A trans-platinum(II) complex induces apoptosis in cancer stem cells of breast cancer

Recent accumulating evidence has supported the notion that tumors have hierarchically organized heterogeneous cell populations and a small subpopulation of cells, termed cancer stem cells (CSCs), are responsible for tumor initiation, maintenance as well as drug resistance. Therefore, targeting the CSCs along with the other cancer cells has been the most important topic during the last decade. In the present study, we evaluated the cytotoxic activity of trans-[PtCl₂(2-hepy)₂] [2-hepy = 2-(2-hydroxyethyl) pyridine] complex and the mechanism of cell death in breast CSCs. Stemness markers, Oct-4 and Sox2, were determined in mammospheres by western blotting. Cytotoxicity was assessed using the ATP viability assay. Cell death was fluorescently visualized and further confirmed by flow cytometry as well as gene expression analysis. The Pt(II) complex significantly reduced the cell viability, prevented mammosphere formation and disrupted mammosphere structures in a dose-dependent manner (0–100 μM). The mode of cell death was apoptosis and it was shown by the presence of caspase 3/7 activity, Annexin V-FITC positivity, decreased mitochondrial membrane potential and increased expressions of pro-apoptotic genes (TNFRSF10A and HRK). Interestingly, necroptosis was also observed by the evidence of increased MLKL expression. In conclusion, the Pt(II) complex seems to be a highly promising anticancer compound due to its promising cytotoxic activity on CSCs. Therefore, it deserves in vivo further studies for the proof-of-concept.     

Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance

A major burden in the treatment of ovarian cancer is the high percentage of recurrence and chemoresistance. Cancer stem cells (CSCs) provide a reservoir of cells that can self-renew, can maintain the tumor by generating differentiated cells [non-stem cells (non-CSCs)] which make up the bulk of the tumor and may be the primary source of recurrence. We describe the characterization of human ovarian cancer stem cells (OCSCs). These cells have a distinctive genetic profile that confers them with the capacity to recapitulate the original tumor, proliferate with chemotherapy, and promote recurrence. CSC identified in EOC cells isolated form ascites and solid tumors are characterized by: CD44⁺, MyD88⁺, constitutive NFκB activity and cytokine and chemokine production, high capacity for repair, chemoresistance to conventional chemotherapies, resistance to TNFα-mediated apoptosis, capacity to form spheroids in suspension, and the ability to recapitulate in vivo the original tumor.

Chemotherapy eliminates the bulk of the tumor but it leaves a core of cancer cells with high capacity for repair and renewal. The molecular properties identified in these cells may explain some of the unique characteristics of CSCs that control self-renewal and drive metastasis. The identification and cloning of human OCSCs can aid in the development of better therapeutic approaches for ovarian cancer patients.     

Papyriferic acid derivatives as reversal agents of multidrug resistance in cancer cells

Forty-one derivatives of papyriferic acid were prepared based on our previous finding that methyl papyriferate (3) showed potent reversing effect on cytotoxicity of colchicine against multidrug resistance (MDR) human cancer cells (KB-C2), and evaluated for their cytotoxicity and effect on reversing P-gp-mediated MDR against KB-C2 cells. 3-O-(Morpholino-β-oxopropanoyl)-12β-acetoxy-3α,25-dihydroxy-(20S,24R)-epoxydammarane (37) significantly increased the sensitivity of colchicine against KB-C2 cells by 185-fold at 5 μg/mL (7.4 μM), and the cytotoxicity of colchicine was recovered to nearly that of sensitive (KB) cells. The other several new amide derivatives also exhibited potent reversal activity comparable to or more potent than methyl papyriferate and verapamil.     

CD166 promotes the cancer stem-like properties of primary epithelial ovarian cancer cells

Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In this study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166⁺ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers, including ALDH1a1, OCT4, and SOX2, and ABC transporters, which are implicated in the drug resistance of CSCs. The CD166⁺ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anti-cancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer.     

