Hepatoprotective potential of a novel quinazoline derivative in thioacetamide-induced liver toxicity.

Purpose: The compound quinazoline Q-Br, 3-(5-bromo-2-hydroxybenzylideneamino)-2-(5-bromo-2 hydroxyphenyl) 2,3-dihydroquinazoline-4(1H)-one (Q-Br) was evaluated for its antioxidant capacity and potential hepatoprotectivity against sub-chronic liver toxicity induced by thioacetamide in rats. Materials and Methods: Rats were assigned into five groups; healthy (normal) and cirrhosis control groups were given 5% Tween 20 orally, the reference control group was given a Silymarin dose of 50 mg/kg, and low-dose Q-Br and high-dose Q-Br groups were given a daily dose of 25 mg/kg and 50 mg/g Q-Br, respectively. Liver status was detected via fluorescence imaging with intravenous injection of indocyanine green (ICG) and a plasma ICG clearance test. Liver malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were also tested. The degree of fibrosis was determined histologically by hematoxylin and eosin and Masson's Trichrome staining. The immunohistochemistry of liver tissue inhibitor of metalloproteinase (TIMP-1), matrix metalloproteinase (MMP-2), and alpha-smooth muscle actin (α-SMA) was performed. Results: Q-Br recorded mild antioxidant capacity, dose-dependent improvement in the liver status, and inhibition of oxidative stress compared to cirrhosis control. Histopathology notified a remarkable reduction in the degree of fibrosis. Immunohistochemistry revealed an obvious low expression of MMP-2 and α-SMA along with a higher expression of TIMP-1 in Q-Br- and Silymarin-treated livers. Conclusion: Q-Br treatment altered the course of toxicity induced by thioacetamide suggesting significant hepatoprotective potential of Q-Br treatment.

Retraction Note: Acute Toxicity and Gastroprotection Studies of a New Schiff Base Derived Manganese (II) Complex against HCl/Ethanol-Induced Gastric Ulcerations in Rats.

This paper has been retracted.

Synthesis of Novel Derivatives of Quinazoline Schiff base Compound Promotes Epithelial Wound Healing.

Quinazoline is an aromatic bicyclic compound exhibiting several pharmaceutical and biological activities. This study was conducted to investigate the potential wound healing properties of Synthetic Quinazoline Compound (SQC) on experimental rats. The toxicity of SQC was determined by MTT cell proliferation assay. The healing effect of SQC was assessed by in vitro wound healing scratch assay on the skin fibroblast cells (BJ-5ta) and in vivo wound healing experiment of low and high dose of SQC on adult Sprague-Dawley rats compared with negative (gum acacia) and positive control (Intrasite-gel). Hematoxylin and Eosin (H&E), Masson's Trichrome (MT) staining and immunohistochemistry analysis were performed to evaluate the histopathological alterations and proteins expression of Bax and Hsp70 on the wound tissue after 10 days. In addition, levels of antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase), and malondialdehyde (MDA) were measured in wound tissue homogenates. The SQC significantly enhanced BJ-5ta cell proliferation and accelerated the percentage of wound closure, with less scarring, increased fibroblast and collagen fibers and less inflammatory cells compared with the negative control. The compound also increases endogenous enzymes and decline lipid peroxidation in wound homogenate.

Synthesis and biological study of acridine-based imidazolium salts.

A new series of acridine based imidazolium salts was synthesized and evaluated for in vitro cytotoxicity against human cancer cell lines by an MTT assay. The synthesis applied a coupling of imidazoles with 9-chloroacridines, which originated from an Ullmann condensation of a 2-chloro-benzoic acid with an aniline. The target compounds were obtained in high yields. The DPPH assay indicated considerable antioxidant activity for target compounds with simple and short alkyl chains on the imidazole, while increasing chain length and the introduction of an additional π-electron system in most cases reduced the activity. All compounds exhibited low biotoxicity against non-cancerous cell lines, whereas a few compounds showed promising anticancer activity. Unlike for the reference drugs Tamoxifen and Paclitaxel, the anticancer activity of acridine imidazolium ions is specific for only selected cancer types. Reasonable fluorescent behaviour of the products provide potential for visualization of the distribution of active drugs in tissue.

