Possible use of miRNAs-146a and -499 expression and their polymorphisms as diagnostic markers for rheumatoid arthritis

A novel polycyclic bridged-ring xanthene 2 was synthesized by nucleophilic substitution followed by Michael addition reaction between parent dibenzoxanthene 1 and acetylacetone. The structure of compound 2 was also confirmed by single-crystal X-ray diffraction. We studied the binding activity of this compound with bovine serum albumin (BSA) by fluorescent and UV–visible spectra. The results showed that compound had strong binding ability with BSA. Cell viability in five tumor cell lines was studied by MTT assay. The cytotoxic effect of bridged-ring xanthene 2 against BEL-7402 cells was examined by morphological analyses and biochemical assays. Significant nuclear damages of BEL-7402 cells were observed after cells were treated with compound in a comet assay. The compound also caused DNA damage and S phase arrest in BEL-7402 cells. The efficient induction of apoptosis by the compound was confirmed by flow cytometry. Additionally, the characteristic nuclear and morphological changes during apoptotic cell death were investigated by fluorescent microscopy. The compound 2 enhanced the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Western blot assay indicated that the compound can active caspase-3, caspase-7, down-regulate the level of Bcl-2, Bcl-x, and up-regulate the level of pro-apoptosis protein Bax. The compound 2 induces apoptosis of BEL-7402 cells through a ROS-mediated mitochondrial dysfunction pathway.     

The induction of apoptosis in SGC-7901 cells through the ROS-mediated mitochondrial dysfunction pathway by a Ir(III) complex

A new ligand BTCP and its iridium(III) complex [Ir(ppy)₂(BTCP)]PF₆ (Ir-1) were synthesized and characterized by elemental analysis, ESI–MS, IR, ¹H NMR and ¹³C NMR. The cytotoxic activity in vitro of the ligand and its complex against SGC-7901, HeLa, HOS, PC-12, BEL-7402, MG-63, SiHa, A549, HepG2 and normal cell LO2 were evaluated by MTT method [MTT = (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)]. The apoptosis was assayed with AO/EB and Hoechst 33258 staining methods. The reactive oxygen species (ROS), mitochondrial membrane potential, autophagy and cell invasion were studied under fluorescent microscope. The expression of caspases and Bcl-2 family proteins were investigated by western blot. The IC₅₀ values of complex toward SGC-7901, BEL-7402 and MG-63 cells are 3.9 ± 0.5, 5.4 ± 1.2 and 4.2 ± 0.6 µM. The complex can increase the levels of ROS, and induce a decrease in the mitochondrial membrane potential. Ir-1 inhibits the cell growth at G0/G1 phase in SGC-7901 cells, and the complex can induce both autophagy and apoptosis and inhibit the cell invasion. And the complex induces apoptosis through a ROS-mediated mitochondrial dysfunction pathway.     

Synthesis and antitumor activities of novel rhein α-aminophosphonates conjugates

Several rhein α-aminophosphonates conjugates (5a–5q) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially, compound 5i exhibited the strongest cytotoxicity against Hct-116 cells (IC₅₀ was 5.32 μM). All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The mechanism of compound 5i was preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound 5i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis showed that these compound 5i mainly arrested Hct-116 cells in G1 stage. The effects of 5i on the activation of caspases expression indicated that 5i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 5i to DNA were investigated by methods (UV–vis, fluorescence, CD spectroscopy and FRET-melting) in compare with that of rhein. Results indicated that 5i showed moderate ability to interact ct-DNA.     

Musca Domestica Larva Lectin Induces Apoptosis in BEL-7402 Cells Through a Ca2+/JNK-mediated Mitochondrial Pathway

