龙葵碱体外诱导人结肠癌SW480细胞凋亡及其对相关因子的影响

  目的：观察龙葵碱对人结肠癌SW480细胞凋亡及ERK/MEK、PI3K/AKT信号通路中相关因子的影响。  方法：SW480结肠癌细胞培养后共设5组,分别为空白对照组、培养液对照组及龙葵碱不同剂量(4、8、16 mmol/L)组,各组进行相应干预。采用MTT法检测龙葵碱对结肠癌细胞株的增殖作用,流式细胞法检测龙葵碱对结肠癌细胞凋亡的影响,RT-PCR及Western blotting法检测龙葵碱处理的SW480细胞中ERK/MEK和PI3K/AKT的表达水平。  结果：MTT生长曲线显示,龙葵碱能抑制结肠癌SW480细胞株增殖。流式细胞仪检测显示,龙葵碱能够促进SW480的凋亡。RT-PCR结果显示,龙葵碱可以抑制ERK1/2 mRNA的表达。Western blotting结果表明,龙葵碱可以降低MEK/ERK和PI3K/AKT信号通路中相关蛋白的表达。  结论：龙葵碱可以抑制结肠癌细胞增殖,其对肿瘤的诱导凋亡作用可能是通过MEK/ERK和PI3K/AKT信号途径实现的。     

Inhibition of Wnt/β‐Catenin Pathway by Dehydrocostus Lactone and Costunolide in Colon Cancer Cells

Abnormal activation of β‐catenin has been reported in 90% in the sporadic and hereditary colorectal cancer. The suppression of abnormally activated β‐catenin is one of the good strategies for chemoprevention and treatment of colorectal cancer. In this study, we have isolated two main compounds from root of Saussurea lappa, dehydrocostus lactone (DCL) and costunolide (CL), and investigated their anti‐colorectal cancer activities. DCL and CL suppressed cyclin D1 and survivin through inhibiting nuclear translocation of β‐catenin. They also suppressed the nuclear translocation of galectin‐3 that is one of the coactivators of β‐catenin in SW‐480 colon cancer cells. Furthermore, DCL and CL suppressed proliferation and survival of SW‐480 colon cancer cells through the induction of cell cycle arrest and cell death. Taken together, DCL and CL from root of S. lappa have anti‐colorectal cancer activities through inhibiting Wnt/β‐catenin pathway. Copyright © 2015 John Wiley & Sons, Ltd.     

Gleditsia sinensis thorn extract inhibits human colon cancer cells: the role of ERK1/2, G2/M‐phase cell cycle arrest and p53 expression

The thorns of Gleditsia sinensis are used as a medicinal herb in China and Korea. However, the mechanisms responsible for the antitumor effects of the water extract of Gleditsia sinensis thorns (WEGS) remain unknown. HCT116 cells treated with the WEGS at a dose of 800 μg/mL (IC₅₀) showed a significant decrease in cell growth and an increase in cell cycle arrest during the G2/M‐phase. G2/M‐phase arrest was correlated with increased p53 levels and down‐regulation of the check‐point proteins, cyclinB1, Cdc2 and Cdc25c. In addition, treatment with WEGS induced phosphorylation of extracellular signal‐regulated kinase (ERK), p38 MAP kinase and JNK (c‐Jun N‐terminal kinases). Moreover, inhibition of ERK by treatment of cells with the ERK‐specific inhibitor PD98059 blocked WEGS‐mediated p53 expression. Similarly, blockage of ERK function in the WEGS‐treated cells reversed cell‐growth inhibition and decreased cell cycle proteins. Finally, in vivo WEGS treatment significantly inhibited the growth of HCT116 tumor cell xenografts in nude mice with no negative side effects, including loss of body weight. These results describe the molecular mechanisms whereby the WEGS might inhibit proliferation of colon cancer both in vitro and in vivo, suggesting that WEGS has potential as an anticancer agent for the treatment of malignancies. Copyright © 2010 John Wiley & Sons, Ltd.     

