甘草酸对小鼠腹腔巨噬细胞泡沫化的影响

目的探讨蛋白激酶C(PKC)信号传导通路对单核细胞趋化蛋白1(MCP-1)诱导的人脐静脉内皮细胞(hUVEC)凋亡的影响。方法培养并鉴定人脐静脉内皮细胞;Ca2+荧光指示剂Fura-2/AM作用细胞,荧光分光光度计检测细胞内Ca2+浓度变化;用不同浓度的PKC激动剂PMA和PKC抑制剂Chelerythrine分别作用人脐静脉内皮细胞后,再用10μg/L的MCP-1诱导,流式细胞术检测细胞凋亡率。结果培养的人脐静脉内皮细胞株经免疫荧光鉴定Ⅷ抗体阳性,证明为内皮细胞;MC....     

三氧化二砷诱导胃癌细胞凋亡机制探讨

目的：研究三氧化二砷(As2O3)对人胃癌细胞凋亡相关基因的影响，探讨其抗肿瘤的作用机制。方法：As2O3作用于体外培养的人胃癌细胞株，运用免疫组化技术检测p53、bcl-2、bax基因编码蛋白。结果：经As2O3作用的人胃癌细胞p53、bcl-2基因表达水平降低，bax基因表达水平增加。结论：As2O3可能通过多种途径诱导胃癌细胞凋亡。     

三氧化二砷诱导胃癌细胞凋亡及其对C-myc和TGF-β1表达的影响

目的 探讨三氧化二砷（As2O3）对体外培养的人胃癌细胞SGC-7901生长的抑制和诱导细胞凋亡的作用。方法 用MTT法检测药物效应，透射电镜及流式细胞仪观察As2O3处理SGC-7901细胞后细胞周期细胞凋亡。细胞免疫化学观察As2O3处理后SGC-7901细胞TGF-β1及C-myc表达的变化。结果 ①MTT法证实As2O3对SGC-7901细胞生长有抑制作用，并呈剂量．效应关系。②流式细胞仪分析As2O3处理SGC-7901细胞后细胞滞留于G2／M期，并可见凋亡峰。③透射电镜可见SGC-7901细胞出现典型的细胞凋亡及坏死形态学改变。④As2O3导致C—myc表达的波动，下调TGF-β1，表达。结论As203对人胃癌细胞SGC-7901有抑制作用，其抑制作用可能通过导致C—myc基因表达波动，诱导胃癌细胞凋亡和坏死、阻抑细胞周期进程，抑制SGC-7901细胞增殖。同时通过下调TGF-β1表达阻止胃癌的恶性进程。     

甲状腺刺激抗体对甲状腺细胞分泌功能影响的信号途径

目的探讨甲状腺刺激抗体(TSAb)对甲状腺细胞分泌功能影响的信号途径。方法选择福建医科大学附属协和医院2003-01~10的Graves病(GD)40例,作为观察组;以院内健康职工40人,作为对照组。应用以酶联免疫吸附法(ELISA)测定蛋白激酶A(PKA)和蛋白激酶C(PKC)活性;应用PKA、PKC激活和抑制剂激活和阻断信号通路;应用放免法检测T3。结果(1)TSAb呈时间剂量依赖性激活甲状腺细胞中的PKA和PKC(P<0.05)。(2)TSAb刺激甲状腺细胞T3分泌的效应与PKA激活剂相似,且可被PKA抑制剂抑制,PKC激活剂佛波酯(TPA)和抑制剂无此效应。TPA可部分抑制TSAb和PKA激活剂刺激的T3分泌。结论TSAb刺激甲状腺细胞T3分泌主要是通过环腺苷酸(cAMP)-PKA途径,PKC途径可影响cAMP-PKA途径而抑制TSAb刺激的T3分泌。     

PKC在细胞凋亡中的作用

引起细胞凋亡的原因较多 ,目前发现蛋白激酶 C(proteinkinase C,PKC)在凋亡发生过程中起着信号传导作用。作为细胞信号传导重要成分的 PKC在细胞的凋亡中起着重要作用。PKC是一个富含丝 /苏氨基酸的激酶 ,由 77～ 2 3Kd的多肽单链构成〔1〕,除在凋亡方面发挥作用外还参与调节神经兴奋性、突触塑形、细胞增生和分化、基因表达及细胞坏死。1　PKC分类与结构根据 PKC结构及特征 ,把它们分成三大类〔1～ 3〕。经典 PKC(CPKC)包括 α、β1 、β2 和 γ四种亚型。新型 PKC(n PKC)包括 δ、ε、η、θ、ξ五种亚型。不典型 PKC(a PK…     