Design and synthesis of new triazoles linked to xanthotoxin for potent and highly selective anti-gastric cancer agents

Two series of xanthotoxin-triazole derivatives were designed, synthesized, and studied for their antiproliferative properties. The in vitro cytotoxicity of the compounds in the AGS cancer cell line and the L02 normal cell line was evaluated via MTT assay. Among the synthesized compounds, 9-((1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)-7H-furo[3,2-g]chromen-7-one (6p) was found to have the greatest antiproliferative activity against AGS cells (IC₅₀ = 7.5 μM) and showed better activity than the lead compound (xanthotoxin, IC₅₀ > 100 μM) and the reference drug (5-fluorouracil, IC₅₀ = 29.6 μM) did. The IC₅₀ value of 6p in L02 cells was 13.3 times higher than that in the AGS cells. Therefore, the compound exhibited better therapeutic activity and specificity compared with the positive control 5-fluorouracil. Cell cycle analysis revealed that compound 6p inhibited cell growth via the induction of S/G2 phase arrest in AGS cells. Compound 6p was identified as a promising lead compound for the further development and identification of 1,2,3-triazole-based anticancer agents.     

Cytotoxic pterosins from Pteris multifida roots against HCT116 human colon cancer cells

Two new pterosin glycosides, (2S,3S)-pterosin C 3-O-β-d-(4′-(E)-caffeoyl)-glucopyranoside (1) and (2S,3S)-pterosin C 3-O-β-d-(6′-(E)-p-coumaroyl)-glucopyranoside (2), were isolated from Pteris multifida (Pteridaceae) roots along with ten known pterosin compounds (3–12). The chemical structures of the isolated compounds were elucidated by extensive analysis of the 1D, 2D NMR, HRESIMS, and CD spectroscopic data. The cytotoxicities of 1–12 against HCT116 human colorectal cancer cell line were evaluated. Among the isolates, compound 1 showed moderate antiproliferative activity in HCT116 cells with an IC₅₀ value of 8.0 ± 1.7 μM. Additionally, 1 induced the upregulation of the caspase-9 and procaspase-9 levels in Western blots and increased the annexin V/propidium iodide (PI)-positive cell population in flow cytometry.     

Esculentin-2CHa: A host-defense peptide with differential cytotoxicity against bacteria,erythrocytes and tumor cells

The host-defense peptide, esculentin-2CHa (GFSSIFRGVA¹⁰KFASKGLGK D²⁰LAKLGVDLVA³⁰ CKISKQC) shows potent (MIC ≤ 6 μM) growth inhibitory activity against clinical isolates of multidrug-resistant strains of Staphylococcus aureus, Acinetobacter baumannii, and Stenotrophomonas maltophilia and differential cytotoxic activity against human erythrocytes (LC₅₀ = 150 μM) and human non-small cell lung adenocarcinoma A549 cells (LC₅₀ = 10 μM). Esculentin-2CHa significantly (P < 0.01) stimulates the release of the anti-inflammatory cytokine IL-10 by mouse lymphoid cells and elevates its production after stimulation with concanavalin A and significantly (P < 0.05) stimulates TNF-α production by peritoneal macrophages. Effects on IL-6 and IL-1β production were not significant. Removal of the hydrophobic N-terminal hexapeptide (GFSSIF) from esculentin-2CHa results in abolition of growth inhibitory activity against S. aureus and cytotoxic activity against erythrocytes and A549 cells as well as a marked (≥16-fold) reduction in potency against A. baumannii and S. maltophilia. The primary structure of esculentin-2 has been poorly conserved between frog species but evolutionary pressure has acted to maintain the hydrophobic character of this N-terminal hexapeptide sequence. Removal of the cyclic C-terminal domain (CKISKQC) and replacement of the Cys³¹ and Cys³⁷ residues by serine resulted in appreciable decreases in cytotoxicity against all microorganisms and against mammalian cells. The more cationic [D20K, D27K] analog showed a modest increase in potency against all microorganisms (up to 4-fold) but a marked increase in cytotoxicity against erythrocytes (LC₅₀ = 11 μM) and A549 cells (LC₅₀ = 3 μM).     