人参皂苷CK抑制人结肠癌SW480细胞增殖的机制研究

目的研究人参皂苷CK对人结肠癌SW480细胞增殖及凋亡的影响,并进一步探讨其作用机制。方法采用CCK-8法检测细胞活力;通过流式细胞术检测细胞周期、细胞凋亡、活性氧(ROS)水平和线粒体膜电位(MMP)变化;Hoechst染色检测细胞凋亡;蛋白免疫印迹法检测细胞色素C(CytC)释放以及凋亡相关蛋白Bcl-2、Bax和cleaved Caspase-3等的表达。结果人参皂苷CK对SW480细胞的增殖有显著抑制作用。人参皂苷CK诱导SW480细胞周期阻滞于G0/G1期,促进细胞发生早期凋亡。人参皂苷CK可以显著增加细胞内ROS水平,降低MMP水平;人参皂苷CK促进Bax和cleaved Caspase-3的表达,抑制Bcl-2的表达。此外,人参皂苷CK使SW480细胞内CytC大量释放。结论人参皂苷CK对SW480细胞的增殖具有显著的抑制作用,其作用机制可能是通过促进线粒体超氧化物升高,导致胞内ROS水平显著增加和MMP显著下降,进而导致CytC释放,上调Bax的表达,下调Bcl-2的表达,最终导致细胞发生凋亡。     

Dual inhibition of EGFR and MET by Echinatin retards cell growth and induces apoptosis of lung cancer cells sensitive or resistant to gefitinib

Patients with non‐small‐cell lung cancer (NSCLC) containing epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to tyrosine kinase inhibitor gefitinib; however, the treatment is less effective over time. Gefitinib resistance mechanisms include MET gene amplification. A therapeutic strategy targeting MET as well as EGFR can overcome resistance to gefitinib. In the present study we identified Echinatin (Ecn), a characteristic chalcone in licorice, which inhibited both EGFR and MET and strongly altered NSCLC cell growth. The antitumor efficacy of Ecn against gefitinib‐sensitive or –resistant NSCLC cells with EGFR mutations and MET amplification was confirmed by suppressing cell proliferation and anchorage‐independent colony growth. During the targeting of EGFR and MET, Ecn significantly blocked the kinase activity, which was validated with competitive ATP binding. Inhibition of EGFR and MET by Ecn decreases the phosphorylation of downstream target proteins ERBB3, AKT and ERK compared with total protein expression or control. Ecn induced the G2/M cell cycle arrest, and apoptosis via the intrinsic pathway of caspase‐dependent activation. Ecn induced ROS production and GRP78, CHOP, DR5 and DR4 expression as well as depolarized the mitochondria membrane potential. Therefore, our results suggest that Ecn is a promising therapeutic agent in NSCLC therapy.     

Naphthoquinone Components from Alkanna tinctoria (L.) Tausch Show Significant Antiproliferative Effects on Human Colorectal Cancer Cells

Our research to seek active compounds against human colorectal cancer from the root of Alkanna tinctoria (L.) Tausch led to the isolation of two naphthoquinones, alkannin (1) and angelylalkannin (2). The antiproliferative effects of the two compounds on human colon cancer cells HCT‐116 and SW‐480 were determined by the 3,4‐(5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium salt (MTS) method. Cell cycle profile and cell apoptosis were determined using flow cytometry. Both of the two compounds showed significant inhibitory effects on the cancer cells. For alkannin (1) and angelylalkannin (2), the median inhibitory concentration (IC₅₀) values were 2.38 and 4.76 µ m for HCT‐116 cells, while for SW‐480 cells they were 4.53 and 7.03 µ m , respectively. The potential antiproliferative mechanisms were also explored. At concentrations between 1–10 µ m , both compounds arrested the cell cycle at the G1 phase and induced cell apoptosis. Copyright © 2012 John Wiley & Sons, Ltd.     