蛋白激酶C及抑制剂在肺癌耐药中的研究进展

耐药已成为当今肺癌化疗过程中的一大难题,其作用机制至今还不十分清楚.蛋白激酶C(protein kinase C,PKC)作为多种信号传导过程中的枢纽,不仅参与细胞信息传递、分泌、细胞分化、增殖,更重要的是参与肿瘤细胞的凋亡和分化.国内外研究表明通过抑制PKC的活性,减少其表达量可以增加细胞内药物的积聚导致胞内有效浓度的上升,从而降低肿瘤细胞耐药率.PKC抑制剂对肿瘤细胞具有明显的诱导分化、增强细胞毒性、促进细胞凋亡的作用.目前已有部分PKC抑制剂进入了临床的Ⅰ/Ⅱ期研究中,并取得了一定的疗效,通过对其作用机制的进一步深入探讨,有望在肺癌耐药的研究中取得更多的突破.     

胃癌细胞中环氧合酶-2对延迟整流性钾通道调控机制的研究

目的 探讨胃癌细胞中环氧合酶(COX)-2对延迟整流性钾通道(HERG)电流的影响和相应的调控机制.方法 ①采用逆转录聚合酶链反应(PCR)、Western印迹和膜片钳技术检测环氧合酶(COX)-2反义载体转染胃癌细胞前后HERG mRNA、蛋白和电流的变化.②采用酶联免疫吸附试验检测COX-2反义载体转染胃癌细胞前后环磷酸腺苷(cAMP)水平的变化.③采用PCR技术构建缺失cAMP结合结构域的HERG突变体,并转染胃癌细胞.④应用COX-2抑制剂和前列腺素(PG)E2作用于胃癌细胞和HERG突变体转染的胃癌细胞,观察HERG电流的变化.⑤将cAMP的拟似剂和拮抗剂、蛋白激酶(PK)A抑制剂分别作用于胃癌细胞和HERG突变体转染的胃癌细胞,观察相应的HERG电流变化.结果 ①与亲本细胞相比,COX-2反义转染胃癌细胞的HERG mRNA和蛋白表达无变化,而HERG电流强度减弱(P<0.05).②与亲本细胞相比,COX-2反义转染胃癌细胞中的cAMP水平明显下降(P<0.05).③COX-2抑制剂减弱而PGE2增强HERG电流的强度.但在缺失cAMP结合域的HERG突变体转染后的胃癌细胞,COX-2抑制剂和PGE2对HERG电流未产生明显的影响.④cAMP拟似剂可增强SGC7901细胞的HERG电流,而cAMP拮抗剂则减弱其电流.但对于缺失cAMP结合结构域的突变体转染的胃癌细胞中的HERG电流,cAMP的拟似剂和拮抗剂均未显示出明显的增强或抑制作用.⑤PKA抑制剂对SGC7901细胞和突变体转染的胃癌细胞的HERG电流均无明显影响.结论 COX-2通过其代谢产物PGE2而影响HERG电流.PGE2通过与受体结合后影响cAMP浓度,而cAMP通过与HERG蛋白上的特殊结构域结合对HERG电流产生影响,此过程不受PKA的调控.     

表没食子儿茶素没食子酸酯诱导细胞凋亡蛋白酶途径依赖的人胃癌细胞株MKN45凋亡

背景：表没食子儿茶素没食于酸酯（EGCG）可诱导人胃癌细胞株MKN45凋亡，但其凋亡信号的传导途径尚不清楚。目的：研究EGCG诱导人胃癌细胞株MKN45凋亡的作用是否通过细胞凋亡蛋白酶（caspsse-3）依赖途径，为其临床应用提供进一步的理论依据。方法：采用四甲摹偶氮唑蓝（MTT）比色法检测EGCG和caspase-3抑制剂z-DEVD-fmk作用后MKN45细胞的存活率：采用Annexin V-FITC＋PI双染色法检测EGCG和caspase-3抑制剂作用后MKN45细胞的凋亡率：采用酶联免疫吸附测定（ELISA）检测EGCG和caspase-3抑制剂作用后MKN45细胞内caspase-3活性的改变。结果：EGCG可诱导MKN45细胞凋亡，且细胞内caspase-3活性显著升高。而caspase-3抑制剂干预后，EGCG抑制MKN45细胞生长的作用明显减弱，细胞凋亡率下降，caspase-3活性显著下降。结论：EGCG可诱导MKN45细胞凋亡，该作用可被caspase-3抑制剂显著抑制，提示EGCG诱导MKN45细胞凋亡的作用是通过caspase-3依赖途径的。     