Anti-inflammatory norditerpenoids from the soft coral Sinularia maxima

Chemical investigation of the soft coral Sinularia maxima resulted in the isolation of seven norditerpenoids, including two new compounds, 12-hydroxy-scabrolide A (2) and 13-epi-scabrolide C (6). The structures of the isolated compounds were elucidated based on extensive spectroscopic evidence including Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and both one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR, respectively), in comparison with reported data. Compound 6 potently inhibited IL-12 and IL-6 production in LPS-stimulated bone marrow derived dendritic (BMDCs) with IC₅₀ values of 5.30 ± 0.21 and 13.12 ± 0.64 μM, respectively. Compound 1 exhibited moderate inhibitory activity against IL-12 and IL-6 production with IC₅₀ values of 23.52 ± 1.37 and 69.85 ± 4.11 μM, respectively.     

Novel dammarane saponins from Gynostemma pentaphyllum and their cytotoxic activities against HepG2 cells

Two new dammarane saponins, 2α,3β,12β-trihydroxydammar-20(22),24-diene-3-O-[β-d-glucopyranoxyl(1→2)-β-d-6″-O-acetylglucopyranoside (1, namely damulin C) and 2α,3β,12β-trihydroxydammar-20(21),24-diene-3-O-[β-d-glucopyranoxyl(1→2)-β-d-6″-O-acetylglucopyranoside (2, namely damulin D), were isolated from the ethanol extract of Gynostemma pentaphyllum, which had been heat processed by steaming at 125 °C. The NMR spectroscopic data of the novel saponins were completely assigned by using a combination of 2D NMR experiments including ¹H–¹H COSY, HSQC, and HMBC. Their cytotoxic activities of human liver adenocarcinoma HepG2 cells were evaluated in vitro. They showed cytotoxicities against HepG2 cell line with IC₅₀ of 40 ± 0.7 and 38 ± 0.5 μg/ml, respectively.     

Synthesis and antiproliferative evaluation of certain indolo[3,2-c]quinoline derivatives

The present report describes the synthesis and antiproliferative evaluation of certain indolo[3,2-c]quinoline derivatives. For the C₆ anilino-substituted derivatives, (11H-indolo[3,2-c]quinolin-6-yl)phenylamine (6a) was inactive. Structural optimization of 6a by the introduction of a hydroxyl group at the anilino-moiety resulted in the enhancement of antiproliferative activity in which the activity decreased in an order of para-OH, 7a > meta-OH, 8a > ortho-OH, 9a. For the C₆ alkylamino-substituted derivatives, 11a, 12a, 13a, 14a, and 15a exhibited comparable antiproliferative activities against all cancer cells tested and the skin Detroit 551 normal fibroblast cells. Three cancer cells, HeLa, A549, and SKHep, are very susceptible with IC₅₀ of less than 2.17 μM while PC-3 is relatively resistant to this group of indolo[3,2-c]quinolines. For the 2-phenylethylamino derivatives, compound 20a is active against the growth of HeLa with an IC₅₀ of 0.52 μM, but is less effective against the growth of Detroit 551 with an IC₅₀ of 19.32 μM. For the bis-indolo[3,2-c]quinolines, N,N-bis-[3-(11H-indolo[3,2-c]quinolin-6-yl)aminopropyl]amine hydrochloride (25) is more active than its N-methyl derivative 26 and the positive Doxorubicin. Mechanism studies indicated 25 can induce caspase-3 activation, γ-H2AX phosphorylation, cleavage of poly(ADP-ribose)polymerase and DNA fragmentation. These results provide evidence that DNA, topo I, and topo II are the primary targets of indolo[3,2-c]quinoline derivatives and that consequently inhibits proliferation and causes apoptosis in cancer cells.     