Carvacrol induces cytotoxicity in human cervical cancer cells but causes cisplatin resistance: Involvement of MEK–ERK activation

Carvacrol has been shown to possess anticancer activity, but the mechanism is unknown, as well as the possibility of interaction with anticancer drugs. The aim of this study was to investigate the role of mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK) signaling in carvacrol‐induced human cervical cancer HeLa cell cytotoxicity. In addition, we studied sensitization of HeLa cells to cisplatin (CP) by carvacrol. Both carvacrol and CP showed dose‐dependent cytotoxicity against HeLa cells and activated ERK1/2. The MEK inhibitor PD325901 suppressed ERK expression and further increased cytotoxicity of carvacrol but increased viability of CP‐treated cells by modulating apoptosis. The MEK inhibitor also increased microtubule‐associated protein 1A/1B‐light chain 3 beta expression in CP treatment. Cotreatment with CP and carvacrol resulted in increased viability of the cancer cells compared with CP treatment, which was associated with the suppression of apoptosis. MEK inhibition decreased the cell viability, without changes in apoptosis. Concomitantly, carvacrol increased CP‐induced expression of light chain 3 beta, which was enhanced by MEK inhibition. The results of the current study suggest the opposite role of ERK1/2 in carvacrol and CP‐induced HeLa cell cytotoxicity. Interestingly, carvacrol induced CP resistance in HeLa cells through ERK1/2‐independent suppression of apoptosis and ERK1/2‐dependent modulation of autophagy.     

Synergistic effect of berberine and HMQ1611 impairs cell proliferation and migration by regulating Wnt signaling pathway in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a biologically complex disease. Combination chemotherapy is a good strategy after surgery treatment. In this study, we report that berberine combined with HMQ1611 (BCH) had a good synergistic effect on the HCC. Our findings concluded that BCH showed good inhibition on the HCC proliferation and colony formation, which attributed to cell cycle arrest by BCH at G1 phase through impairing the expression of cyclinD1, cyclinE, and cdc2 and downregulated the phosphorylation of Akt, mTOR, and ERK. Moreover, BCH negatively regulated Wnt signaling pathway by upregulating the Axin and inhibiting the nuclear translocation of β‐catenin. BCH suppressed the phosphorylation of LRP5/6, GSK3β, the expression of Wnt5a, Frizzled8, CK1, and APC, as well as the nucleus protein included MMP2, MMP3, MMP9, and c‐myc. The above data of Wnt signaling regulators contributed to inhibition by BCH on cell migration. In vivo studies, BCH significantly suppressed the growth of SMMC‐7721 xenograft tumors through downregulating Ki67 and β‐catenin, as well as upregulating Axin and p‐β‐catenin. In conclusion, the results revealed that BCH exhibited potential antitumor activities against human liver cancer in vitro and in vivo, and the potential mechanism underlying these activities depended on the inhibition of the Wnt/β‐catenin signaling pathway.     

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

Ganoderic Acid A (GAA) is often applied for healing cardiovascular and cerebrovascular ailments, but the influences in cerebral ischemia injury are still hazy. The research delved into the functions of GAA in hypoxia‐triggered impairment in PC12 cells. PC12 cells received hypoxia management for 12 hr, and subsequently, cell viability, migration, apoptosis, and correlative protein levels were assessed. After preprocessing with GAA, above cell behaviors were monitored again. The vector of microRNA (miR)‐153 inhibitor was utilized for PC12 cell transfection to further explore the functions of miR‐153 in hypoxia‐impaired cells. Pathways of phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were investigated via executing western blot for uncovering the latent mechanism. Results revealed that hypoxia disposition triggered PC12 cells impairment via restraining cell viability and migration and accelerating apoptosis. However, GAA visibly mollified hypoxia‐provoked impairment in PC12 cells. Interestingly, the enhancement of miR‐153 triggered by GAA was observed in hypoxia‐impaired PC12 cells. After miR‐153 inhibitor transfection, the protective functions of GAA in hypoxia‐impaired PC12 cells were dramatically inversed. Furthermore, GAA caused PI3K/AKT and mTOR activations via enhancement of miR‐153 in hypoxia‐impaired PC12 cells. The findings evinced that GAA exhibited the protective functions in PC12 cells against hypoxia‐evoked impairment through activating PI3K/AKT and mTOR via elevating miR‐153.     

