INTRODUCTION:Prolyl 4-hydroxylase beta peptide (P4HB) is a novel diagnostic and prognostic marker associated with cancer progression and clinical outcomes, and it is upregulated in multiple types of cancer cells. However, the influence and potential mechanisms of P4HB on the migration, invasion, and epithelial-mesenchymal transition (EMT) of bladder cancer cells remain unclear. This study aims to clarify the role of P4HB in the migration, invasion, and EMT of bladder cancer cells and to explore its potential mechanism related to the Claudin-1/AMPK/TGF-β1 pathway. METHODS:The mRNA and protein expression levels of P4HB were examined in human ureteral epithelial cells (SV-HUC-1) and five bladder cancer cell lines (J82, T24, 5637, UM-UC-3, and RT4). Stable cell lines with P4HB overexpression and knockdown were constructed, and the effects of P4HB on migration, invasion, EMT, and the expression of EMT-related genes in bladder cancer cells were analyzed using wound healing assays, Transwell invasion assays, cellular morphology observations, real-time quantitative PCR, in-cell western blotting, western blotting, and enzymelinked immunosorbent assays. Furthermore, Claudin-1 siRNA was transfected into P4HBoverexpressing cells to investigate its potential role in P4HB-induced invasion and EMT in bladder cancer cells. RESULTS:P4HB mRNA and protein expressions were significantly upregulated in human bladder cancer cell lines compared to those in ureteral epithelial cells. Cell migration, invasion, and EMT were significantly promoted in P4HB-overexpressing stable bladder cancer cells and suppressed in P4HB-knockdown cells. Furthermore, interference with P4HB downregulated EMT-related Claudin-1 mRNA and protein expressions and regulated the expression of downstream genes and proteins of Claudin-1. Moreover, interference of Claudin-1 with its siRNA significantly reversed the invasion and EMT induced by P4HB-overexpression, however, the effect of Claudin-1 siRNA was revised by TGF-β1 agonist and AMPK inhibitor. CONCLUSION:P4HB promoted migration, invasion, and EMT of bladder cancer cells by activating the Claudin-1/AMPK/TGF-β1-related pathway.

BACKGROUND:Aloperine (ALO) is a vital alkaloid present in the traditional Chinese herb Sophora alopecuroides, which has demonstrated effective anti-inflammatory activity. However, the effects and the mechanism of action of ALO on cisplatin (CDDP)-induced nephrotoxicity remain unclear. OBJECTIVE:This study aimed to investigate the effects of ALO on CDDP-induced nephrotoxicity and its potential mechanism of action in vitro. METHODS:Cell viability, lactate dehydrogenase cytotoxicity, apoptosis, activity of Caspase-Glo 3/7 and 1, in-cell western blotting, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA) were performed to assess the influence of ALO on CDDP-treated kidney cells. Inhibitors of phosphatidylinositol 3-kinase (PI3K, LY294002), protein kinase B (Akt, AKT inhibitor VIII), and nuclear factor kappa B (NFκB, BAY 11-7082) were used to determine their potential mechanisms of action. RESULTS:The results indicated that ALO significantly reversed the inhibition of cell viability, cytotoxicity, apoptosis, and the release of inflammatory factors induced by CDDP in kidney cells. ALO attenuated the PI3K/AKT/NFκB-mediated pathway activated by CDDP treatment and downregulated the CDDP-induced nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. Furthermore, the PI3K and AKT inhibitors diminished the effects of ALO on CDDP-treated kidney cells. Additionally, NFκB inhibitors reversed the effects of the PI3K and AKT inhibitors on ALO in CDDP-treated kidney cells. CONCLUSION:These results suggest that ALO protects against CDDP-induced injury in kidney cells by modulating the PI3K/AKT/NFκB-mediated NLRP3 inflammasome.

