growth-regulating proteins p53, pRb, and K-Ras treated with a clinically relevant dose of FK228 (25 ng/mL). Western blot and immunoprecipitation techniques were used to analyze expression of cell-cycle proteins (cyclin A, cyclin E, p53, and p21), signaling-related proteins (ErbB1, ErbB2, and Raf-1), activity of extracellular signal-regulated kinase 1 and 2 (ERK1/2), binding of mutant p53 and Raf-1 to heat shock protein (Hsp)90, and acetylation of Hsp90. RESULTS: FK228 treatment inhibited growth and induced apoptosis in NSCLC cells expressing wild-type or mutant p53. FK228 treatment led to altered expression of cyclin A, cyclin E, and p21, and to reduced expression of mutant, but not wild-type, p53. FK228-treated cells also were depleted of ErbB1, ErbB2, and Raf-1 proteins, and exhibited lower ERK1/2 activity. FK228 treatment also inhibited the binding of mutant p53 and Raf-1 to Hsp90; this inhibition was associated with acetylation of Hsp90. CONCLUSIONS: FK228 depletes the levels of several oncoproteins that are normally stabilized by binding to Hsp90 in cancer cells. The resulting ability of FK228 to diminish signal transduction via pathways involving Raf-1 and ERK may contribute to the potency and specificity of this novel antitumor agent.     

Antiproliferative effects of AVN944, a novel inosine 5-monophosphate dehydrogenase inhibitor, in prostate cancer cells

Inosine 5-monophosphate dehydrogenase II, a key enzyme in the de novo synthesis of purine nucleotides, is expressed in prostate tumors and prostate cancer cells. AVN944 is a new, specific, noncompetitive IMPDH inhibitor. In this study, we investigated the effects of IMPDH inhibitor AVN944 on LNCaP, CWR22Rv1, DU145 and PC-3 human prostate cancer cells. AVN944 inhibited proliferation of these 4 prostate cancer cell lines and was associated with cell cycle G1 arrest of LNCaP cells and S-phase block of androgen-independent CWR22Rv1, DU145 and PC-3 cells. AVN944 induced caspase-dependentand caspase-independent cell death in LNCaP, CWR22Rv1, and DU145 cells. AVN944 induced expression of p53-target proteins Bok, Bax and Noxa in androgen-responsive cell lines and suppressed expression of survivin in prostate cancer cells regardless of their androgen sensitivity. AVN944 also induced differentiation of androgen-independent prostate cancer cells as indicated by morphological changes and increased expression of genes coding for prostasomal proteins, keratins and other proteins, including tumor suppressor genes MIG-6 and NDRG1. AVN944-differentiated androgen-independent DU145 and PC-3 cells are sensitized to TRAIL-induced apoptosis as demonstrated by induction of caspases and PARP cleavage. In summary, AVN944 inhibited the growth of human prostate cancer cells by inducing cell cycle arrest, cell death as well as differentiation. AVN944 is a novel, promising therapeutic agent that might be combined with other agents for treatment of human prostate cancer.     

MLN4924对紫杉醇耐药的前列腺癌细胞增殖和凋亡的影响

目的:研究MLN4924对紫杉醇耐药的前列腺癌细胞增殖和凋亡的影响,从而为紫杉醇耐药前列腺癌的临床治疗提供新的理论依据。方法:不同浓度的MLN4924作用紫杉醇耐药的前列腺癌细胞PC3-TxR和DU145-TxR 48和72小时后,采用MTS检测细胞活力。Western blot检测凋亡相关蛋白Caspase-3、CDT1、p27以及EMT标志物水平。结果:MLN4924能够显著抑制PC3-TxR和DU145-TxR细胞的增殖,并且具有时间和浓度的依懒性。Western blot结果显示MLN4924作用后显著增加细胞内凋亡相关蛋白Caspase-3、CDT1和p27的表达。结论:MLN4924能够显著抑制紫杉醇耐药的前列腺癌细胞增殖、促进细胞凋亡,其相关机制为MLN4924可通过上调p27蛋白表达促进紫杉醇耐药的前列腺癌细胞凋亡。     

Critical role of the c-JunNH2-terminal kinase and p38 mitogen-activated protein kinase pathways on sodium butyrate-induced apoptosis in DU145 human prostate cancer cells.

