Water Extract of Rice False Smut Balls Activates Nrf2/HO-1 and Apoptosis Pathways,Causing Liver Injury

Ustiloxins are vital cyclopeptide mycotoxins originally isolated from rice false smut balls that form in rice spikelets infected by the fungal pathogen Ustilaginoidea virens.The toxicity of the water extract of rice false smut balls(RBWE) remains to be investigated.Studies have shown that RBWE may be toxic to animals,but toxicological evidence is still lacking.In this study,we found that the IC50 values of RBWE to BNL CL.2 cells at 24 and 48 h were 40.02 and 30.11 μg/m L,respectively,with positive correlations with dose toxicity and time toxicity.After treatment with RBWE,the number of BNL CL.2 cells decreased significantly,and the morphology of BNL CL.2 cells showed atrophy and wall detachment.RBWE induced DNA presynthesis phase arrest of BNL CL.2 cells,increased the proportion of apoptotic cells and inhibited cell proliferation.RBWE up-regulated reactive oxygen species(ROS) levels and lowered mitochondrial membrane potentials.Additionally,Western blot and q RT-PCR results suggested that RBWE exerted the above effects by promoting the Nrf2/HO-1 and caspase-induced apoptosis pathways in vitro and in vivo.The contents of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and total bile acids in the serum of mice from Institute of Cancer were significantly up-regulated by RBWE.At the same time,RBWE can lead to increases in ROS and malondialdehyde contents,decreases in contents of oxidized glutathione,glutathione and reduced glutathione,as well as decrease in catalase and superoxide dismutase activities in mouse liver tissues,demonstrating that oxidative stress occurred in mice.Moreover,liver damage was further detected by haematoxylin-eosin staining and electron microscopy to verify the damage to the mice caused by RBWE.In general,RBWE may cause hepatotoxicity in vivo and in vitro via the apoptosis pathway,which provides a reference for hepatotoxicity and its mechanism of action.

Environmental hypoxia induces apoptosis in large yellow croaker Larimichthys crocea via both intrinsic and extrinsic pathways

Hypoxia has become an unfavorable factor affecting the sustainable development of the large yellow croaker Larimichthys crocea,an economically important mariculture fish in China.Apoptosis is a consequence of hypoxia on fish.However,the effects of hypoxia stress on apoptosis in L.crocea remain largely unknown.We investigated the effect of environmental hypoxia on apoptosis in L.crocea.Results show that hypoxia induced apoptosis in L.crocea both in vivo and in vitro.The mitochondrial membrane potential was significantly reduced in large yellow croaker fry(LYCF)cells.The expression levels of Bcell lymphoma/leukemia-2(Bcl-2)m RNA and protein were also significantly decreased in the liver and LYCF cells during 96 h and 48 h of hypoxia stress,respectively,whereas the expression level of Bcl-2 associated X(Bax)mRNA,Casp3 mRNA,and activity of caspase-3/7/9 were significantly increased,indicating that hypoxia induced caspase-dependent intrinsic apoptosis in L.crocea.The expression level of the apoptosis-inducing factor(AIF)protein was significantly increased in the liver and LYCF cells.The level of AIF protein was significantly decreased in the cytoplasm but increased in the nuclei of L.crocea,demonstrating that hypoxia induced the AIF-mediated caspase-independent intrinsic apoptosis.In addition,the activity of caspase-8 was significantly increased,indicating that hypoxia stress induced extrinsic apoptosis in L.crocea.Therefore,hypoxia induced apoptosis in L.crocea through both the intrinsic and extrinsic pathways.The present study accumulated basic biological information to help elucidate the mechanism of hypoxia response in marine fish.

