Cancer Cell Line HCT116 Research Articles

Antiproliferative Activities of Acetone Extract From Canarium Odontophyllum (Dabai) Stem Bark Against Human Colorectal Cancer Cells.

Colorectal cancer is the most common malignant cancer in developing countries. Canarium odontophyllum, also known as "Dabai" or "Borneo Olive" is among the natural plants that can potentially be used as an anticancer agent. This study aims to determine the antiproliferative activities and cytotoxicity effects of acetone extract from C. odontophyllum stem bark against human colorectal cancer cell lines HCT 116 and HT 29. Acetone extract of C. odontophyllum stem bark exerted a significant cytotoxic effect on HCT 116 and HT 29 cells determined by MTT assay at the concentration of 12.5μg/mL to 200μg/mL for 24, 48, and 72hours treatment. It was found that acetone extract of C. odontophyllum stem bark inhibited proliferation of HCT 116 with an IC50 value of 184.93 ± .0μg/mL, 61.24 ± .1μg/mL, 79.98 ± .029 for 24, 48 and 72hours respectively. The findings also showed that acetone extract of C. odontophyllum stem bark revealed a lower inhibitory effect against HT-29 with an IC50 value of more than 200μg/mL for 24, 48 and 72hours. However, acetone extract of C. odontophyllum stem bark at similar concentrations and time points did not show any cytotoxic effect to normal colorectal fibroblast cell CCD18-Co. In conclusion, the acetone extract of C. odontophyllum stem bark exhibited more sensitivity against HCT 116 than HT 29. Its antiproliferative ability towards HCT 116 and HT 29 cells provides insight that this extract may serve as an anticancer agent against colorectal cancer.

Design, synthesis, molecular docking studies and biological evaluation of thiazole carboxamide derivatives as COX inhibitors

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) have been the most commonly used class of medications worldwide for the last three decades.ObjectivesThis study aimed to design and synthesize a novel series of methoxyphenyl thiazole carboxamide derivatives and evaluate their cyclooxygenase (COX) suppressant and cytotoxic properties.MethodsThe synthesized compounds were characterized using 1H, 13C-NMR, IR, and HRMS spectrum analysis and were evaluated for their selectivity towards COX-1 and COX-2 using an in vitro COX inhibition assay kit. Besides, their cytotoxicity was evaluated using the Sulforhodamine B (SRB) assay. Moreover, molecular docking studies were conducted to identify the possible binding patterns of these compounds within both COX-1 and COX-2 isozymes, utilizing human X-ray crystal structures. The density functional theory (DFT) analysis was used to evaluate compound chemical reactivity, which was determined by calculating the frontier orbital energy of both HOMO and LUMO orbitals, as well as the HOMO–LUMO energy gap. Finally, the QiKProp module was used for ADME-T analysis.ResultsThe results revealed that all synthesized molecules have potent inhibitory activities against COX enzymes. The percentage of inhibitory activities at 5 µM concentration against the COX2 enzyme was in the range of 53.9–81.5%, while the percentage against the COX-1 enzyme was 14.7–74.8%. That means almost all of our compounds have selective inhibition activities against the COX-2 enzyme, and the most selective compound was 2f, with selectivity ratio (SR) value of 3.67 at 5 µM concentration, which has a bulky group of trimethoxy on the phenyl ring that could not bind well with the COX-1 enzyme. Compound 2h was the most potent, with an inhibitory activity percentage at 5 µM concentration of 81.5 and 58.2% against COX-2 and COX-1, respectively. The cytotoxicity of these compounds was evaluated against three cancer cell lines: Huh7, MCF-7, and HCT116, and negligible or very weak activities were observed for all of these compounds except compound 2f, which showed moderate activities with IC50 values of 17.47 and 14.57 µM against Huh7 and HCT116 cancer cell lines, respectively. Analysis of the molecular docking suggests 2d, 2e, 2f, and 2i molecules were bound to COX-2 isozyme favorably over COX-1 enzyme, and their interaction behaviors within COX-1 and COX-2 isozymes were comparable to celecoxib, as an ideal selective COX-2 drug, which explained their high potency and COX-2 selectivity. The molecular docking scores and expected affinity using the MM-GBSA approach were consistent with the recorded biological activity. The calculated global reactivity descriptors, such as HOMO and LUMO energies and the HOMO–LUMO gaps, confirmed the key structural features required to achieve favorable binding interactions and thus improve affinity. The in silico ADME-T studies asserted the druggability of molecules and have the potential to become lead molecules in the drug discovery process.ConclusionIn general, the series of the synthesized compounds had a strong effect on both enzymes (COX-1 and COX-2) and the trimethoxy compound 2f was more selective than the other compounds.