Salinomycin Promotes Anoikis and Decreases the CD44+/CD24- Stem-Like Population via Inhibition of STAT3 Activation in MDA-MB-231 Cells

Triple-negative breast cancer (TNBC) is an aggressive tumor subtype with an enriched CD44⁺/CD24^- stem-like population. Salinomycin is an antibiotic that has been shown to target cancer stem cells (CSC); however, the mechanisms of action involved have not been well characterized. The objective of the present study was to investigate the effect of salinomycin on cell death, migration, and invasion, as well as CSC-like properties in MDA-MB-231 breast cancer cells. Salinomycin significantly induced anoikis-sensitivity, accompanied by caspase-3 and caspase-8 activation and PARP cleavage, during anchorage-independent growth. Salinomycin treatment also caused a marked suppression of cell migration and invasion with concomitant downregulation of MMP-9 and MMP-2 mRNA levels. Notably, salinomycin inhibited the formation of mammospheres and effectively reduced the CD44⁺/CD24^- stem-like population during anchorage-independent growth. These observations were associated with the inhibition of STAT3 phosphorylation (Tyr705). Furthermore, interleukin-6 (IL-6)-induced STAT3 activation was strongly suppressed by salinomycin challenge. These findings support the notion that salinomycin may be potentially efficacious for targeting breast cancer stem-like cells through the inhibition of STAT3 activation.     

Anti-inflammatory activity of flavonoids from Chrozophora tinctoria

Chemical investigation of Chrozophora tinctoria (L.) A. Juss. growing in Saudi Arabia revealed the isolation of two new acylated flavonoids identified as acacetin-7-O-β-d-[α-l-rhamnosyl(1 → 6)]3″-E-p-coumaroyl glucopyranoside (4) and apigenin-7-O-(6″-Z-p-coumaroyl)-β-d-glucopyranoside (5), in addition to amentoflavone (1), apigenin-7-O-β-d-glucopyranoside (2), apigenin-7-O-6″-E-p-coumaroyl-β-d-glucopyranoside (3) and rutin (6). The structures of isolated compounds were established by 1D, 2D NMR and HRESIMS spectral data, in addition to comparison with literature data. The anti-inflammatory activities of isolated compounds were assessed by measuring the levels of IL-1β, IL-6, TNF-α and PGE₂ in the supernatant media of human peripheral blood mononuclear cells (PBMCs) stimulated by phytohaemagglutinin (PHA). At a concentration of 100 μM, compounds 1, 2, 4 and 6 significantly decreased Il-1β, Il-6 and PGE₂ to nearly normal values. All tested compounds caused a dose-dependent decrease in TNF-α level but failed to reach that of the control values.     

Activity of three cytotoxic isoflavonoids from Erythrina excelsa and Erythrina senegalensis (neobavaisoflavone,sigmoidin H and isoneorautenol) toward multi-factorial drug resistant cancer cells

IntroductionResistance of cancer cells to chemotherapy has become a worldwide concern. Naturally occuring isoflavonoids possess a variety of biological activities including anti-cancer effects. The present study was aimed at investigating the cytotoxicity and the modes of action of three naturally occuring isoflavonoids, neobavaisoflavone (1), sigmoidin H (2) and a pterocarpan that is a special type of isoflavonoid, isoneorautenol (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 3 showed significant cytotoxicity toward sensitive and drug-resistant cancer cell lines. Compounds 1 and 2 were selectively active, and IC50 values below 115 μM were obtained on 6/9 and 4/9 cell lines respectively with values ranging from 42.93 μM (toward CCRF-CEM cells) to 114.64 μM [against HCT116 (p53^+/+) cells] for 1 and 25.59 μM (toward U87MG) to 110.51 μM [against HCT116 (p53^+/+) cells] for 2. IC50 values ranging from 2.67 μM (against MDA-MB 237BCRP cells) to 21.84 (toward U87MG) were measured for compound 3 and between 0.20 μM (toward CCRF-CEM cells) and 195.12 μM (toward CEM/ADR5000 cells) for doxorubicin as control drug. BCRP-transfected MDA-MB-231 cells, HCT116 (p53^+/+) and U87MG.ΔEGFR cells were hypersensitive (collateral sensitive) to compound 3 as compared to their counterpart cell lines. Compound 3 induced apoptosis in CCRF-CEM cells via activation of caspases 3/7, 8 and 9 as well as the loss of MMP and increased ROS production.ConclusionsThe cytotoxicity of the studied isoflavonoids and especially the pterocarpan 3 deserve more detailed exploration in the future to develop novel anticancer drugs against sensitive and otherwise drug-resistant phenotypes.     