Sodium butyrate (NaBu) is known to exhibit anti-cancer effects via the differentiation and apoptosis of various carcinoma cells. However, the mechanism by which NaBu induces apoptosis and the involvement of protein kinases during apoptosis is not completely understood. To investigate the underlying pathways, we performed cell culture experiments in androgen-independent human prostate cancer (DU145 cells) focusing on various protein kinases. NaBu causes concentration-dependent cell detachment and growth inhibition. Exposure of DU145 cells to NaBu for 24 h caused a strong apoptotic effect with 26% nuclear fragmentation and condensation. In addition, NaBu induced caspase-3 and poly-ADP ribose polymerase cleavage and up-regulation of bax, suggesting that mitochondrial damage is involved in NaBu-induced caspase-dependent apoptosis. Interestingly, NaBu stimulated p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) activation, but not extracellular signal-regulated kinase 1/2 activation during apoptosis. Furthermore, NaBu up-regulated total protein levels and phospho forms of MAPK kinase 3 (MKK3) and MAPK kinase 4 (MKK4) as the upstream kinases of p38 MAPK and JNK independently of oxidative stress. Taken together, it is suggested that NaBu can be a promising chemopreventive agent for prostate cancer and the p38 MAPK and JNK pathways have critical roles in NaBu-induced apoptosis in DU145 cells.     

Phenethyl isothiocyanate (PEITC) promotes G2/M phase arrest via p53 expression and induces apoptosis through caspase- and mitochondria-dependent signaling pathways in human prostate cancer DU 145 cells

Phenethyl isothiocyanate (PEITC), one of many compounds found in cruciferous vegetables, has been reported as a potential anticancer agent. In earlier studies, PEITC was shown to inhibit cell growth and induction of apoptosis in many cancer cell lines. However, no report has shown whether PEITC can induce apoptosis in human prostate cancer cells. Herein, we aimed to determine whether PEITC has anticancer activity in DU 145 human prostate cancer cells. As a result, we found that PEITC induced a dose-dependent decrease in cell viability through induction of cell apoptosis and cell cycle arrest in the G(2)/M phase of DU 145 cells. PEITC induced morphological changes and DNA damage in DU 145 cells. The induction of G(2)/M phase arrest was mediated by the increase of p53 and WEE1 and it reduced the level of CDC25C protein. The induction of apoptosis was mediated by the activation of caspase-8-, caspase-9- and caspase-3-depedent pathways. Results also showed that PEITC caused mitochondrial dysfunction, increasing the release of cytochrome c and Endo G from mitochondria, and led cell apoptosis through a mitochondria-dependent signaling pathway. This study showed that PEITC might exhibit anticancer activity and become a potent agent for human prostate cancer cells in the future.     

Role of mitogen-activated protein kinases in phenethyl isothiocyanate-induced apoptosis in human prostate cancer cells

The present study was undertaken to examine the role of mitogen-activated protein kinases (MAPKs) in apoptosis induction by phenethyl isothiocyanate (PEITC), a cruciferous vegetable-derived cancer chemopreventive agent, with DU145 and LNCaP human prostate cancer cells as a model. The MAPK family of serine/threonine kinases, including extracellular signal-regulated kinase1/2 (ERK1/2), c-jun N-terminal kinase1/2/3 (JNK1/2/3), and p38 MAPK play an important role in cell proliferation and apoptosis in response to different stimuli. Exposure of DU145 and LNCaP cells to growth suppressive concentrations of PEITC resulted in activation of ERK1/2 and JNKs, but not p38 MAPK, in both cell lines. In DU145 cells, the apoptosis induction by PEITC was statistically significantly attenuated by pharmacological inhibition of JNKs with SP600125. Adenovirus-mediated overexpression of Flag-tagged JNK binding domain (JBD) of JNK-interacting protein-1 (JIP-1), an inhibitor of JNK, also inhibited PEITC-induced apoptosis in DU145 cells. On the other hand, inhibition of ERK1/2 activation with MEK1 inhibitor PD98059 failed to offer protection against PEITC-induced apoptosis in DU145 cells. In LNCaP cells, the PEITC-induced cell death was not affected by either pretreatment with PD98059 or SP600125 or overexpression of JBD of JIP-1. These results indicate that involvement of MAPKs in apoptosis induction by PEITC in human prostate cancer cells is cell line-specific.