Apoptosis of colon cancer CT-26 cells induced polysaccharide from Cyclocarya paliurus and its phosphorylated derivative via intrinsic mitochondrial passway

In this study,the antitumor properties and the possible molecular mechanisms of Cyclocarya paliurus polysaccharide(CP)and its phosphorylated derivative(P-CP)on CT-26 mouse colon carcinoma cells were investigated.Results found that CP had high inhibition ratio against CT-26 cells.The flow cytometry results found that CP treatment could cause the intracellular acidification,arrest the cell cycle in the S phase and increase reactive oxygen species generation.Additionally,CP treatment triggered mitochondrial membrane potential depolarization and Ca^(2+)overloading,and broke down the balance of antioxidant system,Na^(+)/K^(+)-ATPase and Ca^(2+)-ATPase.Further analysis found CP induced cell apoptosis through improving the activities of caspase-3 and caspase-9,and increasing the level of cytochrome C.Furthermore,the comparative study of antitumor effect on CT-26 cells displayed that the phosphorylation enhanced antitumor activities of polysaccharides.These results suggest CP is a potential natural therapeutic agent for colon cancer and phosphorylation represents an effective method of enhancing the antitumor activity of CP.

Effects of Low Concentrations of Di-(2-ethylhexyl) and Mono-(2-ethylhexyl) Phthalate on Steroidogenesis Pathways and Apoptosis in the Murine Leydig Tumor Cell Line MLTC-1

The aim of this study was to evaluate the effects of low concentrations of DEHP and MEHP on steroidogenesis in a murine Leydig tumor cell line （MLTC-1） in vitro. The result of flow cytometry analysis revealed that the proportion of apoptotic cells was significantly increased after the exposure to DEHP. All three genes （P450scc, P450c17, and 38HSD） under study showed an increased expression following exposure to DEHP or MEHP, although some insignificant inhibitory effects appeared in the 10μmol/L treatment group as compared with the controls. It was also found that DEHP or MEHP stimulated INSL3 mRNA and protein especially in the 0.001 μmol/L treatment group. Testosterone secretions were stimulated after the exposure to DEHP or MEHP. Alterations of steroidogenic enzymes and INSL3 in MLTC-1 cells might be involved in the biphasic effects of DEHP/MEHP on androgen production.

Essential Oil from Siegesbeckia pubescens Induces Apoptosis through the Mitochondrial Pathway in Human HepG2 Cells

Siegesbeckia pubescens（SP） has been used as a traditional medicine for the treatment of and inflammatory diseases. However, the activities of SP against hepatocellular carcinoma and the related mechanisms remain unclear. The present study aimed to examine the effects of the essential oil of SP（SPEO） on the proliferation of hepatocellular carcinoma cells and the possible mechanisms. The growth inhibition of Hep G2 cells was analyzed by MTT assay. Hoechst 33258 and fluorescence microscopy were utilized to observe the nuclear morphological changes of apoptotic cells. Flow cytometry was used to detect cell apoptosis and cell cycle. The expressions of the target proteins were detected by Western blotting. The results showed that SPEO obviously inhibited the proliferation of Hep G2 cells in a dose-dependent manner. SPEO activated a series of apoptotic proteins in Hep G2 cells, increasing expression levels of Bax, caspase-3 and caspase-9, and decreasing the bcl-2 expression level. SPEO displayed promising anti-hepatocellular carcinoma activities in vitro, partly by inducing apoptosis in Hep G2 cells through activating the mitochondrial pathway.

Panax notogiseng saponin inhibits ischemia-induced apoptosis by activating PI3K/Akt signal pathway in cardiomyocytes