Membrane androgen receptor sensitive Na+/H+ exchanger activity in prostate cancer cells

Membrane androgen receptors (mAR) are expressed in several tumors. mAR activation by testosterone albumin conjugates (TAC) suppresses tumor growth and migration. mAR signaling involves phosphoinositide-3-kinase (PI3K) and Rho-associated protein kinase (ROCK). PI3K stimulates serum- and glucocorticoid-inducible kinase SGK1, which in turn activates Na⁺/H⁺-exchangers (NHE). In prostate cancer cells cytosolic pH (pH_i) was determined utilizing 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein-fluorescence and NHE-activity utilizing Na⁺-dependent cytosolic realkalinization following an ammonium pulse. TAC (100 nM) significantly increased pH_i and NHE-activity, effects abrogated by NHE1-inhibitor cariporide (10 μM), SGK1-inhibitors EMD638683 (50 μM) and GSK650349 (10 μM) and ROCK-inhibitors Y-27632 (10 μM) and fasudil (100 μM). TAC treatment rapidly and significantly increased cell volume and actin polymerization, effects abolished in the presence of cariporide. Thus, mAR-activation activates cariporide-sensitive Na⁺/H⁺-exchangers, an effect requiring SGK1 and ROCK activity.     

A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer

BackgroundNatural killer (NK) cells derived from patients with cancer exhibit diminished cytotoxicity compared with NK cells from healthy individuals. We evaluated the tumor response and in vivo expansion of allogeneic NK cells in recurrent ovarian and breast cancerMethodsPatients underwent a lymphodepleting preparative regimen: fludarabine 25 mg/m² × 5 doses, cyclophosphamide 60 mg/kg × 2 doses, and, in seven patients, 200 cGy total body irradiation (TBI) to increase host immune suppression. An NK cell product, from a haplo-identical related donor, was incubated overnight in 1000 U/mL interleukin (IL)-2 prior to infusion. Subcutaneous IL-2 (10 MU) was given three times/week × 6 doses after NK cell infusion to promote expansion, defined as detection of ≥100 donor-derived NK cells/μL blood 14 days after infusion, based on molecular chimerism and flow cytometryResultsTwenty (14 ovarian, 6 breast) patients were enrolled. The median age was 52 (range 30–65) years. Mean NK cell dose was 2.16 × 10⁷cells/kg. Donor DNA was detected 7 days after NK cell infusion in 9/13 (69%) patients without TBI and 6/7 (85%) with TBI. T-regulatory cells (Treg) were elevated at day +14 compared with pre-chemotherapy (P = 0.03). Serum IL-15 levels increased after the preparative regimen (P = < 0.001). Patients receiving TBI had delayed hematologic recovery (P = 0.014). One patient who was not evaluable had successful in vivo NK cell expansionConclusionsAdoptive transfer of haplo-identical NK cells after lymphodepleting chemotherapy is associated with transient donor chimerism and may be limited by reconstituting recipient Treg cells. Strategies to augment in vivo NK cell persistence and expansion are needed.     

Scaffold-switching: An exploration of 5,6-fused bicyclic heteroaromatics systems to afford antituberculosis activity akin to the imidazo[1,2-a]pyridine-3-carboxylates