应用短发夹状RNA研究HBV X 基因表达对三氧化二砷诱导HepG2细胞凋亡特性的影响

目的应用shRNA(短发夹状RNA)介导的RNA干扰研究HBV X基因表达对三氧化二砷(As2O3)诱导HepG2细胞凋亡特性的影响.方法用噻唑蓝(MTT)还原法分析经2.0μmol/L As2O3处理的HepG2细胞和表达HBV X基因的HepG2-X细胞的生长抑制率.以未处理细胞为对照,流式细胞术分析细胞凋亡比和细胞周期,采用Caspase3/cpp32活性比色试剂盒测定As2O3处理后细胞裂解物中Caspase3的活性.应用脂质体介导HBX序列特异性shRNA表达载体pXi-1、pXi-2和序列无关对照pXi-3转染HepG2-X,再次分析细胞凋亡比、细胞周期和Caspase3活性的变化.结果MTT法表明2.0μmol/L As2O3处理36小时具有理想的细胞生长抑制率.As2O3作用后细胞凋亡比明显增高(P＜0.05),G2/M期细胞增多(P＜0.05).不同HBV X基因表达水平的细胞As2O3诱导的细胞凋亡比有统计学差异(P＜0.05),HepG2-X与HepG2比较,其As2O3诱导的细胞凋亡比下降,且细胞裂解物的Caspase3活性下降(P＜0.05),但应用序列特异性shRNA抑制HBV X基因表达后凋亡比和Caspase3活性可再次增高,而作为对照的序列无关的shRNA则无此效应,但这种效应与细胞周期无关.结论As2O3可诱导HepG2细胞凋亡.表达HBV X基因后As2O3诱导的HepG2细胞凋亡比和Caspas3活性下降,特异性shRNA抑制HBV X基因表达后则无此效应,但这种效应与细胞周期无关.     

JNK/SAPK信号转导系统在三氧化二砷诱导肝癌细胞凋亡中的作用

目的:探讨JNK/SAPK信号转导系统在三氧化二砷(As2O3)诱导人肝癌细胞株HepG2凋亡过程中的作用.方法:采用MTT法观察不同浓度的As2O3对人类肝癌细胞株HepG2细胞生长的抑制作用;以流式细胞术观察细胞的凋亡率及生长周期的变化;以Western blot法检测p-MEK4、JNK、P-JNK、Caspase-3及PARP蛋白在As2O3作用下及SP600125阻断JNK信号转导通路情况下的表达.结果:各浓度As2O3均能明显抑制肝癌细胞HepG,增殖,且具有剂量依赖性和时间依赖性;流式细胞术(FCM)分析显示,As2O3能够诱导肝癌细胞HepG2凋亡且具有时间依赖性,细胞滞留于G2/M期(0,24,48,72 h百分率分别为7.22%±1.50%,11.56%±0.73%,33.8%±1.62%,46.02%±0.11%):Western blotting结果显示,As2O3诱导肝癌细胞HepG2凋亡伴随着Caspase-3和PARP的活化;As2O3作用于HepG2细胞10 min后P-MEK4和P-JNK蛋白表达开始增加,20 min达到高峰,30 min开始减少,总JNK蛋白的含量无明显改变,MEK4和JNK的激活早于细胞凋亡;用SP600125预处理HepG2细胞株后,可以明显减少Caspase-3和PARP的活化.结论:As2O3可以体外通过诱导细胞凋亡抑制肝癌细胞株HepG2的增殖,细胞凋亡通过Caspase-3途径实现.JNK信号转导通路参与了As2O3诱导的HepG2凋亡反应,并位于Caspase-3的上游.     