Anti‐Proliferative Effects of Polyphenols from Pomegranate Rind (Punica granatum L.) on EJ Bladder Cancer Cells Via Regulation of p53/miR‐34a Axis

miRNAs and their validated miRNA targets appear as novel effectors in biological activities of plant polyphenols; however, limited information is available on miR‐34a mediated cytotoxicity of pomegranate rind polyphenols in cancer cell lines. For this purpose, cell viability assay, Realtime quantitative PCR for mRNA quantification, western blot for essential protein expression, p53 silencing by shRNA and miR‐34a knockdown were performed in the present study. EJ cell treatment with 100 µg (GAE)/mL PRE for 48 h evoked poor cell viability and caspase‐dependent pro‐apoptosis appearance. PRE also elevated p53 protein and triggered miR‐34a expression. The c‐Myc and CD44 were confirmed as direct targets of miR‐34a in EJ cell apoptosis induced by PRE. Our results provide sufficient evidence that polyphenols in PRE can be potential molecular clusters to suppress bladder cancer cell EJ proliferation via p53/miR‐34a axis. Copyright © 2015 John Wiley & Sons, Ltd.     

Retracted: Bilobalide alleviates tumor necrosis factor‐alpha‐induced pancreatic beta‐cell MIN6 apoptosis and dysfunction through upregulation of miR‐153

Type 1 diabetes mellitus (T1DM) is a systemic disease and one classical type of total DM. Bilobalide (BB) is constituted of EGb 761. Our purpose was identifying the role of BB in TIDM in the current study. MIN6 cells were treated by TNF‐α; then, viability, apoptosis, and insulin secretion were assessed by performing Cell Counting Kit‐8 assay, flow cytometry, glucose‐stimulated insulin secretion assay, and western blot. The effects of BB were assessed to identify its function. Further, the above mentioned parameters were reassessed when silencing miR‐153. TNF‐α declined viability and insulin secretion as well as raised apoptosis and inducible nitric oxide synthase (iNOS) expression in MIN6 cells. BB alleviated the apoptosis and dysfunction induced by TNF‐α. MiR‐153 expression was elevated by BB when induced by TNF‐α. Increase of viability and insulin secretion as well as decline of apoptosis and iNOS induced by BB treatment was alleviated by silencing miR‐153. The rates of p/t‐p70S6K, p/t‐mammalian target of rapamycin (mTOR) and p/t‐adenosine monophosphate‐activated protein kinase (AMPK) were raised by BB and suppressed by silencing miR‐153 under TNF‐α induced condition. BB raised viability and insulin secretion, declined apoptosis and iNOS expression by up‐regulating miR‐153. Furthermore, BB activated AMPK/mTOR pathway by up‐regulating miR‐153.     

Baicalein enhances the antitumor efficacy of docetaxel on nonsmall cell lung cancer in a β‐catenin‐dependent manner

The side effects of docetaxel have limited its antitumor performances in the treatment of nonsmall cell lung cancer (NSCLC). To address the problem, baicalein, a bioactive flavone that exhibits antitumor activity, was combined with docetaxel so as to achieve better efficacy and lower toxicity. The combination treatment enhanced the stabilization of microtubules and halted the cell‐cycle progression, thus synergistically inhibiting the proliferation and inducing the apoptosis of A549 cells and Lewis lung carcinoma cells. The decreased expression of Cyclin‐dependent kinase 6 and Cyclin B1 confirmed its regulation in cell cycle, with β‐catenin being an important upstream effector, as evidenced by the decreased expression in the cytoplasm and nucleus as well as the attenuated aggregation in the nucleus. Furthermore, baicalein plus docetaxel evinced better antitumor efficacy by the suppressed tumor growth, increased apoptosis, and decreased tumor angiogenesis in vivo, with no increased toxicity discovered in both tumor‐bearing and non‐tumor‐bearing mice, and an improvement in therapeutic index. This study has demonstrated that baicalein plus docetaxel is an appropriate combination simultaneously with augmented antitumor efficacy and acceptable safety, which might be a promising strategy for patients with advanced NSCLC.     