Hypericum foliosum Quality Botanical and Chemical Markers and In Vitro Antioxidant and Anticancer Activities.

Hypericum foliosum Aiton is an endemic Azorean Hypericum species. Even though the aerial parts of Hypericum foliosum are not described in any official pharmacopoeia, they are utilized in local traditional medicine due to their diuretic, hepatoprotective, and antihypertensive properties. This plant has previously been the subject of phytochemical characterization and has been studied for its antidepressant activity, showing significant results in animal models. The lack of a description of the main characteristics of the aerial parts, which would be necessary to properly identify this medicinal plant species, contributes to the possibility of misidentification events. We performed macroscopic and microscopic analyses that identified specific differential characteristics, such as the absence of dark glands, the dimensions of the secretory pockets in the leaf, and the presence of translucent glands in the powder. To continue our previous work on the biological activity of Hypericum foliosum, ethanol, dichloromethane/ethanol, and water extracts were prepared and studied for their antioxidant and cytotoxic activity. Extracts showed in vitro selective cytotoxic activity in human lung cancer cell line A549, colon cancer cell line HCT 8, and breast cancer cell line MDA-MB-231, with dichloromethane/ethanol showing higher activity against all cell lines (IC50 values of 71.49, 27.31, and 9.51 µg/mL, respectively). All extracts also showed significant antioxidant activity.

Aculeaxanthones A-E, new xanthones from the marine-derived fungus Aspergillus aculeatinus WHUF0198.

Dimeric natural products are widespread in plants and microorganisms, which usually have complex structures and exhibit greater bioactivities than their corresponding monomers. In this study, we report five new dimeric tetrahydroxanthones, aculeaxanthones A-E (4-8), along with the homodimeric tetrahydroxanthone secalonic acid D (1), chrysoxanthones B and C (2 and 3), and 4-4'-secalonic acid D (9), from different fermentation batches of the title fungus. A part of the culture was added to a total of 60 flasks containing 300 ml each of number II fungus liquid medium and culture 4 weeks in a static state at 28˚C. The liquid phase (18 L) and mycelia was separated from the fungal culture by filtering. A crude extract was obtained from the mycelia by ultrasound using acetone. To obtain a dry extract (18 g), the liquid phase combined with the crude extract were further extracted by EtOAc and concentrated in vacuo. The MIC of anaerobic bacteria was examined by a broth microdilution assay. To obtain MICs for aerobic bacteria, the agar dilution streak method recommended in Clinical and Laboratory Standards Institute document (CLSI) M07-A10 was used. Compounds 1-9 was tested against the Bel-7402, A-549 and HCT-116 cell lines according to MTT assay. The structures of these compounds were elucidated on the base of 1D and 2D NMR and HR-ESIMS data, and the absolute configurations of the new xanthones 4-8 were determined by conformational analysis and time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. Compounds 1-9 were tested for cytotoxicity against the Bel-7402, A549, and HCT-116 cancer cell lines. Of the dimeric tetrahydroxanthone derivatives, only compound 6 provided cytotoxicity effect against Bel-7402 cell line (IC50, 1.96 µM). Additionally, antimicrobial activity was evaluated for all dimeric tetrahydroxanthones, including four Gram-positive bacteria including Enterococcus faecium ATCC 19434, Bacillus subtilis 168, Staphylococcus aureus ATCC 25923 and MRSA USA300; four Gram-negative bacteria, including Helicobacter pylori 129, G27, as well as 26,695, and multi drug-resistant strain H. pylori 159, and one Mycobacterium M. smegmatis ATCC 607. However, only compound 1 performed activities against H. pylori G27, H. pylori 26695, H. pylori 129, H. pylori 159, S. aureus USA300, and B. subtilis 168 with MIC values of 4.0, 4.0, 2.0, 2.0, 2.0 and 1.0 μg/mL, respectively.