Isoflavones, a group of soybean nutrients, have been found to provide a wide range of benefits to the human body. The prospective cohort study aims to examine the association of dietary intake of isoflavones with all-cause mortality and heart disease mortality in the US. In this study, We conducted to explore the potential correlation of isoflavones (total isoflavones, genistein, and daidzein) intake with the risk of all-cause mortality and heart disease mortality. The mortality status and the heart disease cause of death were determined by NHANES-linked National Death Index public access files through December 31, 2019. The association of dietary isoflavones intake with all-cause mortality and heart disease mortality was analyzed by multivariate Cox regression model to compute hazard ratio (HR) and 95

BACKGROUND:Aloperine (ALO) is an important active ingredient in the traditional Chinese medicinal plant Sophora alopecuroides L and has a significant autophagy-stimulating effect. The effect of ALO on cytotoxicity caused by UVB radiation in skin fibroblasts and the potential mechanism remains unclear. OBJECTIVE:The present study aimed to assess the effect of ALO on UVB-induced damage in skin fibroblasts and investigate its possible mechanism. METHODS:Cell viability, cytotoxicity, caspase-Glo 3/7 activity, apoptosis, and protein expression were measured in UVB-treated skin fibroblasts in the presence or absence of ALO. Autophagy inhibitors (chloroquine and bafilomycin A1) and TFE3 siRNA transfection were used to elucidate the potential mechanisms further. RESULTS:These data demonstrate that ALO attenuated cell viability inhibition, apoptosis, cytotoxicity, and alterations in autophagy-related proteins caused by UVB exposure in skin fibroblasts. ALO stimulates autophagy activation and TFE3 nuclear localization in UVB-treated skin fibroblasts. Furthermore, treatment with autophagy inhibitors and TFE3 siRNA reversed the effects of ALO on UVB-treated skin fibroblasts. CONCLUSION:These results suggest that ALO protects skin fibroblasts against UVB-induced cytotoxicity by stimulating TFE3/Beclin-1-mediated autophagy.

Background Aloperine (ALO) is an important active component of quinolizidine alkaloids in Sophora flavescens A and Sophora alopecuroides L, and has effective anticancer activity against multiple cancers. However, the influence and mechanism of ALO on migration, invasion, and adhesion in bladder cancer cells remain unclear. Objective The aim of this study is to determine the anticancer effect of ALO on migration, invasion, and adhesion in bladder cancer cells and to investigate its potential TIMP-4-related mechanism. Methods Cell viability, cytotoxicity, wound healing, Transwell invasion, cell adhesion, real-time qPCR, western blot, and ELISA assays were performed to analyze the effect of ALO on migration, invasion, and adhesion in bladder cancer 5637 and UM-UC-3 cells. Furthermore, the anti-TIMP-4 antibody was used to explore the potential effect on ALO-inhibited bladder cancer cells. Results We have found that ALO significantly suppressed migration, invasion, and adhesion in bladder cancer cells. Furthermore, ALO could downregulate the expression of MMP-2 and MMP-9 mRNAs and proteins, and increase the expression of TIMP-4 mRNA and protein. Moreover, the anti-TIMP-4 antibody reversed the prevention of migration, invasion, and adhesion in ALO-treated bladder cancer cells. Conclusion The data in this study suggest that ALO suppressed migration, invasion, and adhesion in bladder cancer cells by upregulating the expression of TIMP-4.