cag致病岛的差异及不同激酶抑制剂对幽门螺杆菌诱导胃上皮细胞IL-8分泌的影响

目的：分析中国临床分离的幽门螺杆菌的cag致病岛的差异和不同激酶抑制剂对幽门螺杆菌诱导中国人胃上皮细胞IL-8分泌的影响。方法：在体外分别用中国临床分离的cagA^ cagE^ 、cagA^ cagE^ 、cagA^ cagE^ 、cagA^ cagE^ 的幽门螺杆菌与中国人胃上皮细胞MGC-803共培养,IL-8分泌用ELISA进行检测,比较蛋白激酶A、C、G和蛋白酪氨酸激酶的抑制剂对幽门螺杆菌诱导胃上皮细胞IL-8分泌的影响。结果：cagA^ cagE^ 幽门螺杆菌显增加了胃上皮细胞IL-8的分泌,cagA^ cagE^ 、cagA^ cagE^ 幽门螺杆菌作用次之,而cagA^ cagE^ 幽门螺杆菌不能增加胃上皮细胞IL-8的分泌。蛋白激酶A、C、G的抑制剂不能阻断幽门螺杆菌增加胃上皮细胞IL-8的分泌,而蛋白酪氨酸激酶的抑制剂阻断了幽门螺杆菌增加胃上皮细胞IL-8的分泌。结论：cagA^ cagE^ 幽门螺杆菌显增加了胃上皮细胞IL-8的分泌并且依赖于蛋白酪氨酸激酶的活性。     

Aspirin-Induced Apoptosis in Human Gastric Cancer Epithelial Cells: Relationship with Protein Kinase C Signaling

This study examined the relationship of protein kinase C (PKC) signaling with apoptosis induced by aspirin (ASA) in gastric surface cancer cells (AGS cell line). We found increased expression of two PKC isoforms (α and β_II) that translocated from the cytosol into the cell membrane fraction after ASA (40 mM) stimulation. PKC β_I expression markedly decreased in response to ASA treatment. This process was independent of caspase activation because no caspase inhibitors used (i.e., inhibitors to caspase 3, 6, 7, 8, and total caspase activity) significantly changed PKC processing, although inhibition of caspase cascade activity markedly attenuated the apoptosis induced by ASA as measured by DNA-histone complex formation. Upstream PKC signaling induced by ASA seems to play an important role in the regulation of apoptosis because PKC inhibitors significantly reduced the magnitude of DNA-histone complex formation. We conclude that ASA-induced apoptosis in gastric cancer cells is mediated, at least in part, through a PKC mechanism involving the (α) and (β) isoforms and that PKC signaling operates upstream of the caspase cascade, which when activated elicits its downstream effects on DNA degradation.     

Monocytic activation of protein tyrosine kinase,protein kinase A and protein kinase C induced by porins isolated from Salmonella enterica serovar Typhimurium

OBJECTIVES: In the present study a monocytic cell line, U937, was used to investigate the possible involvement of protein tyrosine kinases (NT-PTKs), protein kinase A (PKA) and protein kinase C (PKC) in cell signaling pathways following Salmonella enterica serovar Typhimurium porin stimulation. METHODS: Different concentrations of porins and lipopolysaccharide (LPS) were analysed to evaluate changes in PTK activity by a non radioactive tyrosine kinase assay and in PKA and PKC phosphorylation by Western blotting analysis. The inhibitors of PTK, PKA and PKC activation used, were: 3,4-dihydroxybenzylidene-malononitrile (tyrphostin 23), inhibitor of epidermal growth factor (EGF) receptor tyrosine kinase activity; dihychloride (H-89), a selective inhibitor of PKA which is useful to discriminate between the effects of PKC and PKA; diacylglycerol kinase inhibitor II (R59949), which is useful for elucidating roles of PKC; calphostin C, a specific inhibitor of PKC. RESULTS: Porins of the outer membrane of the ST were isolated to be used as a stimulus in the performed experiments. Following porin treatment, a dose-dependent increase in PTK, PKA and PKC activation was observed. U937 monocytes pretreated with inhibitors induced an evident decrease in PTK activity and PKA and PKC phosphorylation pattern in porin stimulated monocytes. CONCLUSIONS: Our data support the important role played by NT-PTK, PKA and PKC in transducing the activating signal in macrophages stimulated with porins through the activation of the mitogen-activated protein kinase (MAPK) pathway that participate in the regulation of gene expression.     