Alkaloids from nux vomica suppresses colon cancer cell growth through Wnt/β‐catenin signaling pathway

Brucine and Strychnine are alkaloids isolated from the seeds of Strychnos nux vomica L., which have long been used as a traditional medicine for the treatment of tumor. However, the effect of Brucine and Strychnine on colorectal cancer (CRC) and the underlying molecular mechanism remain unclear. In the present study, Brucine and Strychnine displayed profound inhibitory effects on the growth of human colon cancer cells. The results of flow cytometric analysis demonstrated that the two alkaloids induced cellular apoptosis. Moreover, the growth of DLD1 xenografted tumors in nude mice was significantly suppressed in the Brucine or Strychnine treated group. Mechanistically, the Wnt/β‐catenin is involved in this phenomenon, which is characterized by significantly increased expression of DKK1 and APC, whereas decreased expression of β‐catenin, c‐Myc, and p‐LRP6 in CRC cells as well as tumor tissues. Collectively, Brucine and Strychnine have targeted inhibition for colon cancer proliferation both in vitro and in vivo, and it is valuable for future exploitation and utilization as an antitumor agent of CRC.     

Celastrol inhibits growth and metastasis of human gastric cancer cell MKN45 by down‐regulating microRNA‐21

Celastrol could inhibit cancer cell growth in vitro. However, effect(s) of celastrol on gastric cancer is not well studied. Therefore, we investigated the effects of celastrol on human gastric cancer cell line MKN45 and the underlying mechanisms. We found that celastrol inhibited cell proliferation, migration, and invasion and induced cell apoptosis and G2/M cell cycle arrest (p < .05, p < .01, or p < .001). Under celastrol treatment, overexpression of microRNA‐21 (miR‐21) increased cell viability, migration, and invasion and inhibited cell apoptosis compared with negative control (p < .05, p < .01, or p < .001). In addition, the phosphorylation of PTEN was significantly up‐regulated, whereas PI3K, AKT, p65, and IκBα phosphorylation was statistically decreased by celastrol (p < .05 or p < .01) and then further reversed by miR‐21 overexpression (p < .05 or p < .01). On the other side, miR‐21 silence showed contrary results (p < .05) as relative to miR‐21 overexpression. In conclusion, celastrol inhibits proliferation, migration, and invasion and inactivates PTEN/PI3K/AKT and nuclear factor κB signaling pathways in MKN45 cells by down‐regulating miR‐21.     

Breviscapine‐induced apoptosis of human hepatocellular carcinoma cell line HepG2 was involved in its antitumor activity

Breviscapine is a flavonoid constituent isolated from a traditional Chinese herb Erigerin breviscapus (Vant.) Hand‐Mazz. To investigate the apoptosis‐inducing effect of breviscapine on human hepatocellular carcinoma cell line HepG2 and explore the relative molecular mechanisms. HepG2 cells were treated with breviscapine at different concentrations and the inhibitory rate was analyzed by MTT assay. The morphological changes in cells were observed under an inverted light microscope and a fluorescence microscope and the apoptosis rate were detected by flow cytometry. Western blot was used to evaluate the protein expression. The viability of HepG2 cells was markedly inhibited in a concentration‐dependent manner and obvious morphological changes were confirmed, including condensed chromatin and reduction in volume. The increased percentage of apoptotic cells was displayed by flow cytometry and the altered expression level of several apoptosis‐associated proteins, Bcl‐2, Bax and caspase‐3, was detected by western blot. It is first discovered that breviscapine exhibited potential antitumor activity, induces remarkable apoptosis in HepG2 cells and promises to be a new candidate in future cancer therapy. Copyright © 2010 John Wiley & Sons, Ltd.     

Curcumin inhibits cell viability,migration, and invasion of thymic carcinoma cells via downregulation of microRNA‐27a

Curcumin (CUR) is a kind of polyphenolic compound and widely used in the treatment of diseases. However, the involvement of CUR in thymic carcinoma remains unknown. The object of our research is to clarify the role of CUR and related regulatory mechanism in thymic carcinoma cells. After treatment with CUR for 24 hr, cell viability, apoptosis, migration, and invasion of TC1889 cells were measured. Real‐time polymerase chain reaction was executed to examine the expression of microRNA‐27a (miR‐27a) in thymic carcinoma tissues and TC1889 cells. After miR‐27a mimic transfection, whether miR‐27a is involved in CUR‐modulated cell behaviors was measured. Finally, western blot was utilized to detect mTOR and Notch 1 pathways‐linked proteins. CUR restrained cell viability and increased cell apoptosis of TC1889 cells. In addition, cell migration and invasion were restrained by CUR. Meanwhile, miR‐27a expression was positively regulated in thymic carcinoma tissues and downregulated by CUR in TC1889 cells. Overexpressed miR‐27a reversed the CUR‐induced reduction of growth, migration, and invasion in TC1889 cells. Furthermore, CUR blocked mTOR and Notch 1 pathways via downregulating miR‐27a. We demonstrated that CUR blocked mTOR and Notch 1 pathways via downregulating miR‐27a, thereby suppressing cell growth, migration, and invasion of thymic carcinoma cells.     