Correction: The Gastroprotective Effect of Vitex pubescens Leaf Extract against Ethanol-Provoked Gastric Mucosal Damage in Sprague-Dawley Rats.

[This corrects the article DOI: 10.1371/journal.pone.0157431.].

Corrigendum: Apoptotic effect of novel Schiff Based CdCl2(C14H21N3O2) complex is mediated via activation of the mitochondrial pathway in colon cancer cells.

This corrects the article DOI: 10.1038/srep09097.

Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats.

Actinodaphne sesquipedalis Hook. F. Var. Glabra (Kochummen), also known as "Medang payung" by the Malay people, belongs to the Lauraceae family. In this study, methanol leaf extract of A. sesquipedalis was investigated for their acute toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by ethanol. The rats were assigned to one of five groups: normal group (group 1), ulcer group (group 2), control positive drug group (group 3) and two experimental groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract. The rats were sacrificed an hour after pretreatment with extracts, and their stomach homogenates and tissues were collected for further evaluation. Macroscopic and histological analyses showed that gastric ulcers in rats pretreated with the extract were significantly reduced to an extent that it allowed leukocytes penetration of the gastric walls compared with the ulcer group. In addition, an ulcer inhibition rate of >70% was detected in rats treated with both doses of A. sesquipedalis extract, showing a notable protection of gastric layer. Severe destruction of gastric mucosa was prevented with a high production of mucus and pH gastric contents in both omeprazole-treated and extract-treated groups. Meanwhile, an increase in glycoprotein uptake was observed in pretreated rats through accumulation of magenta color in Periodic Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione, prostaglandin E2, superoxide dismutase and protein concentration levels in comparison with group 2. Suppression of apoptosis in gastric tissues by upregulation of Hsp70 protein and downregulation of Bax protein was also observed in rats pretreated with extract. Consistent results of a reduction of gastric ulcer and the protection of gastric wall were obtained for rats pretreated with A. sesquipedalis extract, which showed its prominent gastroprotective potential in rats' stomach against ethanol-induced ulcer.

The antiulcer effect of Cibotium barometz leaves in rats with experimentally induced acute gastric ulcer.

Cibotium barometz is a pharmaceutical plant customarily used in traditional medicine in Malaysia for the treatment of different diseases, such as gastric ulcer. The gastroprotective effect of C. barometz leaves against ethanol-induced gastric hemorrhagic abrasions in Sprague Dawley rats has been evaluated in terms of medicinal properties. Seven groups of rats (normal control and ulcerated control groups, omeprazole 20 mg/kg, 62.5, 125, 250, and 500 mg/kg of C. barometz correspondingly) were used in antiulcer experiment and pretreated with 10% Tween 20. After 1 hour, the normal group was orally administered 10% Tween 20, whereas absolute alcohol was fed orally to ulcerated control, omeprazole, and experimental groups. Gastric's homogenate were assessed for endogenous enzymes activities. Stomachs were examined macroscopically and histologically. Grossly, the data demonstrated a significant decrease in the ulcer area of rats pretreated with plant extract in a dose-dependent manner with respect to the ulcerated group. Homogenates of the gastric tissue exhibited significantly increased endogenous enzymes activities in rats pretreated with C. barometz extract associated with the ulcerated control group. Histology of rats pretreated with C. barometz extract group using hematoxylin and eosin staining exhibited a moderate-to-mild disruption of the surface epithelium with reduction in submucosal edema and leucocyte infiltration in a dose-dependent manner. In addition, it showed heat shock protein70 protein up-expression and BCL2-associated X protein downexpression. These outcomes might be attributed to the gastroprotective and antioxidative effects of the plant.

Synthesis and Characterization of a New Benzoindole Derivative with Apoptotic Activity Against Colon Cancer Cells.

BACKGROUND: Colorectal cancer is the third most common form of cancer in both men and women around the world. The chemistry and biological study of heterocyclic compounds have been an interesting area for a long time in pharmaceutical and medicinal chemistry. METHODS: A new synthetic compound, 2-(1,1-dimethyl-1H-benzo[e]indol-2-yl)-3-((2-hydroxyphenyl)amino) acrylaldehyde, abbreviated as DBID, was prepared through the reaction of 2-(diformylmethylidene)-1,1- dimethylbenzo[e]indole with 2-aminophenol. The chemical structure of the synthesized compound was characterized by 1H NMR, 13C NMR and APT-NMR spectroscopy and confirmed by elemental analysis (CHN). The compound was screened for the antiproliferation effect against colorectal cancer cell line, HCT 116 and its possible mechanism of action was elucidated. To determine the IC50 value, the MTT assay was used and its apoptosisinducing effect was investigated. RESULTS: DBID inhibited the proliferation of HCT 116 cells with an IC50 of 9.32 µg/ml and significantly increased the levels of caspase -8, -9 and -3/7 in the treated cells compared to untreated cells. Apoptosis features in HCT 116 cell was detected in treated cells by using the AO/PI staining that confirmed that the cells had undergone remarkable morphological changes in apoptotic bodies. Furthermore, this changes in expression of caspase -8, -9 and -3 were confirmed by gene and protein quantification using RT-PCR and western blot analysis, respectively. CONCLUSION: The current study showed that the DBID compound has demonstrated chemotherapeutic activity which was evidenced by significant increases in the expression and activation of caspase and exploit the apoptotic signaling pathways to trigger cancer cell death.

Kelussia odoratissima Mozaff. activates intrinsic pathway of apoptosis in breast cancer cells associated with S phase cell cycle arrest via involvement of p21/p27 in vitro and in vivo.

BACKGROUND: The aim of this study was to evaluate the anticancer potential of Kelussia odoratissima. Several in vitro and in vivo biological assays were applied to explore the direct effect of an extract and bioactive compound of this plant against breast cancer cells and its possible mechanism of action. MATERIALS AND METHODS: K. odoratissima methanol extract (KME) was prepared, and MTT assay was used to evaluate the cytotoxicity. To identify the cytotoxic compound, a bioassay-guided investigation was performed on methanol extract. 8-Hydroxy-ar-turmerone was isolated as a bioactive compound. In vivo study was performed in the breast cancer rat model. LA7 cell line was used to induce the breast tumor. Histopathological and expression changes of PCNA, Bcl-2, Bax, p27 and p21 and caspase-3 were examined. The induction of apoptosis was tested using Annexin V-fluorescein isothiocyanate (FITC) assay. To confirm the intrinsic pathway of apoptosis, caspase-7 and caspase-9 assays were utilized. In addition, cell cycle arrest was evaluated. RESULTS: Our results demonstrated that K. odoratissima has an obvious effect on the arrest of proliferation of cancer cells. It induced apoptosis, transduced the cell death signals, decreased the threshold of mitochondrial membrane potential (MMP), upregulated Bax and downregulated Bcl-2. CONCLUSION: This study demonstrated that K. odoratissima exhibits antitumor activity against breast cancer cells via cell death and cell cycle arrest.

Identification of 5-Methoxy-2-(Diformylmethylidene)-3,3-Dimethylindole as an Anti-Influenza A Virus Agent.

Influenza virus is estimated to cause 3-5 million severe complications and about 250-500 thousand deaths per year. Different kinds of anti-influenza virus drugs have been developed. However, the emergence of drug resistant strains has presented a big challenge for efficient antiviral therapy. Indole derivatives have been shown to exhibit both antiviral and anti-inflammatory activities. In this study, we adopted a cell-based system to screen for potential anti-IAV agents. Four indole derivatives (named 525A, 526A, 527A and 528A) were subjected to the antiviral screening, of which 526A was selected for further investigation. We reported that pre-treating cells with 526A protects cells from IAV infection. Furthermore, 526A inhibits IAV replication by inhibiting the expression of IAV genes. Interestingly, 526A suppresses the activation of IRF3 and STAT1 in host cells and thus represses the production of type I interferon response and cytokines in IAV-infected cells. Importantly, 526A also partially blocks the activation of RIG-I pathway. Taken together, these results suggest that 526A may be a potential anti-influenza A virus agent.

The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats.

BACKGROUND: Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups. After 60 min, the normal control group of rats was orally administered 10% Tween 20, while absolute ethanol was orally administered to the groups of ulcer control, omeprazole and experimental groups. Stomachs of the rats were examined macroscopically and histologically. Homogenates of stomachs were used to evaluate endogenous antioxidant enzyme activities. RESULTS: Rats pre-fed with plant extract presented a significant decrease in the sore area, increased pH of gastric contents and preserved stomach wall mucus compared to the ulcer group. Histologically, rats pre-fed with C. barometz hair extract showed mild to moderate disruptions of the surface epithelium while animals pre-fed with absolute ethanol showed severe disruptions of the stomach epithelium with edema and leucocyte penetration of the submucosal layer. A Periodic acid Schiff (PAS) staining revealed that each rat pre-treated with the plant extract displayed an intense uptake of stomach epithelial glycoprotein magenta color compared to the ulcer control group. Immunohistochemical analysis revealed that rats pre-fed with the plant extract showed an up-regulation of the heat shock protein 70 (HSP70) and down-regulation of Bax proteins compared to ulcer control rats. Homogenates of the stomach tissue demonstrated significant increases in the endogenous antioxidant enzymatic activity and decreased lipid peroxidation (MDA) in rats pre-treated with C. barometz hair extract compared with the ulcer control rats. In acute toxicity, the liver and kidney revealed no hepatotoxic or nephrotoxic effects histologically. CONCLUSIONS: The gastric cytoprotective action of C. barometz hair extract might be attributed to antioxidants, an increase in gastric pH, stomach mucus preservation, increased endogenous antioxidant enzymes, decreased lipid peroxidation, up-regulation of HSP70 and down-regulation of Bax proteins.

Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells.

In the present study, we examined the cytotoxic effects of Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, and C1 on MDA-MB-231 cells and derived breast cancer stem cells from MDA-MB-231 cells. The acute toxicity experiment with compound C1 revealed no cytotoxic effects on rats. Fluorescent microscopic studies using Acridine Orange/Propidium Iodide (AO/PI) staining and flow cytometric analysis using an Annexin V probe confirmed the occurrence of apoptosis in C1-treated MDA-MB-231 cells. Compound C1 triggered intracellular reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) releases in treated MDA-MB-231 cells. The Cellomics High Content Screening (HCS) analysis showed the induction of intrinsic pathways in treated MDA-MB-231 cells, and a luminescence assay revealed significant increases in caspase 9 and 3/7 activity. Furthermore, flow cytometric analysis showed that compound C1 induced G0/G1 arrest in treated MDA-MB-231 cells. Real time PCR and western blot analysis revealed the upregulation of the Bax protein and the downregulation of the Bcl-2 and HSP70 proteins. Additionally, this study revealed the suppressive effect of compound C1 against breast CSCs and its ability to inhibit the Wnt/ß-catenin signaling pathways. Our results demonstrate the chemotherapeutic properties of compound C1 against breast cancer cells and derived breast cancer stem cells, suggesting that the anticancer capabilities of this compound should be clinically assessed.

The Gastroprotective Effect of Vitex pubescens Leaf Extract against Ethanol-Provoked Gastric Mucosal Damage in Sprague-Dawley Rats.

Vitex pubescens is a Malaysian therapeutic plant employed in traditional drug to remedy a variety of disorders. The purpose of this research is to assess the gastroprotective efficiency of V. pubescens leaves against ethanol-induced gastric hemorrhagic laceration in rats. Animals were randomly allocated into seven groups and pre-treated, separately, with 10% Tween 20 (normal and ulcer control groups), 20 mg/kg omeprazole (reference group), and 62.5, 125, 250, and 500 mg/kg of V. pubescens extract (experimental groups). All animals were sacrificed after another hour. Histological evaluation of the ulcer control group revealed significant injury to the gastric mucosa with edema and leucocyte infiltration of the submucosal layer. PAS staining, showed remarkably intense magenta color, remarkable increase of HSP70 and decrease of Bax proteins in rats pre-treated with plant extracts compared to the ulcer control group. Gastric homogenates revealed a remarkable increase in endogenous antioxidant enzyme activities (CAT, SOD, GSH) and a decrease in the lipid peroxidation level (MDA) in animals pre-treated with V. pubescens extract compared with the ulcer control group. The gastroprotective activity of this plant might be related to increased antioxidant enzymes and decrease lipid peroxidation upsurge of HSP70 and reduced expression of Bax proteins.

Monobenzyltin Complex C1 Induces Apoptosis in MCF-7 Breast Cancer Cells through the Intrinsic Signaling Pathway and through the Targeting of MCF-7-Derived Breast Cancer Stem Cells via the Wnt/ß-Catenin Signaling Pathway.

Monobenzyltin Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, C1, is an organotin non-platinum metal-based agent. The present study was conducted to investigate its effects on MCF-7 cells with respect to the induction of apoptosis and its inhibitory effect against MCF-7 breast cancer stem cells. As determined in a previous study, compound C1 revealed strong antiproliferative activity on MCF-7 cells with an IC50 value of 2.5 µg/mL. Annexin V/propidium iodide staining coupled with flow cytometry indicated the induction of apoptosis in treated cells. Compound C1 induced apoptosis in MCF-7 cells and was mediated through the intrinsic pathway with a reduction in mitochondrial membrane potential and mitochondrial cytochrome c release to cytosol. Complex C1 activated caspase 9 as a result of cytochrome c release. Subsequently, western blot and real time PCR revealed a significant increase in Bax and Bad expression and a significant decrease in the expression levels of Bcl2 and HSP70. Furthermore, a flow cytometric analysis showed that treatment with compound C1 caused a significant arrest of MCF-7 cells in G0/G1 phase. The inhibitory analysis of compound C1 against derived MCF-7 stem cells showed a significant reduction in the aldehyde dehydrogenase-positive cell population and a significant reduction in the population of MCF-7 cancer stem cells in primary, secondary, and tertiary mammospheres. Moreover, treatment with C1 down-regulated the Wnt/ß-catenin self-renewal pathway. These findings indicate that complex C1 is a suppressive agent of MCF-7 cells that functions through the induction of apoptosis, cell cycle arrest, and the targeting of MCF-7-derived cancer stem cells. This work may lead to a better treatment strategy for the reduction of breast cancer recurrence.

A Zinc Morpholine Complex Prevents HCl/Ethanol-Induced Gastric Ulcers in a Rat Model.

Zinc is a naturally occurring element with roles in wound healing and rescuing tissue integrity, particularly in the gastrointestinal system, where it can be detected in the mucosal and submucosal layers. Zinc chelates are known to have beneficial effects on the gastrointestinal mucosa and in cases of gastric ulcer. We synthesized complexes of zinc featuring a heterocyclic amine binding amino acids then investigated their ability to enhance the gastric self-repair. Zinc-morpholine complex, Zn(L)SCN, namely showed strong free-radical scavenging, promotion of the DNA and RNA polymerases reconstruction and suppression of cell damage. The complex's mode of action is proposed to involve hydrogen bond formation via its bis(thiocyanato-k)zinc moiety. Zn(L)SCN complex had potent effects on gastric enzymatic activity both in vitro and in vivo. The complex disrupted the ulcerative process as demonstrated by changes in the intermediate metabolites of the oxidative pathway - specifically, reduction in the MDA levels and elevation of reduced glutathione together with an attenuation of oxidative DNA damage. Additionally, Zn(L)SCN restored the gastric mucosa, inhibited the production of pro-inflammatory cytokines (IL-6, TNF and the caspases), and preserved the gastric mucous balance. Zn(L)SCN thus exhibited anti-oxidative, anti-inflammatory and anti-apoptotic activities, all of which have cytoprotective effects on the gastric lining.

Pulchrin A, a New Natural Coumarin Derivative of Enicosanthellum pulchrum, Induces Apoptosis in Ovarian Cancer Cells via Intrinsic Pathway.

Drug resistance presents a challenge in chemotherapy and has attracted research interest worldwide and particular attention has been given to natural compounds to overcome this difficulty. Pulchrin A, a new compound isolated from natural products has demonstrated novel potential for development as a drug. The identification of pulchrin A was conducted using several spectroscopic techniques such as nuclear magnetic resonance, liquid chromatography mass spectrometer, infrared and ultraviolet spectrometry. The cytotoxicity effects on CAOV-3 cells indicates that pulchrin A is more active than cisplatin, which has an IC50 of 22.3 µM. Significant changes in cell morphology were present, such as cell membrane blebbing and formation of apoptotic bodies. The involvement of phosphatidylserine (PS) in apoptosis was confirmed by Annexin V-FITC after a 24 h treatment. Apoptosis was activated through the intrinsic pathway by activation of procaspases 3 and 9 as well as cleaved caspases 3 and 9 and ended at the executioner pathway, with the occurrence of DNA laddering. Apoptosis was further confirmed via gene and protein expression levels, in which Bcl-2 protein was down-regulated and Bax protein was up-regulated. Furthermore, the CAOV-3 cell cycle was disrupted at the G0/G1 phase, leading to apoptosis. Molecular modeling of Bcl-2 proteins demonstrated a high- binding affinity, which inhibited the function of Bcl-2 proteins and led to cell death. Results of the current study can shed light on the development of new therapeutic agents, particularly, human ovarian cancer treatments.

Acute Toxicity and Gastroprotection Studies of a New Schiff Base Derived Manganese (II) Complex against HCl/Ethanol-Induced Gastric Ulcerations in Rats.

Manganese is a crucial element for health. In this study, the gastroprotective efficacy of Mn (II) complex (MDLA) against acidified ethanol (HCl/Ethanol)-induced gastric ulceration in rats was evaluated. The animals were distributed into 5 groups. Groups 1 and 2 received carboxymethylcellulose (CMC), group 3 was pretreated with omeprazole, and groups 4 and 5 were given 10 and 20 mg/kg of MDLA, respectively. After one hour, CMC and HCl/Ethanol were given to groups 2-5 whilst the animals in group 1 were ingested with CMC. After sacrifice, gastric lesions were evaluated by wall mucus, gross appearance, histology, antioxidant enzymes and immunohistochemistry. Group 2 displayed severe gastric damage with a significant reduction in wall mucus. Conversely, gastric lesions were reduced in groups 3-5 by 85.72%, 56.51% and 65.93%, respectively. The rats in groups 3-5 showed up-regulation of heat shock protein 70 (Hsp70) with down-regulation of Bcl-2-associated protein x (Bax). Pretreatment with omeprazole or MDLA led to an increase in the uptake of Periodic Acid Schiff (PAS) stain in the glandular part of the gastric tissue, raised levels of prostaglandin E2 (PGE2) and superoxide dismutase (SOD), and a reduction in malondialdehyde (MDA) concentrations. These results suggested the gastroprotective action of Mn (II) complex.

Artonin E Induces Apoptosis via Mitochondrial Dysregulation in SKOV-3 Ovarian Cancer Cells.

Artonin E is a prenylated flavonoid isolated from the stem bark of Artocarpus elasticus Reinw.(Moraceae). This study aimed to investigate the apoptotic mechanisms induced by artonin E in a metastatic human ovarian cancer cell line SKOV-3 in vitro. MTT assay, clonogenic assay, acridine orange and propidium iodide double staining, cell cycle and annexin V analyses were performed to explore the mode of artonin E-induced cell death at different time points. DNA laddering, activation of caspases-3, -8, and -9, multi-parametric cytotoxicity-3 analysis by high-content screening, measurement of reactive oxygen species generation, and Western blot were employed to study the pathways involved in the apoptosis. MTT results showed that artonin E inhibited the growth of SKOV-3 cells, with IC50 values of 6.5±0.5 µg/mL after 72 h treatment, and showed less toxicity toward a normal human ovarian cell line T1074, with IC50 value of 32.5±0.5 µg/mL. Results showed that artonin E induced apoptosis and cell cycle arrest at the S phase. This compound also promoted the activation of caspases-3, -8, and -9. Further investigation into the depletion of mitochondrial membrane potential and release of cytochrome c revealed that artonin E treatment induced apoptosis via regulation of the expression of pro-survival and pro-apoptotic Bcl-2 family members. The expression levels of survivin and HSP70 proteins were also down regulated in SKOV-3 cells treated with artonin E. We propose that artonin E induced an antiproliferative effect that led to S phase cell cycle arrest and apoptosis through dysregulation of mitochondrial pathways, particularly the pro- and anti-apoptosis signaling pathways.