Individual dose and scheduling determine the efficacy of combining cytotoxic anticancer agents with a kinase inhibitor in non-small-cell lung cancer

Purpose

To investigate the combination of conventional cytotoxic anticancer agents and a small molecule kinase inhibitor in preclinical models of non-small-cell lung cancer (NSCLC).

Methods

We compared the induction of apoptosis by DNA-damaging anticancer drugs and PKC412, a predominantly protein kinase C (PKC)-specific small molecule inhibitor, in six NSCLC cell lines of different histologic and genetic backgrounds. The outcome of various combinations and schedules of DNA-damaging agents and PKC412 was studied, and isobolograms were calculated. Conditional expression of pro-apoptotic BAK was applied to specifically target apoptotic signal transduction in combination with drug therapy.

Results

Resistance of NSCLC cells to DNA damage–induced apoptosis was mainly determined at the mitochondrial step of the intrinsic pathway of caspase activation. PKC412 effectively inhibited the growth factor signal transduction, but failed to induce apoptosis in NSCLC cells resistant to DNA-damaging agents. Combining conventional anticancer drugs with PKC412 at different doses and schedules resulted in unpredictable outcomes, including synergistic, additive, and antagonistic interactions. In contrast, conditional expression of BAK reliably sensitized drug-resistant NSCLC cells to apoptosis induced by cytotoxic agents or PKC412.

Conclusions

Combining DNA-damaging anticancer drugs with a pharmacologic inhibitor of growth and survival factor signaling in NSCLC may result in unpredictable treatment outcomes. In contrast, targeting specific death effector mechanisms, such as apoptotic signal transduction, is a promising strategy to sensitize NSCLC to cytotoxic agents or kinase inhibitors.     

氧化砷诱导胃癌细胞凋亡的实验研究

目的 研究三氧二化砷（氧化砷）对胃癌细胞的诱导凋亡作用。方法 应用ＴＵＮＥＬ染色、流式细胞仪技术研究氧化砷对胃癌细胞ＭＫＮ－４５、ＭＫＮ－２８的诱导凋亡作用。结果 氧化砷作用于不同分化程度的胃癌细胞后,可看到较为典型的细胞凋亡的形态学变化：细胞核固缩,染色质凝集,呈新月型紧贴于核膜周边,核碎裂,染色质片断化,凋 亡小体形成等。流式细胞仪ＤＮＡ直方图上出现典型的亚二倍体的“凋亡峰”。ＴＵＮＥＬ染色法     

Arsenic trioxide induces apoptosis in pancreatic cancer cells via changes in cell cycle,caspase activation,and GADD expression

We have previously shown that arsenic trioxide blocks proliferation and induces apoptosis in human pancreatic cancer cells at low, non-toxic concentrations. The mechanisms of the apoptosis was investigated in MiaPaCa2 and PANC-1 cells that have been previously shown to be responsive to arsenic trioxide. The results show the caspase-3, caspase-7, and caspase-9 are all activated by arsenic trioxide, together with cleavage of the downstream caspase-3 target poly ADP ribose polymerase (PARP). Expression of the anti-apoptosis proteins, Bcl-2 and Mcl-1 expression decreased time-dependently while Bax expression increased. These findings indicate that the Bcl family of proteins, the mitochondrial pathway and activation of the caspase cascade are responsible for arsenic-induced apoptosis. Flow cytometric analysis revealed changes of cell cycle distribution from a G0/G1 phase arrest at 24 hours to G2/M phase arrest at 72 hours following arsenic treatment. The sub-G0/G1 cell population of apoptotic cells was increased at these times. Arsenic increased expression of the P21 protein and decreased levels of cyclin A, cyclin B1 and cyclin D1, but expression of CDK2, CDK4, CDK6, and cyclin E were not affected. Arsenic trioxide markedly enhanced the expression of GADD45 and GADD153 in a time-dependent manner. In summary, arsenic trioxide induced apoptosis in pancreatic cancer cells through activating the caspase cascade via the mitochondrial pathway, GADD expression and by modifying cell cycle progress and changes in several cycle-regulating proteins. This old drug may be valuable for treatment of pancreatic cancer.     