A set of 5,6-fused bicyclic heteroaromatic scaffolds were investigated for their in vitro anti-tubercular activity versus replicating and non-replicating strains of Mycobacterium tuberculosis (Mtb) in an attempt to find an alternative scaffold to the imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidines that were previously shown to have potent activity against replicating and drug resistant Mtb. The five new bicyclic heteroaromatic scaffolds explored in this study include a 2,6-dimethylimidazo[1,2-b]pyridazine-3-carboxamide (7), a 2,6-dimethyl-1H-indole-3-carboxamide (8), a 6-methyl-1H-indazole-3-carboxamide (9), a 7-methyl-[1,2,4]triazolo[4,3-a]pyridine-3-carboxamide (10), and a 5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide (11). Additionally, imidazo[1,2-a]pyridines isomers (2 and 12) and a homologous imidazo[1,2-a]pyrimidine isomer (6) were prepared and compared. Compounds 2 and 6 were found to be the most potent against H₃₇Rv Mtb (MIC’s of 0.1 μM and 1.3 μM) and were inactive (MIC >128 μM) against Staphylococcus aureus, Escherichia coli and Candida albicans. Against other non-tubercular mycobacteria strains, compounds 2 and 6 had activity against Mycobacterium avium (16 and 122 μM, respectively), Mycobacterium kansasii (4 and 19 μM, respectively), Mycobacterium bovis BCG (1 and 8 μM, respectively) while all the other scaffolds were inactive (>128 μM).     

Isolation,structural characterization and neuraminidase inhibitory activities of polyphenolic constituents from Flos caryophylli

Neuraminidase (NA) is one of the key surface proteins of the influenza virus, which is an important target for anti-influenza therapy. In the present study, bioassay-guided fractionation led to isolation of two new compounds, rhamnetin-3-O-β-d-glucuronide-6″-methyl ester (1) and rhamnazin-3-O-β-d-glucuronide-6″-methyl ester (2), along with seventeen known compounds (3-19), from the MeOH extract of Flos Caryophylli using in vitro NA inhibition assay. These isolated compounds exhibited significantly inhibitory effects on the NA with IC₅₀ values ranging from 8.4 to 94.1 μM and were found to protect MDCK cells from A (H1N1) influenza infections (EC₅₀ = 1.5–84.7 μM) with very low cytotoxicity to the host cells (CC₅₀ = 374.3–1266.9 μM)), with selective index (SI) ranging from 7 to 297. The primary structure-relationships of these isolates were also discussed.     

Design,synthesis and biological evaluation of indeno[1,2-d]thiazole derivatives as potent histone deacetylase inhibitors

Novel indeno[1,2-d]thiazole hydroxamic acids were designed, synthesized, and evaluated for histone deacetylases (HDACs) inhibition and antiproliferative activities on tumor cell lines. Most of the tested compounds exhibited HDAC inhibition and antiproliferative activity against both MCF7 and HCT116 cells with GI₅₀ values in the sub-micromolar range. Among them, compound 6o showed good inhibitory activity against pan-HDAC with IC₅₀ value of 0.14 μM and significant growth inhibition on MCF7 and HCT116 cells with GI₅₀ values of 0.869 and 0.535 μM, respectively.     

In vitro cytotoxic activity of isolated acridones alkaloids from Zanthoxylum leprieurii Guill. et Perr

Chemical investigation of the roots and fruits of Zanthoxylum leprieurii Guill. et Perr. led to the isolation of three new alkaloids including two acridone derivatives, 3-hydroxy-1,4-dimethoxy-10-methyl-9-acridone (2) and 3-hydroxy-1,2-dimethoxy-10-methyl-9-acridone (3) named helebelicine A and B, respectively, and one secobenzo[c]phenantridine, 10-O-demethyl-12-O-methylarnottianamide (10), together with thirteen other compounds. The structures of compounds 2, 3 and 10 as well as those of the known compounds were elucidated by using spectroscopic methods and by comparison with reported data. The brine-shrimp (artemia salina) lethality bioassay of the chloroform extract of the fruits showed modest cytotoxicity with LD₅₀ at 13.1 μg/mL. Isolated compounds 1, 4–6 were found to be moderately active against lung carcinoma cells (A549), colorectal adenocarcinoma cells (DLD-1) and normal cells (WS1) with IC₅₀ values ranging from 27 to 77 μM. In contrast to the positive control etoposide used, the cytotoxicity of the most active compound 4 was found to be selective against cancer cells in comparison to normal cells WS1 with IC₅₀ of 51 ± 8 μM and 4.3 ± 0.4 μM, respectively.