Low-dimensional compounds containing bioactive ligands. Part XXI: Crystal structures, cytotoxic, antimicrobial activities and BSA binding of zinc complexes with 5-chloro-7-nitro-8-hydroxyquinoline

Four new zinc(II) complexes containing molecules of 5-chloro-7-nitro-8-hydroxyquinoline (HClNQ), NH2(CH3)2[Zn(ClNQ)3]·DMF (1), K[Zn(ClNQ)3]·2DMF (2), {Na[Zn(ClNQ)(SO4)(H2O)]}n (3) and [Zn(ClNQ)2(H2O)2] (4), were prepared and characterized by IR and NMR spectroscopy, elemental analysis and single crystal X-ray analysis. Ionic complexes 1 and 2 have similar structures, in which Zn(II) atoms are coordinated by three chelate molecules of ClNQ via oxygen and nitrogen donor atoms forming rare fac isomers. The negative charge of the complex anions is balanced by uncoordinated NH2(CH3)2+ (1) and K+ cations (2). Complex 3 has a polymeric structure in which Zn(II) atom is penta-coordinated by one chelate molecule of ClNQ, one molecule of water and a pair of crystallographically equivalent sulfato ligands, which interconnect adjacent zinc atoms to form a zig-zag chain. The negative charge of the chain is balanced by sodium cations. In a molecular complex 4, equatorial plane is occupied by two chelate ClNQ molecules with nitrogen and oxygen atoms of the two ligands in an infrequent cis-arrangement and axial positions of a distorted octahedron occupy two aqua ligands. HClNQ and complexes 1, 3 and 4 were tested for their antiproliferative activity against HeLa, A549, MCF-7, MDA-MB-231, HCT-116 and Caco-2 cancer cell lines and their selectivity was verified using Cos-7 non-cancerous cell line. The results showed that the complexes exhibited poor nonselective antiproliferative activity. Antibacterial activity of HClNQ and complexes 1, 3 and 4 were tested, too. RIZD (relative inhibition zone diameter) and MIC (minimal inhibitory concentration) showed that complexes 1, 4 and HClNQ inhibited gram-positive bacteria S. aureus. Against gram-negative bacteria E. coli, only HClNQ and 1 were effective in tested concentration. Finally, BSA binding activity of complexes 1 – 4 was investigated by fluorescence quenching measurements.

Synthesis and characterization of cellulose functionalized zeolitic diatomite as an enhanced carrier of oxaliplatin drug; loading, release, and cytotoxicity

Natural diatomite frustules (D) were incorporated in zeolitization and cellulose functionalization processes to obtain zeolitized diatomite (ZD) and cellulose fibrous/zeolitized diatomite composite (CF/ZD). The modified products were assessed as potential carriers of oxaliplatin drug (OXPL) with enhanced properties. The prepared ZD (112.5 mg/g) and CF/ZD (268.3 mg/g) structures exhibit significantly enhanced encapsulation capacities as compared to raw diatomite (65.9 mg/g). The occurred encapsulation reactions follow the classic Pseudo-first order kinetic (R2 > 0.93) and traditional Langmuir isotherm (R2 = 0.99). The estimated effective encapsulation site density of CF/ZD is 104.8 mg/g which is a notably higher value than ZD (44.6 mg/g) and D (28.4 mg/g). Moreover, each effective site can be occupied with up to 3 molecules of OXPL molecules in vertical forms involving multi-molecular mechanisms. The encapsulation energy (<40 KJ/mol) suggested the predominant effects of the physical mechanisms during the encapsulation reactions. The release profiles of ZD as well as CF/ZD exhibit slow and controlled properties for about 100 h either at pH 5.5 or at pH 7.4. The release kinetic studies involving the obtained diffusion exponent values (>0.45) suggested non-Fickian transport and complex erosion/diffusion release mechanism. These structures exhibit enhanced cytotoxic effects on the HCT-116 cancer cell lines (D (18.78 % cell viability), ZD (9.76 % cell viability), and CF/ZD (3.16 % cell viability).