Background MicroRNA-200c (miR-200c) is one of the short noncoding RNAs that play crucial roles in tumorigenesis and tumor progression. It also acts as considerable modulator in the process of epithelial-to-mesenchymal transition (EMT), a cell development regulating process that affects tumor development and metastasis. However, the role of miR-200c in bladder cancer cells and its mechanism has not been well studied. The purpose of this study was to determine the potential role of miR-200c in regulating EMT and how it contributed to bladder cancer cells in invasion, migration and proliferation. Methods Real-time reverse transcription-PCR was used to identify and validate the differential expression of MiR-200c involved in EMT in 4 bladder cancer cell lines and clinical specimens. A list of potential miR-200 direct targets was identified through the TargetScan database. The precursor of miR-200c was over-expressed in UMUC-3 and T24 cells using a lentivirus construct, respectively. Protein expression and signaling pathway modulation were validated through Western blot analysis and confocal microscopy, whereas BMI-1 and E2F3, direct target of miR-200c, were validated by using the wild-type and mutant 3’-untranslated region BMI-1/E2F3 luciferase reporters. Results We demonstrate that MiR-200c is down-regulated in bladder cancer specimens compared with adjacent ones in the same patient. Luciferase assays showed that the direct down-regulation of BMI-1 and E2F3 were miR-200c-dependent because mutations in the two putative miR-200c-binding sites have rescued the inhibitory effect. Over-expression of miR-200c in bladder cancer cells resulted in significantly decreased the capacities of cell invasion, migration and proliferation. miR-200c over-expression resulted in conspicuous down-regulation of BMI-1and E2F3 expression and in a concomitant increase in E-cadherin levels. Conclusions miR-200c appears to control the EMT process through BMI-1 in bladder cancer cells, and it inhibits their proliferation through down-regulating E2F3. The targets of miR-200c include BMI-1 and E2F3, which are a novel regulator of EMT and a regulator of proliferation, respectively.

Aloperine is a major active component in Sophora alopecuroides L that plays diverse pharmacological properties. Recent studies have indicated the potential effect of aloperine against hypertension and cancers. However, possible toxicity of aloperine has not been carefully studied in vivo. The aim of this study was to assess the effect of intraperitoneal aloperine injection on mouse liver and kidney tissues and to investigate the role of CYP450 genes in aloperine-induced toxicity. 72 BALB/c mice were randomly divided into four groups: vehicle control group (normal saline), low-dose group (4 mg/kg), medium-dose group (8 mg/kg), and high-dose group (16 mg/kg). 18 mice in each group were intraperitoneally injected with aloperine daily for 4 weeks, and were then kept for another 1 or 4 weeks without aloperine treatment. Serum was colleted for analysis of serum biochemical indexes including ALT, AST, BUN and CRE. The liver and kidney were collected for analysis of histopathologic changes and CYP450 expression and activity. Vacuolization of cytoplasm in liver cells, swelling in kidney tubular cells, increased levels of ALT, AST, BUN, and CRE, and alteration in the expression and activity of CYP450 were observed in the high-dose group after 4 weeks of treatment. However, all aloperine-induced damages were recovered to a certain degree after maintained without aloperine for 1 week, and fully recovered after maintained without aloperine for 4 weeks. These findings suggested that aloperine regulated the expression of CYP450, which was possibly involved in aloperine-induced reversible toxicity in mouse liver and kidney tissues.

Matrine is major active component in Sophora flavescens Ait that plays pharmacological activities against inflammation, tumors and virus. However, potential toxicity of matrine and its possible toxic mechanisms have not been carefully studied. The aim of the study is to assess the toxicity of matrine on mouse liver cells and to investigate the potential ROS-associated mechanisms. Mice were randomly divided into three groups: vehicle control (normal saline), low-dose (50 mg/kg), and high dose (100 mg/kg) groups. Mice in each group were intraperitoneally injected with matrine daily for 7 d. The livers were collected for analysis of histopathological changes and HO-1 protein expression. Serum was collected for analysis of aspartate aminotransferase and alanine aminotransferase activities. Mouse liver NCTC cells were treated with matrine for certain time, and cell viability, cytotoxicity, apoptosis, expression of proteins, activities of caspase-3 and caspase-9, and levels of ROS generation, mitochondrial membrane potential, and ATP were examined. Increased activities of AST and ALT in serum, and vacuolar degeneration of cytoplasm in liver tissues were observed after treatment. Suppression of cell viability, increase of cytotoxicity, induction of apoptosis, alteration in the expression of apoptotic-related proteins, and activation of caspase-3 and caspase-9 were shown in matrine-treated NCTC cells. Furthermore, matrine induced ROS generation, and suppressed mitochondrial membrane potential and ATP levels, however, the antioxidant N-acetylcysteine reversed matrine-induced hepatotoxicity and ROS generation. These findings suggested that matrine stimulated the generation of ROS, which was possibly involved in matrine-induced toxicity in mouse liver cells in vitro and in vivo.