Although Musca domestica larvae lectin (MLL) is able to inhibit cancer cell proliferation and to induce cancer cell apoptosis, the molecular mechanism(s) responsible for these processes remain elusive. In the current study, the signaling network underlying the MLL-induced apoptosis of human hepatoma BEL-7402 cell was investigated. Our data found out that MLL causes a sustained increase of the intracellular Ca²⁺ and this process was prevented by the intracellular calcium chelator, BAPTA-AM, suggesting the involvement of intracellular Ca²⁺ in MLL-induced cell apoptosis. MLL also causes the production of reactive oxygen species and elevates the phosphorylation status of JNK, processes associated with the increased cytoplasmic Ca²⁺. The mitochondrial permeability transition pore (MPTP) opening study showed that MLL treatment of BEL-7402 cells results in the opening of MPTP and a reduction of mitochondrial transmembrane potential. In such condition, cytochrome-c was detected to be released from mitochondria to cytoplasm through the MPTP. This eventually activates caspase-3 and thus results in apoptosis of the tested BEL-7402 cells. According to a comprehensive review of all the evidence, it is concluded that MLL induces apoptosis of BEL-7402 cells through a Ca²⁺/JNK-mediated MPTP pathway.     

基于肝癌细胞线粒体功能受损和caspase-3信号通路探讨罗哌卡因促进肝癌细胞凋亡的作用机制研究

摘要 目的：基于肝癌细胞线粒体功能受损和天冬氨酸蛋白水解酶3（caspase-3）信号通路探讨罗哌卡因促进肝癌细胞凋亡的作用机制。方法：选用细胞株人肝癌细胞BEL-7402进行实验研究。用不同浓度罗哌卡因处理BEL-7402细胞后,采用溴化噻唑蓝四氮唑（MTT）法检测肝癌细胞的增殖情况,光镜及4,6-二苯胺-2-苯吲哚二盐酸盐（DAPI）溶液染色观察细胞形态,台盼蓝染色法测定细胞活力,流式细胞术分析BEL-7402细胞的凋亡情况,电子显微镜下观察细胞线粒体,激光共聚焦显微镜观察caspase-3在BEL-7402细胞中的细胞核迁移情况,蛋白免疫印迹试验评价罗哌卡因对细胞质凋亡相关蛋白、线粒体凋亡相关蛋白、BEL-7402细胞和线粒体凋亡相关蛋白表达的影响。结果：罗哌卡因能够抑制肝癌细胞的生长,并呈剂量依赖性和时间依赖性。罗哌卡因可诱导BEL-7402细胞发生凋亡,显著增加BEL-7402细胞的凋亡率。罗哌卡因能够损伤肝癌细胞线粒体功能。激光共聚焦显微镜观察显示caspase-3分子迁移到细胞核。罗哌卡因与caspase-3相互作用,促进caspase-3向细胞核内迁移,刺激caspase-3和聚腺苷二磷酸核糖聚合酶（PARP-1）、天冬氨酸蛋白水解酶9（caspase-9）蛋白的表达,抑制B细胞淋巴瘤-2基因（Bcl-2）的表达,促进凋亡酶激活因子（Apaf-1）的表达,促进线粒体释放细胞色素C（Cytochrome C）,激活caspase-3活性。结论：罗哌卡因具有促进肝癌细胞凋亡的作用,其作用机制可能与破坏肝癌细胞线粒体功能和激活caspase-3信号通路有关。     

Synthesis and antitumor activities of novel dipeptide derivatives derived from dehydroabietic acid

A series of dipeptide derivatives from dehydroabietic acid were designed and synthesized as novel antitumor agents. The antitumor activities screening indicated that many compounds showed moderate to high levels of inhibition activities against NCI-H460, HepG2, SK-OV-3, BEL-7404, HeLa and HCT-116 cancer cell lines and that some displayed more potent inhibitory activities than commercial anticancer drug 5-fluorouracil. The mechanism of representative compound 7b was studied by AO/EB staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which exhibited that the compound could induce apoptosis in HeLa cells. Further investigation showed that compound 7b induced apoptosis of HeLa cells through a mitochondrial pathway.     