The panax notoginseng saponin(PNS) had been clinically used for the treatment of cardiovascular diseases and stroke in China.It had been demonstrated that PNS could protect cardiomyocytes from injury induced by ischemi- a,but the underlying molecular mechanisms of this protective effect were still unclear.This study was aimed to investigate the protective effect and molecular mechanisms of PNS on apoptosis in H9c2 cells in vitro and rat myocardial ischemia injury model in vivo.Annexin-V/PI assay shew that PNS could protect H9c2 cells from apoptosis induced by serum, glucose and oxygen deprivation(SGOD) in a dose-dependent manner.However,the anti-apoptotic effect of PNS was reversed by LY294002,a specific PI3K inhibitor.This antiapoptotic effect of PNS was confirmed by JC-1,a specific probe of mitochondrial membrane potential staining.PNS could significantly increase phos-Akt in H9c2 cells by Western blot assays and its effect could be inhibited by LY294002.Furthermore,PNS could improve ischemic-induced left ventricular function as reflected by EF,LVDd and LVDs.PNS could also inhibited cellular apoptosis in myocardial tissues in ischemic rats by TUNEL assay.PNS administration also increased the expression of phos-Akt in rat ischemic myocardial tissues.These results suggested that PNS could protect myocardial cells from apoptosis induced by ischemia in vitro model and in vivo model through activating-PI3K/Akt signal pathway which may be meaningful for further understanding the molecular mechanisms of cardiac protection of PNS.And the results might be useful in treatment of myocardial ischemia in future.

Anti-proliferation and apoptosis-inducing effects of sodium aescinate on retinoblastoma Y79 cells

AIM:To investigate the anti-proliferation and apoptosisinducing effects of sodium aescinate(SA)on retinoblastoma Y79 cells and its mechanism.METHODS:Y79 cells were cultured at different drug concentrations for different periods of time(24,48,and 72 h).The inhibitory effect of SA on proliferation of Y79 cells was detected by the cell counting kit-8(CCK-8)assay,and the morphology of Y79 cells in each group was observed under an inverted microscope.An IC50 of 48 h was selected for subsequent experiments.After pretreatment with SA for 24 and 48 h,cellular DNA distribution and apoptosis were detected by flow cytometry.Real-time qunatitative polymerase chain reaction(RT-qPCR)and Western blot were used to assess changes in related genes(CDK1,CyclinB1,Bax,Bcl-2,caspase-9,caspase-8,and caspase-3).RESULTS:SA inhibited proliferation and induced apoptosis of Y79 cells in a time-dependent and concentrationdependent manner.Following its intervention in the cell cycle pathway,SA can inhibit the expression of CDK1 and Cyclin B1 at the mRNA and protein levels,and block cells in the G2/M phase.In caspase-related apoptotic pathways,up-regulation of Bax and down-regulation of Bcl-2 caused caspase-9 to self-cleave and further activate caspase-3.What’s more,the caspase-8-mediated extrinsic apoptosis pathway was activated,and the activated caspase-8 was released into the cytoplasm to activate caspase-3,which as a member of the downstream apoptotic effect group,initiates a caspase-cascade reaction that induces cell apoptosis.CONCLUSION:SA inhibits the proliferation of Y79 cells by arresting the cell cycle at the G2/M phase,and induces apoptosis via the caspase-related apoptosis pathway,indicating that SA may have promising potential as a chemotherapeutic drug.

Dioscin-induced Apoptosis of Human LNCaP Prostate Carcinoma Cells through Activation of Caspase-3 and Modulation of Bcl-2 Protein Family

Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin against human LNCaP cells, and evaluated the possible mechanism involved in its antineoplastic action. It was found that dioscin（1, 2 and 4 μmol/L） could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer. Western blotting was employed to detect the expression of caspase-3, Bcl-2 and Bax in LNCaP cells. The expression of cleaved caspase-3 was significantly increased, and meanwhile procaspase-3 was markedly decreased. The expression of anti-apoptotic protein Bcl-2 was down-regulated, whereas the pro-apoptotic protein Bax was up-regulated. Moreover, the Bcl-2/Bax ratio was drastically decreased. These results suggested that dioscin possessed potential anti-tumor activity in human LNCaP cells through the apoptosis pathway, which might be associated with caspase-3 and Bcl-2 protein family.