Cytotoxic Evaluation of Doxorubicin Combination with Baicalein and Resveratrol Against Hct116 and Hepg2 Cancer Cell Lines (Conference Paper) #

Combination of natural poly-phenolic compounds with chemotherapeutic agents is recently being a novel strategy in cancer therapy researches owing to their potential antioxidant and anti-inflammatory properties that modulate several intracellular signaling pathways.&#x0D; Resveratrol and Baicalein are well known poly-phenolic compounds that belong to stilbene and flavone subclasses, respectively.&#x0D; This study aims to investigate the possible enhancement effect of resveratrol and Baicalein when combined with doxorubicin using a different combination ratio and applied on two cancer cell lines: HCT116 (colorectal cancer cells) and HepG2 (hepatocellular cancer cells). It also investigates the possibility of such natural compounds to provide a protection effect on cardiocytes (H9C2) when resveratrol and Baicalein treatment followed by doxorubicin is used. &#x0D; The two cancer cell lines were treated with different combination groups, including the combination between doxorubicin and Baicalein or resveratrol and the combination between the three compounds using a different combination ratio for both treatment groups (i.e., two drugs or three drugs combination). Treatment applied on cells, using cell density of 7000 cells /well and incubation time was 48 hrs. MTT test was performed to assay the cell viability.&#x0D; The results obtained showed that the cytotoxicity of doxorubicin in the two cancer cell lines has increased when combined with Baicalein and resveratrol. Doxorubicin IC50 decreased from 4.99 µg/ml to 0.3657 µg/ml and from 7.3 µg/ml to 0.676 µg/ml on HCT116 and HepG2 cells, respectively, using constant combination ratio (1:1:1).&#x0D; The combination of doxorubicin, Baicalein, and resveratrol has resulted in a less cardiotoxic effect compared to treatment with doxorubicin alone. This decrease was obviously seen when the three compounds were combined using a low concentration range and with a constant combination ratio.&#x0D; Conclusion: combinations of Baicalein and resveratrol with doxorubicin chemotherapeutic drug In Vitro had enhanced the cytotoxic activity of such a chemotherapeutic drug, while simultaneously eliminating its cardio-toxicity side effect.&#x0D;

Design, Synthesis, Molecular docking, and biological evaluation of novel 2,3-diaryl-1,3-thiazolidine-4-one derivatives as potential anti-inflammatory and cytotoxic agents

A new series of 2,3-diaryl-1,3thiazolidin-4-one derivatives was designed, synthesized, and evaluated for their cytotoxicity and COXs inhibitory activities. Among these derivatives, compounds 4 k and 4j exhibited the highest inhibitory activities against COX-2 at IC50 values of 0.05 and 0.06 μM, respectively. Compounds 4a, 4b, 4e, 4 g, 4j, 4 k, 5b, and 6b, which exhibited the highest inhibition% against COX-2, were evaluated for their anti-inflammatory activity in rats. Results showed 41.08–82.00 % inhibition of paw edema thickness by the test compounds compared to celecoxib (inhibition% = 89.51 %). In addition, compounds 4b, 4j, 4 k, and 6b exhibited better GIT safety profiles compared to celecoxib and indomethacin. The four compounds were also evaluated for their antioxidant activity. The results revealed the highest antioxidant activity for 4j (IC50 = 45.27 μM) comparable to torolox (IC50 = 62.03 μM). The antiproliferative activity of the new compounds was evaluated against HePG-2, HCT-116, MCF-7, and PC-3 cancer cell lines. The results showed the highest cytotoxicity for compounds 4b, 4j, 4 k, and 6b (IC50 = 2.31–27.19 μM), with 4j being the most potent. Mechanistic studies revealed the ability of 4j and 4 k by inducing marked apoptosis and cell cycle arrest at the G1 phase in HePG-2 cancer cells. These biological results may also suggest a role for COX-2 inhibition in the antiproliferative activity of these compounds. The results of the molecular docking study for 4 k and 4j into the active site of COX-2 revealed good fitting and correlation with the results of the in vitro COX‑2 inhibition assay.

In Vitro Anticancer Activity of Hexane and Ethyl acetate Extracts of Leaf, Petiole and Rhizome of Petasites japonicus