Tyroserleutide tripeptide affects calcium homeostasis of human hepatocarcinoma BEL-7402 cells

This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism preliminarily. YSL, at doses of 80 μg-kg^-1 · d^-1, 160 μg·kg^-1 ·d^-1 and 320 μg · kg^-1 · d^-1 significantly inhibited the growth of the human hepatocarcinoma BEL-7402 tumor in nude mice, producing inhibition of 21.66%, 41.34%, and 34.78%, respectively. Ultra structure of BEL-7402 tumor in nude mice showed that YSL could induce tumor cells apoptosis and necrosis, cell organelle mitochondria and endoplasmic reticulum damage, and calcium overload. By confocal laser scanning microscopy and flow cytometry, we found that 10 μg/mL YSL rapidly induced an increase of the concentration of cytoplasmic free calcium in BEL-7402 cells in vitro, and maintained high concentrations of cytoplasmic free calcium for 1 h. Then the calcium concentration began to decrease after 2 h, and was lower than that of the control group at 4 h and 24 h (P< 0.05). YSL also decreased the mitochondrial transmembrane potential of BEL-7402 cells in vitro, but had no effect on the calcium homeostasis or mitochondrial transmembrane potential of Chang liver hepatocytes. So affecting calcium homeostasis, then inducing apoptosis and necrosis may be a mechanism by which YSL inhibits the tumor growth in animal model.     

Tyroserleutide tripeptide affects calcium homeostasis of human hepatocarcinoma BEL-7402 cells

Copyright by Science in China Press 2005 Primary hepatocarcinoma is one of the most fre-quent digestive-tract cancers, particularly in China. The incidence and death rate of primary hepatocarci-noma in China is the highest in the world, with about 1100 thousands people dying from primary hepatocar-cinoma per year[1]. Although the chemotherapeutic agents are the main therapeutic approach for hepato- carcinoma, they are relatively ineffective and result in many toxic and side effects. Accordin…     

PPARγ mediates the effects of WIN55,212-2, an synthetic cannabinoid, on the proliferation and apoptosis of the BEL-7402 hepatocarcinoma cells

Cannabis sativa has long been used as a traditional medicine in China. Among its effective compounds are cannabinoids. This study determined the effect of WIN55,212-2 (WIN), a synthetic cannabinoid, on the BEL-7402 human hepatocellular carcinoma (HCC) cell line. The results showed that WIN could decrease the proliferation of BEL-7402 cells. Moreover, WIN could cause apoptosis of the cells via up-regulation of Bax expression, down-regulation of Bcl-2 expression, induction of the mitochondrial membrane potential, increase of caspase-3, -8 and -9 activities, and induction of the cleavage of caspase-3 and poly-ADP-ribose polymerase (PARP). The WIN-induced apoptosis was accompanied by the up-regulation of PPARγ expression, the activation of PPARγ DNA binding activity, and a down-regulation of PPARγ target oncogene c-myc. Conversely, the effects of WIN could be attenuated by PPARγ antagonist GW9662, and the WIN induced PPARγ expression was partially attenuated by AM630, a cannabinoid receptor-2 antagonist, whereas the WIN-induced reduction of c-myc expression was partially restored by GW9662. Collectively, our results suggest that WIN can decrease the proliferation and cause apoptosis of the BEL-7402 cells via a mitochondrial-caspase pathway and mediated by PPARγ. These results may provide a basis for the application of WIN in HCC treatment.     

PER1对人肝癌细胞BEL-7402辐射敏感性的影响

本文通过X射线照射SMMC-7721、BEL-7402和HepG2三种肝癌细胞后,以克隆形成试验检测其存活分数,结果显示在梯度剂量X射线0、2、4、6、8、10 Gy照射下SMMC-7721、BEL-7402、HepG2三种细胞克隆存活分数逐渐下降,其中SMMC-7721在三种肝癌细胞系中对辐射最敏感,BEL-7402辐射抗性在三种肝癌细胞系中最高。Western blot检测发现PER1在SMMC-7721中的表达水平明显显著高于BEL-7402和HepG2(P<0.05)。过表达PER1蛋白以后,BEL-7402接受5 Gy X射线照射后凋亡明显增多,同时,western blot和RT-qPCR试验结果发现,X射线照射过表达PER1的BEL-7402细胞,抗凋亡蛋白Bcl-2表达明显降低,凋亡执行蛋白Caspase-3断裂明显增多。研究结果表明PER1蛋白的高水平表达可以促进X射线诱导的凋亡,增强肝癌细胞的辐射敏感性。     

In vitro cytotoxicity of novel 2,5,7-tricarbo-substituted indoles derived from 2-amino-5-bromo-3-iodoacetophenone