Dynamic Imaging of Autophagy-lysosomal Pathway and Autophagy Function Following Pulmonary Hypoxia/Reoxygenation In Vitro

Alterations of the autophagy-lysosomal pathway（ALP） and autophagy have been involved in lung ischemia-reperfusion（I/R） injury. However, dynamic imaging of ALP function under lung I/R injury particularly is not fully understood. Here we depicted the live-cell fluorescence imaging of autophagosome to monitor ALP activation and autophagy function. The p As Red2-N1-LC3 vectors were transfected into CRL-2192 NR8383（an alveolar macrophage cell line） and CCL149（an alveolar epithelial cell line） successfully. 0-h, 2-h, 4-h, and 6-h hypoxia/0-h, 2-h, 4-h, and 6-h reoxygenation were then induced with an ALP inhibitor（3-MA） or activator（rapamycin） in the culture of transfected cells separately. ALP activation was conformed by up-regulating AMPK and beclin1 expression. Apoptosis was not obvious in 2-h hypoxia/2-h reoxygenation. p As Red2-N1-LC3 CCL149 and p As Red2-N1-LC3 NR8383 cells revealed gradually enhanced As Red2 from 2-h to 6-h hypoxia/reoxygenation. As Red2 varied sensitively to 3-MA and rapamycin interventions during 2-h hypoxia/reoxygenation. Our data provides a simple method of autophagosome imaging to monitor ALP activation and autophagy function in lung I/R injury.

Baicalin protects neonatal rat brains against hypoxicischemic injury by upregulating glutamate transporter 1 via the phosphoinositide 3-kinase/protein kinase B signaling pathway

Baicalin is a flavonoid compound extracted from Scutellaria baicalensis root.Recent evidence indicates that baicalin is neuroprotective in models of ischemic stroke.Here,we investigate the neuroprotective effect of baicalin in a neonatal rat model of hypoxic-ischemic encephalopathy.Seven-day-old pups underwent left common carotid artery ligation followed by hypoxia（8% oxygen at 37°C） for 2 hours,before being injected with baicalin（120 mg/kg intraperitoneally） and examined 24 hours later.Baicalin effectively reduced cerebral infarct volume and neuronal loss,inhibited apoptosis,and upregulated the expression of p-Akt and glutamate transporter 1.Intracerebroventricular injection of the phosphoinositide 3-kinase/protein kinase B（PI3 K/Akt） inhibitor LY294002 30 minutes before injury blocked the effect of baicalin on p-Akt and glutamate transporter 1,and weakened the associated neuroprotective effect.Our findings provide the first evidence,to our knowledge that baicalin can protect neonatal rat brains against hypoxic-ischemic injury by upregulating glutamate transporter 1 via the PI3 K/Akt signaling pathway.

HSP70 inhibitor combined with cisplatin suppresses the cervical cancer proliferation in vitro and transplanted tumor growth:An experimental study

Objective:To study the regulating effect of HSP70 inhibitor(PES) combined with cisplatin on cervical cancer proliferation in vitro and transplanted tumor growth.Methods:Cervical cancer Hela cell lines were cultured and divided into control group,cisplatin group,PES group and cisplatin+PES group that were treated with serum-free DMEM,cisplatin with final concentration of 10 μmol/L,PES 20 μmol/L and cisplatin 10 μmol/L combined with PES with 20 μmol/L,respectively;animal models with cervical cancer xenografts were established and divided into control group,cisplatin group,PES group and cisplatin+PES group who received intra-tumor injection of normal saline,10 μmol/L cisplatin,20 μmol/L PES as well as 10 μmol/L cisplatin+20 μmol/L PES,respectively.Cell proliferation activity,transplanted tumor volume and mitochondria apoptosis molecule expression were detected.Results:Cell viability value and Bcl-2 mRNA expression in cells of cisplatin group,PES group and cisplatin+PES group were significantly lower than those of control group while Bax,Caspase-3 and Caspase-9 mRNA expression in cells were significantly higher than those of control group;transplanted tumor volume and the Bcl-2 mRNA expression in transplanted tumor tissue of cisplatin group,PES group and cisplatin+PES group were significantly lower than those of control group while Bax,Caspase-3 and Caspase-9 m RNA expression in transplanted tumor tissue were significantly higher than those of control group.Conclusions:HSP70 inhibitor combined with cislatin can inhibit cervical cancer cell proliferation in vitro and transplanted tumor growth through mitochondrial apoptosis pathway.