The aim of this study was to ascertain the effect of different solvents on extraction yield,&nbsp;antioxidant activity and cytotoxicity of extracts from Petasites japonicus (Siebold &amp; Zucc.) Maxim. P. japonicus, widely distributed in Korea, Japan and China, is used as a culinary vegetable and a traditional medicine for asthma, migraines and tension headaches, and allergic rhinitis. In this study, twelve extracts from leaves, petioles and rhizomes of P. japonicus were evaluated for their antiproliferative activity against AGS, HepG2, HCT-116, and MCF-7 cancer cell lines. Plant extracts were fractionated using hexane, EtOAc, BuOH and distilled water, after which the antiproliferative activity was measured by MTT assay. Cell viability decreased in a dose dependent manner in response to the hexane and ethyl acetate extracts for all cell lines, with a significant decrease in cell viability being observed for 100 μg/ml and 75 μg/ml in the AGS and HepG2 cancer cell lines (p &lt; 0.05). The leaf extract appeared to be more potent against HepG2, as indicated by IC50 values of 4.31 μg/ml for approximately 2.5- and 6.3-fold compared with rhizome and petiole extracts, respectively. The IC50 values of hexane extracts from leaves and&nbsp;rhizomes against AGS, HepG2, and MCF-7 human cell lines were greater than those of other extracts, while ethyl acetate extracts from petioles showed higher significant effect for all cell lines. Hexane and EtOAc extracts exerted their antiproliferative activity in four cancer cell lines. Overall, the results indicate that P. japonicus has the potential to be developed into selective anticancer nutraceutical and/or pharmaceutical treatments with low cost.

Synthesis, molecular docking study and anticancer activity of novel 1,3,4-oxadiazole derivatives as potential tubulin inhibitors

The current study reports on the synthesis and anticancer efficacy of novel oxadiazole derivatives (8a-f) as tubulin polymerization inhibitors. NMR, mass, and elemental studies were used to confirm the newly produced compounds. In contrast to the conventional medicine colchicine, compounds 8e and 8f demonstrated stronger sensitivity and improved IC50 values in the range of 3.19–8.21 μM against breast MCF-7, colorectal HCT116, and liver HepG2 cancer cell lines. The target compounds were tested for enzymatic activity against the tubulin enzyme. Compounds 8e and 8f were shown to have the most effective inhibitory action among the new compounds, with IC50 values of 7.95 and 9.81 nM, respectively. As compared to the reference drug, molecular docking investigations of the developed compounds revealed the crucial hydrogen bonding in addition to the hydrophobic interaction at the binding site, assisting in the prediction of the structural requirements for the found anticancer activity. These findings indicate that the 1,3,4-oxadizole scaffold has the potential for future research into new anticancer medicines.

New [1,2,4]triazolo[4,3-c]quinazolines as intercalative Topo II inhibitors: Design, synthesis, biological evaluation, and in silico studies.

Fifteen quinazoline derivatives were designed and synthesized as DNA intercalators. The cytotoxicity of the designed members was assessed against HCT-116 and HepG2 cancer cell lines. In addition, the topoisomerase II (Topo II) inhibitory effect was assessed. Compound 16 was the most cytotoxic and Topo II inhibitor with low cytotoxicity against Vero cells. Compounds 16, 17, and 18 showed significant DNA binding affinities. Compound 16 showed Topo II catalytic inhibitory effect at a concentration of 10 μM. Further mechanistic investigations revealed the capability of compound 16 to induce apoptosis in HCT-116 cells and arrest the growth at the S and G2/M phases. Also, compound 16 showed a significant increase in the level of BAX (2.18-fold) and a marked decrease in the level of Bcl-2 (1.9-fold) compared to the control cells. In silico studies revealed the ability of the synthesized members to bind to the DNA-Topo II complex.

Two new sarasinosides from marine sponge Petrosia nigricans

Two new sarasinosides designated as 5,8-epoxysarasinoside (1) and 8,9-epoxysarasinoside (2) and four known sarasinosides were isolated from marine sponge Petrosia nigricans, collected off the coast of Lipata, Surigao City, Philippines (9°49' North, 125°27' East). The structures were determined through extensive 2D NMR spectroscopy and HRMS. Both compounds exhibited low cytotoxicity against the HCT116 (colon) and A549 (lung) cancer cell lines.

Synthesis and Biological Evaluation of Novel Dispiro-Indolinones with Anticancer Activity.