Acacetin‐induced cell apoptosis in head and neck squamous cell carcinoma cells: Evidence for the role of muscarinic M3 receptor

Aacacetin, a plant flavone has shown antitumor efficacy recently. However, its associated mechanisms are poorly known. We hypothesized that the muscarinic M3 receptor (M₃R), which is highly expressed in some cancer tissue, is related to the antitumor effect of acacetin in head and neck squamous cell carcinoma (HNSCC) cells. Our results showed that 12.5‐ to 200‐μM acacetin inhibited cell viability in dose‐ and time‐dependent manners in HNSCC cells, but a relative higher concentration was needed for oral adenoid cystic carcinoma cells. M₃R expression level was higher in HNSCC cells than that in adenoid cystic carcinoma cells. Flow cytometry and electron microscopy confirmed acacetin‐induced cell apoptosis in 22B cells, a HNSCC cell line. Acacetin promoted mitochondrial cytochrome c release and caspase 9, 3 processing. Knocking down of M₃R expression by specific siRNA significantly prevented the acacetin‐induced cell viability damage, cell apoptosis, and caspase 3 activation. Besides, M₃R was also involved in acacetin‐induced elevation of reactive oxygen species and intracellular calcium ([Ca²⁺]_i). These data indicate that acacetin‐induced cell apoptosis in HNSCC cells may through M₃R related calcium signaling and caspase 3 activation. Acacetin is a potent natural antitumor reagent especially for the tumor cells, which highly expressed M₃R.     

木犀草素抑制人胃癌BGC-823细胞增殖作用的研究

目的研究木犀草素(Luteolin,Lu)对人胃癌BGC-823细胞增殖的体外抑制作用及其机制。方法 DPPH法测定Lu抗氧化活性;MTT法测定Lu对BGC-823细胞增殖的影响;流式细胞术检测细胞周期分布影响及诱导凋亡的作用;倒置显微镜下观察细胞形态学变化。结果 Lu清除自由基的能力与其浓度呈正相关(r2=0.979);5,10,20,40μmol/L的Lu作用48 h后对BGC-823细胞增殖抑制率分别为5.08%,7.09%,25.27%和53.77%,半数抑制浓度(IC50)为(37.88±5.81)μmol/L;Lu以浓度依赖性阻滞细胞周期在G2/M期,且S期细胞比例呈下降趋势。40μmol/L的Lu作用72 h后,BGC-823细胞凋亡率显著增高(P<0.01);镜下观察发现经Lu处理后细胞固缩并伴随细胞膜破裂的现象。结论 Lu在体外对人胃癌BGC-823细胞增殖有明显的抑制作用,且呈剂量依赖性;抗氧化、改变细胞周期及诱导细胞凋亡是其抗肿瘤作用的机制。     

Ganoderma lucidum extract induces G1 cell cycle arrest, and apoptosis in human breast cancer cells

Ganoderma lucidum (Fr.) Karst is a traditional Chinese herb that has been widely used for centuries to treat various diseases including cancer. Herein, an ethanol-soluble and acidic component (ESAC), which mainly contains triterpenes, was prepared from G. lucidum and its anti-tumor effects in vitro were tested on human breast cancer cells. Our results showed that ESAC reduced the cell viability of MCF-7 and MDA-MB-231 cells in a concentration-dependent manner with IC(50) of about 100 μg/mL and 60 μg/mL, respectively. DNA damage was detected by Comet assay and the increased expression of γ-H2AX after ESAC treatment was determined in MCF-7 cells. Moreover, ESAC effectively mediated G1 cell cycle arrest in both concentration- and time-dependent manners and induced apoptosis as determined by Hoechst staining, DNA fragment assay and Western blot analysis in MCF-7 cells. In conclusion, ESAC exerts anti-proliferation effects by inducing DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells.