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Pyranocycloartobiloxanthone A, a novel gastroprotective compound from Artocarpus obtusus Jarret, against ethanol-induced acute gastric ulcer in vivo

Sidahmed HM, Hashim NM, Amir J, Abdulla MA, Hadi AH, Abdelwahab SI, et al.

Phytomedicine, 2013 Jul 15;20(10):834-43.
PMID: 23570997 DOI: 10.1016/j.phymed.2013.03.002

Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia. In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats. The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol. The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo. The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro. The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions. PA pretreatment significantly (p<0.05) restored the depleted GSH, NP-SH and NO levels in the gastric homogenate. Moreover, PA significantly (p<0.05) reduced the elevated MDA level due to ethanol administration. The gastroprotective effect of PA was associated with an over expression of HSP70 and suppression of Bax proteins in the ulcerated tissue. In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition. It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium. The efficacy of PA was accomplished safely without the presence of any toxicological parameters. The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori.

Matched MeSH terms: Artocarpus/chemistry*
Fulltext Antioxidant, antimicrobial and tyrosinase inhibitory activities of xanthones isolated from Artocarpus obtusus F.M. Jarrett

Hashim NM, Rahmani M, Ee GC, Sukari MA, Yahayu M, Amin MA, et al.

Molecules, 2012;17(5):6071-82.
PMID: 22614861 DOI: 10.3390/molecules17056071

One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical scavenger towards DPPH free radicals with IC50 value of 2 µg/mL with prominent discoloration observed in comparison with standard ascorbic acid, α-tocopherol and quercetin, The compound also exhibited antibacterial activity against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus subtilis (clinically isolated) with inhibition zone of 20 and 12 mm, respectively. However the other two xanthones were found to be inactive. For the tyrosinase inhibitory activity, again compound (1) displayed strong activity comparable with the standard kojic acid.

Matched MeSH terms: Artocarpus/chemistry*
Two new xanthones from Artocarpus obtusus

Hashim N, Rahmani M, Sukari MA, Ali AM, Alitheen NB, Go R, et al.

J Asian Nat Prod Res, 2010 Feb;12(2):106-12.
PMID: 20390751 DOI: 10.1080/10286020903450411

Two new xanthones, pyranocycloartobiloxanthone A (1) and dihydroartoindonesianin C (2), were isolated from the stem bark of Artocarpus obtusus Jarrett by chromatographic separation. Their structures were determined by using spectroscopic methods and comparison with known related compounds. Pyranocycloartobiloxanthone A (1) showed strong free radical scavenging activity by using DPPH assay as well as cytotoxicity towards K562, HL-60, and MCF7 cell lines.

Matched MeSH terms: Artocarpus/chemistry*
A new prenylated dihydrochalcone from the leaves of Artocarpus lowii

Jamil S, Sirat HM, Jantan I, Aimi N, Kitajima M

J Nat Med, 2008 Jul;62(3):321-4.
PMID: 18404311 DOI: 10.1007/s11418-008-0226-3

A new prenylated dihydrochalcone, 2',4'-dihydroxy-4-methoxy-3'-prenyldihydrochalcone (1), along with two known compounds, 2',4',4-trihydroxy-3'-prenylchalcone (2) and 2',4-dihydroxy-3',4'-(2,2-dimethylchromene)chalcone (3) were isolated from the leaves of Artocarpus lowii. The structures of 1-3 were elucidated by spectroscopic methods and by comparison with data reported in the literature. Compounds 1-3 showed strong free radical scavenging activity towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) measured by electron spin resonance (ESR) spectrometry.

Matched MeSH terms: Artocarpus/chemistry*
Flavonoids from the Bark of Artocarpus integer var. silvestris and their Anti-inflammatory Properties

Shaha MKK, Sirata HM, Jamil S, Jalil J

Nat Prod Commun, 2016 Sep;11(9):1275-1278.
PMID: 30807020

A new pyranoflavone, methoxycyclocommunol (1) together with four known flavonoids, artonin F (2), heteroflavanone A (3), cudraflavone C (4) and cyclocommunol (5) were isolated from the bark of Artocarpus integer var. silvestris Corner. Their structures were elucidated through extensive spectroscopic- techniques (UV, IR, MS, 1D-NMR and 2D-NMR) and by comparison with literature data. All the pure compounds were tested for their anti-inflammatory activities by using screening kit and radioimmunoassay methods. In a 15-lipoxygenase (15-LOX) inhibitory assay, compounds 1, 2, 4 and 5 gave weak percentages of inhibition, 16.5, 18.3, 17.6, 10.2%, respectively at the concentration of 100 μM. Compounds 1, 3 and 4, however, showed strong dose- dependent inhibition towards prostaglandin E₂ (PGE₂) production in lipopolysaccharide-induced human whole blood using a radioimmunoassay method with IC₅₀ values of 4.3, 0.8, and 0.07 μM, respectively suggesting that they strongly exhibited cyclooxygenase-2 (COX-2) activity.

Matched MeSH terms: Artocarpus/chemistry*
Flavonoids of Artocarpus heterophyllus Lam. heartwood inhibit the innate immune responses of human phagocytes

Septama AW, Jantan I, Panichayupakaranant P

J Pharm Pharmacol, 2018 Sep;70(9):1242-1252.
PMID: 29943393 DOI: 10.1111/jphp.12952

OBJECTIVES: To investigate the effects of flavonoids isolated from Artocarpus heterophyllus. heartwood on chemotaxis, phagocytosis, reactive oxygen species (ROS) production and myeloperoxidase (MPO) activity of human phagocytes.
METHODS: Chemotaxis was evaluated using a modified Boyden chamber and phagocytosis was determined by flowcytometer. Respiratory burst was investigated by luminol-based chemiluminescence assay while MPO activity was determined by colorimetric assay.
KEY FINDINGS: Artocarpanone and artocarpin strongly inhibited all steps of phagocytosis. Artocarpanone and artocarpin showed strong chemotactic activity with IC50 values of 6.96 and 6.10 μm, respectively, which were lower than that of ibuprofen (7.37 μm). Artocarpanone was the most potent compound in inhibiting ROS production of polymorphonuclear leucocytes and monocytes with IC50 values comparable to those of aspirin. Artocarpin at 100 μg/ml inhibited phagocytosis of opsonized bacteria (28.3%). It also strongly inhibited MPO release with an IC50 value (23.3 μm) lower than that of indomethacin (69 μm). Structure-activity analysis indicated that the number of hydroxyl group, the presence of prenyl group and variation of C-2 and C-3 bonds might contribute towards their phagocytosis.
CONCLUSIONS: Artocarpanone and artocarpin were able to suppress strongly the phagocytosis of human phagocytes at different steps and have potential to be developed into potent anti-inflammatory agents.

Matched MeSH terms: Artocarpus*
Fulltext The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells

Etti IC, Abdullah R, Kadir A, Hashim NM, Yeap SK, Imam MU, et al.

PLoS One, 2017;12(8):e0182357.
PMID: 28771532 DOI: 10.1371/journal.pone.0182357

Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.

Matched MeSH terms: Artocarpus/metabolism; Artocarpus/chemistry
Chryseobacterium artocarpi sp. nov., isolated from the rhizosphere soil of Artocarpus integer

Venil CK, Nordin N, Zakaria ZA, Ahmad WA

Int J Syst Evol Microbiol, 2014 Sep;64(Pt 9):3153-9.
PMID: 24958763 DOI: 10.1099/ijs.0.063594-0

A bacterial strain, designated UTM-3(T), isolated from the rhizosphere soil of Artocarpus integer (cempedak) in Malaysia was studied to determine its taxonomic position. Cells were Gram-stain-negative, non-spore-forming rods, devoid of flagella and gliding motility, that formed yellow-pigmented colonies on nutrient agar and contained MK-6 as the predominant menaquinone. Comparative analysis of the 16S rRNA gene sequence of strain UTM-3(T) with those of the most closely related species showed that the strain constituted a distinct phyletic line within the genus Chryseobacterium with the highest sequence similarities to Chryseobacterium lactis NCTC 11390(T), Chryseobacterium viscerum 687B-08(T), Chryseobacterium tructae 1084-08(T), Chryseobacterium arthrosphaerae CC-VM-7(T), Chryseobacterium oncorhynchi 701B-08(T), Chryseobacterium vietnamense GIMN1.005(T), Chryseobacterium bernardetii NCTC 13530(T), Chryseobacterium nakagawai NCTC 13529(T), Chryseobacterium gallinarum LMG 27808(T), Chryseobacterium culicis R4-1A(T), Chryseobacterium flavum CW-E2(T), Chryseobacterium aquifrigidense CW9(T), Chryseobacterium ureilyticum CCUG 52546(T), Chryseobacterium indologenes NBRC 14944(T), Chryseobacterium gleum CCUG 14555(T), Chryseobacterium jejuense JS17-8(T), Chryseobacterium oranimense H8(T) and Chryseobacterium joostei LMG 18212(T). The major whole-cell fatty acids were iso-C15 : 0 and iso-C17 : 1ω9c, followed by summed feature 4 (iso-C15 : 0 2-OH and/or C16 : 1ω7t) and iso-C17 : 0 3-OH, and the polar lipid profile consisted of phosphatidylethanolamine and several unknown lipids. The DNA G+C content strain UTM-3(T) was 34.8 mol%. On the basis of the phenotypic and phylogenetic evidence, it is concluded that the isolate represents a novel species of the genus Chryseobacterium, for which the name Chryseobacterium artocarpi sp. nov. is proposed. The type strain is UTM-3(T) ( = CECT 8497(T) = KCTC 32509(T)).

Matched MeSH terms: Artocarpus/microbiology*
Fulltext Artocarpus altilis extracts as a food-borne pathogen and oxidation inhibitors: RSM, COSMO RS, and molecular docking approaches

Ahmad MN, Karim NU, Normaya E, Mat Piah B, Iqbal A, Ku Bulat KH

Sci Rep, 2020 06 12;10(1):9566.
PMID: 32533034 DOI: 10.1038/s41598-020-66488-7

Lipid oxidation and microbial contamination are the major factors contributing to food deterioration. Food additives like antioxidants and antibacterials can prevent food spoilage by delaying oxidation and preventing the growth of bacteria. Artocarpus altilis leaves exhibited biological properties that suggested its use as a new source of natural antioxidant and antimicrobial. Supercritical fluid extraction (SFE) was used to optimize the extraction of bioactive compounds from the leaves using response surface methodology (yield and antioxidant activity). The optimum SFE conditions were 50.5 °C temperature, 3784 psi pressure and 52 min extraction time. Verification test results (Tukey's test) showed that no significant difference between the expected and experimental DPPH activity and yield value (99%) were found. Gas-chromatography -mass spectrometry (GC-MS) analysis revealed three major bioactive compounds existed in A. altilis extract. The extract demonstrated antioxidant and antibacterial properties with 2,3-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, ferric reducing ability of plasma (FRAP), hydroxyl radical scavenging activity, tyrosinase mushrrom inhibition of 41.5%, 8.15 ± 1.31 (µg of ascorbic acid equivalents), 32%, 37% and inhibition zone diameter of 0.766 ± 0.06 cm (B. cereus) and 1.27 ± 0.12 cm (E. coli). Conductor like screening model for real solvents (COSMO RS) was performed to explain the extraction mechanism of the major bioactive compounds during SFE. Molecular electrostatic potential (MEP) shows the probability site of nucleophilic and electrophilic attack during bacterial inhibition. Based on molecular docking study, non-covalent interactions are the main interaction occurring between the major bioactive compounds and bacteria (antibacterial inhibition).

Matched MeSH terms: Artocarpus/chemistry*
Fulltext Pollination implications of the diverse diet of tropical nectar-feeding bats roosting in an urban cave

Lim VC, Ramli R, Bhassu S, Wilson JJ

PeerJ, 2018;6:e4572.
PMID: 29607265 DOI: 10.7717/peerj.4572

Background: Intense landscaping often alters the plant composition in urban areas. Knowing which plant species that pollinators are visiting in urban areas is necessary for understanding how landscaping impacts biodiversity and associated ecosystem services. The cave nectar bat,Eonycteris spelaea, is an important pollinator for many plants and is often recorded in human-dominated habitats. Previous studies of the diet ofE. spelaearelied on morphological identification of pollen grains found in faeces and on the body of bats and by necessity disregarded other forms of digested plant material present in the faeces (i.e., plant juice and remnants). The main objective of this study was to examine the diet of the nectarivorous bat,E. spelaea,roosting in an urban cave at Batu Caves, Peninsular Malaysia by identifying the plant material present in the faeces of bats using DNA metabarcoding.
Methods: Faeces were collected under the roost ofE. spelaeaonce a week from December 2015 to March 2016. Plant DNA was extracted from the faeces, Polymerase chain reaction (PCR) amplified atITS2andrbcLregions and mass sequenced. The resultant plant operational taxonomic units were searched against NCBI GenBank for identification.
Results: A total of 55 species of plants were detected from faeces ofE. spelaeaincludingArtocarpus heterophyllus, Duabanga grandifloraandMusaspp. which are likely to be important food resources for the cave nectar bat.
Discussion: Many native plant species that had not been reported in previous dietary studies ofE. spelaeawere detected in this study includingBauhinia strychnoideaandUrophyllum leucophlaeum, suggesting thatE. spelaearemains a crucial pollinator for these plants even in highly disturbed habitats. The detection of many introduced plant species in the bat faeces indicates thatE. spelaeaare exploiting them, particularlyXanthostemon chrysanthus,as food resources in urban area. Commercial food crops were detected from all of the faecal samples, suggesting thatE. spelaeafeed predominantly on the crops particularly jackfruit and banana and play a significant role in pollination of economically important plants. Ferns and figs were also detected in the faeces ofE. spelaeasuggesting future research avenues to determine whether the 'specialised nectarivorous'E. spelaeafeed opportunistically on other parts of plants.

Matched MeSH terms: Artocarpus
Involvement of NF-κB and Bcl2/Bax signaling pathways in the apoptosis of MCF7 cells induced by a xanthone compound Pyranocycloartobiloxanthone A

Mohan S, Abdelwahab SI, Kamalidehghan B, Syam S, May KS, Harmal NS, et al.

Phytomedicine, 2012 Aug 15;19(11):1007-15.
PMID: 22739412 DOI: 10.1016/j.phymed.2012.05.012

The plant Artocarpus obtusus is a tropical plant that belongs to the family Moraceae. In the present study a xanthone compound Pyranocycloartobiloxanthone A (PA) was isolated from this plant and the apoptosis mechanism was investigated. PA induced cytotoxicity was observed using MTT assay. High content screening (HCS) was used to observe the nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and cytochrome c release. Reactive oxygen species formation was investigated on treated cells by using fluorescent analysis. Human apoptosis proteome profiler assays were performed to investigate the mechanism of cell death. In addition mRNA levels of Bax and Bcl2 were also checked using RT-PCR. Caspase 3/7, 8 and 9 were measured for their induction while treatment. The involvement of NF-κB was analyzed using HCS assay. The results showed that PA possesses the characteristics of selectively inducing cell death of tumor cells as no inhibition was observed in non-tumorigenic cells even at 30 μg/ml. Treatment of MCF7 cells with PA induced apoptosis with cell death-transducing signals, that regulate the MMP by down-regulation of Bcl2 and up-regulation of Bax, triggering the cytochrome c release from mitochondria to cytosol. The release of cytochrome c triggered the activation of caspases-9, then activates downstream executioner caspase-3/7 and consequently cleaved specific substrates leading to apoptotic changes. This form of apoptosis was found closely associated with the extrinsic pathway caspase (caspase-8) and inhibition of translocation of NF-κB from cytoplasm to nucleus. The results demonstrated that PA induced apoptosis of MCF7 cells through NF-κB and Bcl2/Bax signaling pathways with the involvement of caspases.

Matched MeSH terms: Artocarpus/chemistry*
Fulltext Assessment of antioxidant capacity and cytotoxicity of selected Malaysian plants

Ling LT, Radhakrishnan AK, Subramaniam T, Cheng HM, Palanisamy UD

Molecules, 2010 Apr;15(4):2139-51.
PMID: 20428033 DOI: 10.3390/molecules15042139

Thirteen Malaysian plants; Artocarpus champeden, Azadirachta indica, Fragaria x ananassa, Garcinia mangostana, Lawsonia inermis, Mangifera indica, Nephelium lappaceum, Nephelium mutobile, Peltophorum pterocarpum, Psidium guajava and Syzygium aqueum, selected for their use in traditional medicine, were subjected to a variety of assays. Antioxidant capability, total phenolic content, elemental composition, as well as it cytotoxity to several cell lines of the aqueous and ethanolic extracts from different parts of these selected Malaysian plants were determined. In general, the ethanolic extracts were better free radical scavengers than the aqueous extracts and some of the tested extracts were even more potent than a commercial grape seed preparation. Similar results were seen in the lipid peroxidation inhibition studies. Our findings also showed a strong correlation of antioxidant activity with the total phenolic content. These extracts when tested for its heavy metals content, were found to be below permissible value for nutraceutical application. In addition, most of the extracts were found not cytotoxic to 3T3 and 4T1 cells at concentrations as high as 100 microg/mL. We conclude that although traditionally these plants are used in the aqueous form, its commercial preparation could be achieved using ethanol since a high total phenolic content and antioxidant activity is associated with this method of preparation.

Matched MeSH terms: Artocarpus/chemistry
Fulltext Antiproliferative activity of xanthones isolated from Artocarpus obtusus

Hashim NM, Rahmani M, Ee GC, Sukari MA, Yahayu M, Oktima W, et al.

J Biomed Biotechnol, 2012;2012:130627.
PMID: 21960741 DOI: 10.1155/2012/130627

An investigation of the chemical constituents in Artocarpus obtusus species led to the isolation of three new xanthones, pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2), and pyranocycloartobiloxanthone B (3). The compounds were subjected to antiproliferative assay against human promyelocytic leukemia (HL60), human chronic myeloid leukemia (K562), and human estrogen receptor (ER+) positive breast cancer (MCF7) cell lines. Pyranocycloartobiloxanthone A (1) consistently showed strong cytotoxic activity against the three cell lines compared to the other two with IC(50) values of 0.5, 2.0 and 5.0 μg/mL, respectively. Compound (1) was also observed to exert antiproliferative activity and apoptotic promoter towards HL60 and MCF7 cell lines at respective IC(50) values. The compound (1) was not toxic towards normal cell lines human nontumorigenic breast cell line (MCF10A) and human peripheral blood mononuclear cells (PBMCs) with IC(50) values of more than 30 μg/mL.

Matched MeSH terms: Artocarpus/chemistry*
Enhanced growth of lactobacilli in soymilk upon immobilization on agrowastes

Teh SS, Ahmad R, Wan-Abdullah WN, Liong MT

J Food Sci, 2010 Apr;75(3):M155-64.
PMID: 20492305 DOI: 10.1111/j.1750-3841.2010.01538.x

Cell immobilization is an alternative to microencapsulation for the maintenance of cells in a liquid medium. The objective of this study was to evaluate the effects of agrowastes from durian (Durio zibethinus), cempedak (Artocarpus champeden), and mangosteen (Garcinia mangostana) as immobilizers for lactobacilli grown in soymilk. Rinds from the agrowastes were separated from the skin, dried, and ground (150 microm) to form powders and used as immobilizers. Scanning electron microscopy revealed that lactobacilli cells were attached and bound to the surface of the immobilizers. Immobilized cells of Lactobacillus acidophilus FTDC 1331, L. acidophilus FTDC 2631, L. acidophilus FTDC 2333, L. acidophilus FTDC 1733, and L. bulgaricus FTCC 0411 were inoculated into soymilk, stored at room temperature (25 degrees C) and growth properties were evaluated over 168 h. Soymilk inoculated with nonimmobilized cells was used as the control. Utilization of substrates, concentrations of lactic and acetic acids, and changes in pH were evaluated in soymilk over 186 h. Immobilized lactobacilli showed significantly better growth (P < 0.05) compared to the control, accompanied by higher production of lactic and acetic acids in soymilk. Soymilk containing immobilized cells showed greater reduction of soy sugars such as stachyose, raffinose, sucrose, fructose, and glucose compared to the control (P < 0.05).

Matched MeSH terms: Artocarpus
Fulltext Artonin E Induces Apoptosis via Mitochondrial Dysregulation in SKOV-3 Ovarian Cancer Cells

Rahman MA, Ramli F, Karimian H, Dehghan F, Nordin N, Ali HM, et al.

PLoS One, 2016;11(3):e0151466.
PMID: 27019365 DOI: 10.1371/journal.pone.0151466

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.

Matched MeSH terms: Artocarpus/chemistry

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