A series of novel 2,5,7-tricarbo-substituted indoles were prepared via sequential Sonogashira and Suzuki–Miyaura cross-coupling of 2-amino-5-bromo-3-iodoacetophenone with terminal acetylenes and aryl/styrylboronic acids followed by palladium chloride-mediated heteroannulation of the incipient 5-aryl/styryl-substituted 2-amino-3-(arylalkynyl)acetophenones. These polycarbo-substituted indole derivatives were evaluated for potential in vitro antiproliferative activity against the human breast adenocarcinoma (MCF-7) and human cervical cancer (HeLa) cell lines. Compounds 6f, 6i, 6k, 6m and 6n were found to exhibit significant cytotoxicity and selectivity against the HeLa cells. Compounds 6i and 6m were chosen as representative examples to evaluate their pro-apoptotic efficacy against the HeLa cell line. The compounds induced apoptosis through cell membrane alteration and DNA fragmentation caspase-dependent pathways.     

New quinoline/chalcone hybrids as anti-cancer agents: Design,synthesis, and evaluations of cytotoxicity and PI3K inhibitory activity

A series of quinoline-chalcone hybrids was designed as potential anti-cancer agents, synthesized and evaluated. Different cytotoxic assays revealed that compounds experienced promising activity. Compounds 9i and 9j were the most potent against all the cell lines tested with IC₅₀ = 1.91–5.29 µM against A549 and K-562 cells. Mechanistically, 9i and 9j induced G₂/M cell cycle arrest and apoptosis in both A549 and K562 cells. Moreover, all PI3K isoforms were inhibited non selectively with IC₅₀s of 52–473 nM when tested against the two mentioned compounds with 9i being most potent against PI3K-γ (IC₅₀ = 52 nM). Docking of 9i and 9j showed a possible formation of H-bonding with essential valine residues in the active site of PI3K-γ isoform. Meanwhile, Western blotting analysis revealed that 9i and 9j inhibited the phosphorylation of PI3K, Akt, mTOR, as well as GSK-3β in both A549 and K562 cells, suggesting the correlation of blocking PI3K/Akt/mTOR pathway with the above antitumor activities. Together, our findings support the antitumor potential of quinoline-chalcone derivatives for NSCLC and CML by inhibiting the PI3K/Akt/mTOR pathway.     

Cytotoxicity of compounds from Xylopia aethiopica towards multi-factorial drug-resistant cancer cells

IntroductionMultidrug resistance (MDR) in cancer represent a major hurdle in chemotherapy. Previously, the methanol extract of the medicinal spice Xylopia aethiopica displayed considerable cytotoxicity against multidrug resistant (MDR) cancer cell lines.MethodsThe present study was designed to assess the cytotoxicity of compounds, 16α-hydroxy-ent-kauran-19-oic acid (2), 3,4′,5-trihydroxy-6″,6″-dimethylpyrano[2,3-g]flavone (3), isotetrandrine (5) and trans-tiliroside (6) derived from the methanol crude extract of Xylopia aethiopica against 9 drug-sensitive and -resistant cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analyzed via flow cytometry.ResultsFlavonoid 3 and alkaloid 5 also displayed IC₅₀ values ranging from 2.61 µM (towards leukemia CCRF-CEM cells) to 18.60 µM (towards gliobastoma multiforme U87MG.ΔEGFR cells) and from 1.45 µM (towards HepG2 cells) to 7.28 µM (towards MDA-MB-231-pcDNA cells), respectively. IC₅₀ values ranged from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. Compound 3 induced apoptosis in leukemia CCRF-CEM cells mediated by the disruption of the MMP, whilst 5 induced apoptosis mediated by ROS production.ConclusionsCompounds 2 and 5 represent potential cytotoxic phytochemicals that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug-resistant cancers.     

Synthesis and evaluation of 3-salicyloylpyridine derivatives as cytotoxic mitochondrial apoptosis inducers

A series of novel 3-salicyloylpyridines (4a–h) were synthesized with good yield by modified Knoevenagel–Stobbel method; o-allylation with allyl bromide lead to formation of compounds (5a–h). The synthesized compounds were characterized by spectroscopic techniques and evaluated for cytotoxic activity against human cancer cell lines. Compounds bearing hydroxyl group displayed high cytotoxicity (4a–h) as compared to o-allylated molecules (5a–h). The most active compound 4b was selected for further investigation to look for mechanism of cell death in prostate cancer (PC-3) cells. The apoptotic bodies induced by 4b in PC-3 cells were scanned by confocal microscopy and confirmed by scanning electron microscopy (SEM). Further results obtained from spectrofluorimetric determination of mitochondrial membrane potential (ΔΨm) and intracellular reactive oxygen species (ROS) in treated PC-3 cells revealed that mitochondria dependent apoptosis was involved in the cell death.     

IL—6诱导肝癌细胞BEL—7402细胞凋亡及其Ca^2＋转导机制

白细胞介素－6（interleukin-6,IL-6）具有直接或间接的抗肿瘤活性,本组在以前的体内外实验中证明其具有明显的抑制肝癌作用。本文主要报告应用流式细胞仪和共聚焦显微镜检测IL－6对肝癌细胞（BEL－7402）凋亡的作用和该过程中Ca^2 转导机制。生长曲线描绘以及MTT分析结果表明,IL－6（6000u/ml）作用于BEL－7402细胞24小时后,生长抑制率达12％左右,而流式细胞仪结果显示IL－60（6000u/ml）作用于BEL－7402细胞24小时后,BEL－7402细胞凋亡率达8.2％。流式细胞仪分析还表明,IL－60（6000u/ml）作用于BEL－7402细胞24小时后,对照组平均FTTC荧光值为1.03而IL－60（6000u/ml）组为0.759,也就是说,IL－6引起了bcl－2基因表达下降。激光共聚焦显微镜测定表明,IL－60（6000u/ml）作用于BEL－7402细胞后,胞浆[Ca^2 ]c升高达2倍。若事先加入TC（thapsigargin),15min后再加入IL－6,则抑制了胞浆内[Ca^2 ]c升高;事先10min或5min分别加入EGTA和普鲁卡因（procaine）也有同样的抑制作用。上述结果表明,IL－6在一定剂量下可以诱导肝癌细胞BEL－7402发生细胞凋亡,该凋亡过程可能与Ca^2 转导及bcl-2基因表达下调有关。     

Dual-targeting antitumor conjugates derived from platinum(IV) prodrugs and microtubule inhibitor CA-4 significantly exhibited potent ability to overcome cisplatin resistance

Here we report that three platinum(IV) prodrugs containing a tubulin inhibitor CA-4, as dual-targeting platinum(IV) prodrug, were synthesized and evaluated for antitumor activity using MTT assay. Among them, complex 9 exhibited the most potent antitumor activity against the tested cancer lines including cisplatin resistance cancer cells, and simultaneously displayed lower toxicity compared to cisplatin, respectively. Moreover, complex 9, in which was conjugated to an inhibitor of tubulin at one axial position of platinum(IV) complex, could effectively enter the cancer cells, and significantly induce cell apoptosis and arrest the cell cycle in A549 cells at G2/M stage, and dramatically disrupt the microtubule organization. In addition, mechanism studies suggested that complex 9 significantly induced reactive oxygen species (ROS) generation and decreased mitochondrial trans-membrane potential (MMP) in A549 cells, and effectively induced activation of caspases triggering apoptotic signaling through mitochondrial dependent apoptosis pathways.     

Synthesis and characterisation of (Z)-styrylbenzene derivatives as potential selective anticancer agents

To identify anticancer agents with high potency and low toxicity, a series of (Z)-styrylbenzene derivatives were synthesised and evaluated for anticancer activities using a panel of nine cancer cell lines and two noncancerous cell lines. Most derivatives exhibited significant anti-proliferative activities against five cancer cell lines, including MGC-803 and BEL-7402. (Z)-3-(p-Tolyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (6h) showed a strong inhibitory effect on MGC-803 cells (IC₅₀?50?50 value of 6h in L-02 cells was 10,000-fold higher than in MGC-803 cells. Compound 6h inhibited proliferation of BEL-7402 cells by arresting at the G2/M phase through up-regulation of cyclin B1 expression, down-regulation of cyclin A and D1 expression, and induction of apoptosis. In addition, 6h inhibited the migration of BEL-7402 cells and the formation of cell colonies.     