对槐定碱进行急性与亚急性毒性研究,以评估其安全性,为临床合理用药提供理论依据.急性毒性试验采用腹腔注射,给小鼠注射不同浓度槐定碱测定LD50,计算95％可信限范围.亚急性毒性试验将小鼠80只随机分为4组,1个对照组和3个试验组,每组20只,雌雄各半.对照组腹腔注射生理盐水,试验组分别注射12、23、45 mg/kg槐定碱,连续注射30 d并恢复30 d.试验期间每天观察小鼠临床表现,每周称体重,试验30 d后采血检查小鼠血常规和生化指标,采集心、肝、脾、肺、肾和大脑等器官计算脏器指数,并进行病理组织学观察.恢复30 d后采血检查小鼠血常规和生化指标.结果显示,槐定碱经腹腔注射对小鼠急性毒性LD50为62.60 mg/kg,95％可信限为56.48 mg/kg～69.57 mg/kg;亚急性毒性试验,连续30 d染毒期间,试验组与对照组相比体重增重减缓、血液白细胞数和淋巴细胞数显著减少、血清肌酐含量和天门冬氨酸氨基转移酶活性显著升高,其他血常规和生化指标与对照组差异不显著.试验组心、肝、肾和大脑均表现明显病理损伤,呈现不同程度的炎细胞浸润和细胞坏死.停止染毒恢复30 d后,试验组小鼠血液学指标除白细胞外其他指标均恢复正常,血清生化指标恢复正常.结果表明,槐定碱具有一定毒性,但停止染毒30 d后肝、肾等实质器官损伤可得到恢复.

BACKGROUND:Ovarian cancer is the most lethal gynecologic malignancy worldwide with poor prognosis owing to chemotherapy resistance and cancer relapse. Hence, there is an urgent need to develop novel anticancer agents against ovarian cancer.OBJECTIVE:The aim of this research is to investigate the possible anticancer activity of aloperine, an active ingredient from a traditional Chinese medicine Sophora alopecuroides, and to explore the possible Reactive Oxygen Species (ROS)-related mechanism.METHODS:Cell viability, cytotoxicity, apoptosis, ROS generation, and oxidant stress indicators were analyzed.RESULTS:Our results demonstrated that aloperine significantly induced inhibition of cell viability, promoted cytotoxicity and mitochondrial-related apoptosis, and increased ROS generation in ovarian cancer cells. Furthermore, the antioxidant α-lipoic acid reversed apoptosis in aloperinetreated cells. In addition, we identified hydrogen peroxide as the main type of ROS, and the antioxidant catalase suppressed the apoptotic inducing effect of aloperine whereas hydrogen peroxide supplement exacerbated the effect of aloperine in ovarian cancer cells.CONCLUSION:Taken together, our results indicated that aloperine could exert anti-ovarian cancer cell activity through a reactive oxygen species activation mechanism and suggested aloperine as a potential agent against ovarian cancer.

Background: Diosmetin (DIOS) is the aglycone of the flavonoid glycoside, diosmin, derived naturally from the leaves of the legume, Olea europaea, and Acacia farnesiana. It has potent anticancer activity against multiple forms of cancers. However, the role of DIOS in renal carcinoma and its mechanism of action remain unclear. Objective: The purpose of this study is to investigate the effect of DIOS on cell viability and apoptosis in renal carcinoma cells and explore the possible mechanism of action. Methods: Cell viability, cytotoxicity, caspase activity, apoptosis, and expression of apoptotic related proteins were analyzed in renal carcinoma ACHN cells. Results: The results showed that DIOS inhibited the cell viability, and induced cytotoxicity and apoptosis in ACHN cells. Furthermore, DIOS increased expression of p53 mRNA and proteins, and downregulated phosphorylation of the phosphoinositide 3-kinase and protein B kinase (PI3K/AKT). In addition, it was observed that the anticancer effect of DIOS was significantly enhanced by the p53 activator, but inhibited by the p53 inhibitor. Conclusion: Our data suggested that DIOS induced apoptosis in renal carcinoma ACHN cells by reducing AKT phosphorylation through p53 upregulation.