Real-time in situ observation of P53-mediated cascade activation of apoptotic pathways with nucleic acid multicolor fluorescent probes based on symmetrical gold nanostars

T-2 toxin,one of the most dangerous natural pollutants,induces apoptosis through multiple pathways.Amongst,P53 mediated apoptosis pathway,an important collection of molecules,plays a key role in cell vital activity.Real-time monitoring of upstream and downstream activation relationships of P53 mRNA,Bax mRNA,and cytochrome c(Cyt c)in signaling pathways is of great significance for understanding the apoptotic machinery in human physiology.In this work,a novel nucleic acid multicolor fluorescent probe,based on silica-coated symmetric gold nanostars(S-AuNSs@SiO_(2)),was developed for highly sensitive in situ real-time imaging of P53 mRNA,Bax mRNA,and Cyt c during T-2 toxin-induced apoptosis.The nucleic acid chains modified with carboxyl groups were modified on the surface of S-AuNSs@SiO_(2)by amide reaction.The complementary chains of targeted mRNA and the aptamer of targeted Cyt c were modified with different fluorophores,respectively,and successfully hybridized on S-AuNSs@SiO_(2)surface.When targets were present,the fluorescent chains bound to the targets and detached from the material,resulting in the quenched fluorescence being revived.The probes based on S-AuNSs showed excellent performance is partly ascribed to the presence of 20 symmetric“hot spots”.Notably,the amide-bonded probe exhibited excellent anti-interference capability against biological agents(nucleases and biothiols).During the real-time fluorescence imaging of T-2 toxin-induced apoptosis,the corresponding fluorescence signals of P53 mRNA,Bax mRNA,and Cyt c were observed sequentially.Therefore,S-AuNSs@SiO_(2)probe not only provides a novel tool for real-time monitoring of apoptosis pathways cascade but also has considerable potential in disease diagnosis and pharmaceutical medical.

Viscum Album Modulates Apoptotic Related Genes in Melanoma Tumor of Mice

Cancer is a major public health problem throughout the world. It is estimated that one third of the American population will develop the disease at some time during their lifetimes. Among these, melanoma will account for 7% of the cases. In Brazil, in 2012, it is estimated that over six thousand new melanoma cases occurred. During recent years, the incidence of melanoma has increased, mainly due to a more constant exposure of the skin to sunlight. In this work, our aim is to assess the expression of apoptotis-related genes melanoma tumors in mice treated with Viscum album (VA). This will allow us to better understand the molecular mechanisms underlying tumor cell death activation caused by this compound. Our results clearly demonstrate upregulation of pro apoptotic genes (Trp53bp2, Nol3, Fadd, Tnfsf10, Traf1, Traf2, Cflar, Card10, Nod1, Casp 2, Casp7, Xiap, Dad1, and Dffb). Further bioinformatics-based tool analysis allowed us to assess which specific cell death-related intracellular pathways were activated by VA treatment. Two major effects of VA in melanoma cells could be observed: generation of an immunomudulatory Th-1 like action, recruiting several interleukines, and cell death activation through Caspase7, associated uspstream with Card10 and downstream with CAD. In summary, VA modulates apoptosis related genes in cancer melanoma cells. Although a deeper study should be conducted, VA seems to interfere with important signaling pathways within melanoma cells that control the cellular mechanisms of apoptosis activation. Therapeutic approaches using VA as an antineoplastic and adjuvant medication compounding should be considered.

Neuroprotective effect of the Chinese medicine Tiantai No.1 and its molecular mechanism in the senescence-accelerated mouse prone 8

Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2：1：2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No.1 intragastrically to senescence-accelerated mouse prone 8（SAMP8） mice（a model of Alzheimer＇s disease） at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer＇s disease-related proteins in the brain. Tiantai No.1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No.1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No.1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No.1 is neuroprotective in the SAMP8 mouse model of Alzheimer＇s disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.