Multisubstituted indole–acrylonitrile hybrids as potential cytotoxic agents

A series of multisubstituted indole–acrylonitrile hybrids were designed, synthesized and evaluated for their potential cytotoxic activities. The bio-evaluation results indicated that some of the target compounds (such as 3a, 3f, 3k, 3n) exhibited good to moderate cytotoxic effect on HepG2, BCG-823, BEL-7402, and HL-7702 cell lines. Especially, the compounds 3a and 3k also exhibited high cytotoxic activities (3a, 19.38 ± 3.38 μM; 3k, 15.43 ± 3.54 μM) against the BEL-7402 cell line resistant to Taxol (>25 μM) and 5-FU (>500 μM), which might be developed as novel lead scaffold for potential anticancer agents.     

Synthesis and characterisation of celastrol derivatives as potential anticancer agents

In the present study, three series of novel celastrol derivatives were designed and synthesised by modifying the carboxylic acid at the 20th position with amino acid, amine, and triazole derivatives. All the synthesised compounds were screened for their anticancer activities using MTT assay against AGS, MGC-803, SGC-7901, HCT-116, A549, HeLa, BEL-7402, and HepG-2 cell lines. Most of the synthesised compounds exhibited potent antiproliferative effects. The most promising compound 3-Hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic amide, N-(R)-methyl-3-(1H-indol-2-yl)propanoate (11) showed considerable high anticancer activity against AGS cell lines, with an IC₅₀ value of 0.44?μM, and considerably higher activities against HCT-116, BEL-7402, and HepG-2 cell lines, with IC₅₀ values of 0.78, 0.63, and 0.76?μM, respectively. The results of apoptosis tests and molecular docking study of compound 11 binding to Caspase-3 revealed that its mechanism of action with antiproliferative was possibly involved in inducing apoptosis by inducing the activation of caspase-3.     

Cytotoxicity and modes of action of three naturally occurring xanthones (8-hydroxycudraxanthone G,morusignin I and cudraxanthone I) against sensitive and multidrug-resistant cancer cell lines

BackgroundResistance of cancer to chemotherapy remains a challenging issue for scientists as well as physicians. Naturally occurring xanthones possess a variety of biological activities such as anti-inflammatory, anti-bacterial, and anti-cancer effects. The present study was aimed at investigating the cytotoxicity and the modes of action of three naturally occurring xanthones namely, morusignin I (1), 8-hydroxycudraxanthone G (2) and cudraxanthone I (3) against a panel of nine cancer cell lines, including various sensitive and drug-resistant phenotypes.MethodsThe cytotoxicity of the compounds was determined using a resazurin reduction assay, whereas the caspase-Glo assay was used to detect the activation of caspases 3/7, caspase 8 and caspase 9 in cells treated with compounds 3. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells, analysis of mitochondrial membrane potential (MMP) as well as measurement of reactive oxygen species (ROS).ResultsCompounds 1 and 3 inhibited the proliferation of all tested cancer cell lines including sensitive and drug-resistant phenotypes. Compound 2 was active on 8/9 cell lines with the IC₅₀ values ranging from 16.65 μM (against leukemia CCRF-CEM cells) to 70.38 μM (against hepatocarcinoma HepG2 cells). The IC₅₀ value ranged from 7.15 μM (against CCRF-CEM cells) to 53.85 μM [against human glioblastoma U87MG.ΔEGFR cells] for compound 1, and from 2.78 μM (against breast cancer MDA-MB231 BCRP cells) to 22.49 μM (against U87MG cells) for compound 3. P-glycoprotein expressing CEM/ADR5000 cells were cross-resistant to compounds 1 and 2 (4.21- to 610-fold) while no cross-resistance or even collateral cross-sensitivity were observed in other drug-resistant cell lines to the three compounds. Normal AML12 liver cells were more resistant to the three compounds than HepG2 liver cancer cells. Compounds 3 arrested the cell cycle between G0/G1 and S phases, strongly induced apoptosis via caspases 3/7, caspase 8, caspase 9 activation and disrupted the MMP in CCRF-CEM cells.ConclusionsThe cytotoxicity of the studied xanthones and especially compound 3 deserve more detailed exploration in the future to develop novel anticancer drugs against sensitive and otherwise drug-resistant phenotypes.