苦豆子是一种耐盐碱植物,广泛分布于我国西北部干旱荒漠草地,特别是盐碱化草地,已经成为遏制草地退化的重要植物,其资源储量十分丰富.因此,将苦豆子作为可利用的植物资源,发挥其本身的价值进行资源化开发利用,显得尤为重要.近年来,国内外围绕苦豆子的生物学特性、化学成分、药理活性、杀虫活性、毒性作用以及苦豆子生物碱制剂研发等方面进行了广泛而深入的研究,对加快苦豆子资源化利用发挥了重要的推动作用.文章从苦豆子的资源分布、化学成分、毒理作用以及综合利用等方面进行综述,以期为苦豆子资源化利用及其产品开发提供理论依据.

The aim of the present study was to investigate the influence of the nitric oxide donor prodrug JS-K (C13H16N6O8) on Taxol-induced apoptosis in prostate cancer cells, and to investigate a potential reactive oxygen species (ROS)-associated mechanism. The effect of JS-K on the anticancer activity of Taxol was assessed in prostate cancer cells; cell viability, colony formation, apoptosis, ROS generation and expression levels of apoptosis-associated proteins were investigated. The function of ROS accumulation in the combined effects of JS-K and Taxol was determined using the antioxidant N-acetylcysteine (NAC) and the pro-oxidant oxidized glutathione (GSSG). The results of the present study demonstrated that JS-K was able to increase Taxol-induced suppression of prostate cancer cell proliferation, apoptosis, ROS accumulation and upregulation of apoptosis-associated proteins. Furthermore, NAC reversed the effect of JS-K on Taxol-induced apoptosis and conversely, the pro-oxidant GSSG exacerbated the effect of JS-K on Taxol-induced apoptosis in prostate cancer cells. In conclusion, JS-K enhances the chemosensitivity of prostate cancer cells to Taxol, via the upregulation of intracellular ROS.

ETHNOPHARMACOLOGICAL RELEVANCE:Sophora alopecuroides L., a traditional Chinese herb, has been widely used to treat numerous diseases throughout China. Quinolizidine alkaloids were identified as active components in Sophora alopecuroides L., and Sophoridine (SRI) is the major component in the Quinolizidine alkaloids.AIM OF THE STUDY:To investigate the toxic effects of SRI in rat liver BRL-3A cells and to explore potential ROS-related mechanisms.MATERIALS AND METHODS:Cell viability, cytotoxicity, apoptosis, intracellular generation of ROS, GSH/GSSG ratio and levels of proteins in mitochondria apoptosis pathway were analyzed.RESULTS:Our data indicated that SRI could suppress BRL-3A cells viability in a concentration- and time-dependent manner and increase cytotoxicity, ROS accumulation and cell apoptosis in a concentration-dependent manner. Expressions and activities of apoptotic related proteins were upregulated, whereas expression of Bcl-2 was downregulated after treatment. Furthermore, level of H2O2 was increased, whereas level of Superoxide was not changed after treatment. Moreover, the antioxidant N-acetylcysteine reversed SRI-induced apoptosis and ROS accumulation.CONCLUSION:Our data suggest that SRI promotes rat liver BRL-3A cells apoptosis by increasing intracellular ROS accumulation.