Combination of Total Astragalus Extract and Total Panax Notoginseng Saponins Strengthened the Protective Effects on Brain Damage through Improving Energy Metabolism and Inhibiting Apoptosis after Cerebral Ischemia-Reperfusion in Mice

Objective： To explore the effects and molecular mechanisms of the combination between total Astragalus extract （TAE） and total Panax notoginseng saponins （TPNS） against cerebral ischemia- reperfusion injury. Methods： C57BL/6 mice were randomly divided into sham-operated group, model group, TAE （110 mg/kg） group, TPNS （115 mg/kg） group, TAE-TPNS combination group and Edaravone （4 mg/kg） group, treated for 4 days, then, cerebral ischemia-repeffusion injury was established by bilateral common carotid artery （CCA） ligation for 20 min followed by reperfusion for 1 and 24 h. Results： TPNS could increase adenosine triphosphate （ATP） level, TAE and TAE-TPNS combination increased ATP, adenosine diphosphate （ADP） contents and Na＋-K＋-ATPase activity, and the effects of TAE-TPNS combination were stronger than those of TAE or TPNS alone after reperfusion for 1 h. After reperfusion for 24 h, TAE, TPNS and TAE-TPNS combination significantly increased neurocyte survival rate and decreased the apoptosis rate as well as down-regulated the expression of phosphorylated c-June N-terminal kinasel/2 （p-JNK1/2）, cytochrome C （Cyt C）, cysteine aspartic acid-specific protease （Caspase）-9 and Caspase-3. Furthermore, the effects in TAE-TPNS combination were better than those in TAE or TPNS alone. Conclusion： The combination of TAE 110 mg/kg and TPNS 115 mg/kg could strengthen protective effects on cerebral ischemia injury, the mechanism underlying might be related to improving jointly the early energy metabolism, and relieving the delayed apoptosis via inhibiting the mitochondrial apoptosis pathway of JNK signal transduction.

Xuezhikang(血脂康) Reduced Renal Cell Apoptosis in Streptozocin-Induced Diabetic Rats through Regulation of Bcl-2 Family

Objective： To investigate the effect of Xuezhikang（血脂康, XZK） on renal cell apoptosis in diabetic rats and the possible mechanism. Methods： Sixty-six rats were randomly divided into 3 groups： the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK（1200 mg/kg body weight） everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours＇ urine was collected for urinary albumin excretion（UAE） measurement. Periodic acid-Schiff（PAS） and Masson＇s trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by Td T-mediated d UTP nick end labeling（TUNEL） staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C（Cyt C） and caspase-9 concentration were detected by Western blot. Results： Compared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months（P〈0.05 or P〈0.01）. Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson＇s trichromestained collagen to different extent. Conclusions： Renal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.

Apoptotic Signal Pathways and Regulatory Mechanisms of Cancer Cells Induced by IL-24

The melanoma differentiation-associated gene-7（mda-7）,IL-24,has the specific functions that induce cancer cell apoptosis without doing harm to normal cells. We systematically review the apoptotic signal pathways and their regulatory mechanisms induced by Ad.IL-24 and IL-24 in diverse cancer cells. IL-24 can participate in varied signal transduction pathways,including JAK,p38 MAPK,Wnt/β-catenin,JNK,ER stress and mitochondria-associated signal pathways. And we review five proteins interacting with IL-24,including Bip/GRP78,S1 R,PKR,Beclin1 and soluble clusterin,which are relative to the tumor-specific effect of IL-24. It is speculated that ER stress,G-protein pathways and MAPK signal pathways may be the primary upstream effectors which activate the sequential downstream mediators resulting in apoptosis induced by IL-24 in tumor cells. Experimental results also show that IL-24 sensitizes cancer cells and indirectly promotes apoptosis rather than functions as a direct apoptosis inducer itself.