Pharmacological Inhibition of Protein Kinase C Activity Could Induce Apoptosis in Gastric Cancer Cells by Differential Regulation of Apoptosis-Related Genes

The protein kinase C (PKC) signaling pathwayplays a key role in tumor cell proliferation,differentiation, and apoptosis. Gastric cancer usuallypossesses a higher level of PKC activity than normaltissue. We evaluated inhibition of PKC activity inapoptosis induction of gastric cancer cells and theexpression profile of apoptosis-related genes. Gastriccancer cells (AGS) were incubated with two highlyspecific PKC inhibitors (RO-31-8220 and chelerythrine).Cell viability and cell cycle were determined bymethyl-tetrazolium (MTT) assay and flow cytometry,respectively. Apoptosis was characterized by acridineorange staining, DNA gel electrophoresis, and flowcytometry. The expression of p53,p21^waf/cip1, c-myc, bcl-2, and bax wasdetermined by western blot. The results showed that bothPKC inhibitors hindered cell growth, arrested cells atG₀/G₁ phase and induced apoptosis.The protein level of p53, p21^waf/cip1, c-myc,and bax was elevated while bcl-2 kept unchangedfollowing drug exposure. In conclusion, PKC inhibitorssuppress growth of gastric cancer cells throughapoptosis induction and cell cycle quiescence, which maybe regulated by differential expression ofapoptosis-related genes.     

Inhibition of NF-kappaB essentially contributes to arsenic-induced apoptosis

Arsenic can induce apoptosis and is an efficient drug for the treatment of acute promyelocytic leukemia. Currently, clinical studies are investigating arsenic as a therapeutic agent for a variety of malignancies. In this study, Hodgkin/Reed-Sternberg (HRS) cell lines served as model systems to characterize the role of nuclear factor-kappaB (NF-kappaB) in arsenic-induced apoptosis. Arsenic rapidly down-regulated constitutive IkappaB kinase (IKK) as well as NF-kappaB activity and induced apoptosis in HRS cell lines containing functional IkappaB proteins. In these cell lines, apoptosis was blocked by inhibition of caspase-8 and caspase-3-like activity. Furthermore, arsenic treatment down-regulated NF-kappaB target genes, including tumor necrosis factor-alphareceptor-associated factor 1 (TRAF1), c-IAP2, interleukin-13 (IL-13), and CCR7. In contrast, cell lines with mutated, functionally inactive IkappaB proteins or with a weak constitutive IKK/NF-kappaB activity showed no alteration of the NF-kappaB activity and were resistant to arsenic-induced apoptosis. A direct role of the NF-kappaB pathway in arsenic-induced apoptosis is shown by transient overexpression of NF-kappaB-p65 in L540Cy HRS cells, which protected the cells from arsenic-induced apoptosis. In addition, treatment of NOD/SCID mice with arsenic trioxide induced a dramatic reduction of xenotransplanted L540Cy Hodgkin tumors concomitant with NF-kappaB inhibition. We conclude that inhibition of NF-kappaB contributes to arsenic-induced apoptosis. Furthermore, pharmacologic inhibition of the IKK/NF-kappaB activity might be a powerful treatment option for Hodgkin lymphoma.     

Inhibition of Akt/PKB by a COX-2 inhibitor induces apoptosis in gastric cancer cells

BACKGROUND/AIM: Inhibition of cyclooxygenase-2 has been proposed to be a potential mechanism for the chemoprevention of gastrointestinal tumors by nonsteroidal anti-inflammatory drugs. This study investigates the mechanisms by which the cyclooxygenase-2 inhibitor SC236 induces apoptosis of gastric cancer cell lines and its downstream signaling pathway. METHODS: Two gastric cancer cell lines, AGS and MKN28, were treated with SC236 and assessed for cell growth and apoptosis. The involvement of mitogen-activated protein kinase and Akt kinase/protein kinase B (Akt/PKB) pathways and their downstream signalings were studied in the AGS cell line. RESULTS: SC236 treatment induced apoptosis in gastric cancer cells and caused activation of p38 and stress-activated protein kinase/jun kinase, but down-regulated Akt/PKB. The specific p38 inhibitor SB203580 and the dominant-negative stress-activated protein kinase/jun kinase both failed, while the constitutively active form of Akt/PKB was able to block SC236-induced apoptosis. SC236-induced apoptosis was coupled with release of cytochrome c and activation of caspases. CONCLUSION: One of the pathways involved in SC-236-induced apoptosis in gastric cancer cells is through downregulation of Akt and then release of cytochrome c.