Two N-(2-(bis(pyridin-2-ylmethyl)amino)ethyl)quinoline-2-carboxamides and two N-(2-(bis(quinolin-2-ylmethyl)amino)ethyl)quinoline-2-carboxamides have been synthesized. These structures contain five nitrogen atoms that can form coordinate bonds with metal ions such as Mn(II) and Fe(II). An additional coordinating bond can be formed between the metal ion and a neutral molecule of nitric oxide (NO). The resultant complexes are potentially useful agents for targeted delivery of NO to in vivo biological sites such as tumors, where the NO is released upon irradiation with long-wavelength light. Initial work involving the synthesis and characterization of these analogues is reported here.

BACKGROUND:In view of the fact that JS-K might regulate ubiquitin E3 ligase and that ubiquitin E3 ligase plays an important role in the mechanism of CRPC formation, the goal was to investigate the probable mechanism by which JS-K regulates prostate cancer cells.METHODS:Proliferation inhibition by JS-K on prostate cancer cells was examined usingCCK-8 assays. Caspase 3/7 activity assays and flow cytometry were performed to examine whether JS-K induced apoptosis in prostate cancer cells. Western blotting and co-immunoprecipitation analyses investigated JS-K's effects on the associated apoptosis mechanism. Real time-PCR and Western blotting were performed to assess JS-K's effect on transcription of specific AR target genes. Western blotting was also performed to detect Siah2 and AR protein concentrations and co-immunoprecipitation to detect interactions of Siah2 and AR, NCoR1 and AR, and p300 and AR.RESULTS:JS-K inhibited proliferation and induced apoptosis in prostate cancer cells. JS-K increased p53 and Mdm2 concentrations and regulated the caspase cascade reaction-associated protein concentrations. JS-K inhibited transcription of AR target genes and down-regulated PSA protein concentrations. JS-K inhibited Siah2 interactions and also inhibited the ubiquitination of AR. With further investigation, JS-K was found to stabilize AR and NCoR1 interactions and diminish AR and p300 interactions.CONCLUSIONS:The present results suggested that JS-K might have been able to inhibit proliferation and induce apoptosis via regulation of the ubiquitin-proteasome degradation pathway, which represented a promising platform for the development of new compounds for PCa treatments.

The aim of the present study was to evaluate the functions of miR-200c in the regulation of tumor growth and metastasis in renal cancer cells, and to investigate the underlying mechanisms. In this study, miR-200c was up- and downregulated in two renal cancer cell lines, namely ACHN and A498, and the proliferation, colony formation, migration and invasion of the cells were measured. The expression levels of various mRNAs and proteins were then analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. It was found that miR-200c suppressed proliferation, migration and invasion of the renal cancer cells and, conversely, the inhibition of endogenous miR-200c resulted in increased cell proliferation and metastasis. Furthermore, a luciferase reporter assay revealed that miR-200c directly targeted the 3' untranslated regions of the oncogenes B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) and E2F transcription factor 3 (E2F3) mRNAs, reduced the expression of Bmi-1 and E2F3 and regulated the expression of downstream genes, including E-cadherin, N-cadherin, vimentin, p14 and p16. These results indicate a tumor suppressor role for miR-200c in renal cancer cells via the direct targeting of Bmi-1 and E2F3.

The aim of the present study was to investigate the effect of resveratrol on renal carcinoma cells and explore possible renin-angiotensin system-associated mechanisms. Subsequent to resveratrol treatment, the cell viability, apoptosis rate, cytotoxicity levels, caspase 3/7 activity and the levels of angiotensin II (AngII), AngII type 1 receptor (AT1R), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were evaluated in renal carcinoma cells. The effects of AngII, AT1R, VEGF and COX-2 on resveratrol-induced cell growth inhibition and apoptosis were also examined. The results indicated that resveratrol treatment may suppress growth, induce apoptosis, and decrease AngII, AT1R, VEGF and COX-2 levels in renal carcinoma ACHN and A498 cells. In addition, resveratrol-induced cell growth suppression and apoptosis were reversed when co-culturing with AT1R or VEGF. Thus, resveratrol may suppress renal carcinoma cell proliferation and induce apoptosis via an AT1R/VEGF pathway.

Purpose Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. Methods The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species. Results We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production. Conclusions JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.