Novel variously substituted thiohydantoin-based dispiro-indolinones were prepared using a regio- and diastereoselective synthetic route from 5-arylidene-2-thiohydantoins, isatines, and sarcosine. The obtained molecules were subsequently evaluated in vitro against the cancer cell lines LNCaP, PC3, HCTwt, and HCT(-/-). Several compounds demonstrated a relatively high cytotoxic activity vs. LNCaP cells (IC50 = 1.2-3.5 µM) and a reasonable selectivity index (SI = 3-10). Confocal microscopy revealed that the conjugate of propargyl-substituted dispiro-indolinone with the fluorescent dye Sulfo-Cy5-azide was mainly localized in the cytoplasm of HEK293 cells. P388-inoculated mice and HCT116-xenograft BALB/c nude mice were used to evaluate the anticancer activity of compound 29 in vivo. Particularly, the TGRI value for the P388 model was 93% at the final control timepoint. No mortality was registered among the population up to day 31 of the study. In the HCT116 xenograft model, the compound (170 mg/kg, i.p., o.d., 10 days) provided a T/C ratio close to 60% on day 8 after the treatment was completed. The therapeutic index-estimated as LD50/ED50-for compound 29 in mice was ≥2.5. Molecular docking studies were carried out to predict the possible binding modes of the examined molecules towards MDM2 as the feasible biological target. However, such a mechanism was not confirmed by Western blot data and, apparently, the synthesized compounds have a different mechanism of cytotoxic action.

Low-Dimensional Compounds Containing Bioactive Ligands. Part XX: Crystal Structures, Cytotoxic, Antimicrobial Activities and DNA/BSA Binding of Oligonuclear Zinc Complexes with Halogen Derivatives of 8-Hydroxyquinoline

Two tetranuclear [Zn4Cl2(ClQ)6]·2DMF (1) and [Zn4Cl2(ClQ)6(H2O)2]·4DMF (2), as well as three dinuclear [Zn2(ClQ)3(HClQ)3]I3 (3), [Zn2(dClQ)2(H2O)6(SO4)] (4) and [Zn2(dBrQ)2(H2O)6(SO4)] (5), complexes (HClQ = 5-chloro-8-hydroxyquinoline, HdClQ = 5,7-dichloro-8-hydroxyquinoline and HdBrQ = 5,7-dibromo-8-hydroxyquinoline) were prepared as possible anticancer or antimicrobial agents and characterized by IR spectroscopy, elemental analysis and single crystal X-ray structure analysis. The stability of the complexes in solution was verified by NMR spectroscopy. Antiproliferative activity and selectivity of the prepared complexes were studied using in vitro MTT assay against the HeLa, A549, MCF-7, MDA-MB-231, HCT116 and Caco-2 cancer cell lines and on the Cos-7 non-cancerous cell line. The most sensitive to the tested complexes was Caco-2 cell line. Among the tested complexes, complex 3 showed the highest cytotoxicity against all cell lines. Unfortunately, all complexes showed only poor selectivity to normal cells, except for complex 5, which showed a certain level of selectivity. Antibacterial potential was observed for complex 5 only. Moreover, the DNA/BSA binding potential of complexes 1–3 was investigated by UV-vis and fluorescence spectroscopic methods.

Synthesis and biological evaluation of novel SN38-glucose conjugate for colorectal cancer treatment

7-Ethyl-10-hydroxycamptothecin (SN38), the bioactive metabolite of irinotecan (CPT-11), has been shown to be 100–1000 times more effective than CPT-11. However, the poor water solubility and bioavailability of SN38 constrained its clinical application. In this study, we synthesized a novel SN38-glucose conjugate (FSY04) to address this issue. Our in vitro studies indicated that FSY04 had a potent inhibitory ability against colorectal cancer (CRC) cell lines of SW-480 and HCT-116 compared to the inhibitory capacity of CPT-11. Interestingly, FSY04 possessed lower cytotoxicity against normal cell lines of LO2 and 293T in contrast with CPT-11. Moreover, FSY04 is more active than CPT-11 in inducing apoptosis, inhibiting migration, and invasion. In vivo experiments suggested that half of the equivalent of FSY04 inhibited the growth of SW480 in the xenograft tumor model better than one equivalent of CPT-11. Our data demonstrated FSY04 to be a promising agent in CRC therapy.

Ellagic acid inhibits mitochondrial fission protein Drp-1 and cell proliferation in cancer.

Anthracyclines such as doxorubicin (Dox) are widely used to treat a variety of adult and childhood cancers, however, a major limitation to many of these compounds is their propensity for inducing heart failure. A naturally occurring polyphenolic compound such as Ellagic acid (EA) has been shown by our laboratory to mitigate the cardiotoxic effects of Dox, however, the effects of EA on cancer cell viability have not been established. In this study, we explored the effects of EA alone and in combination with Dox on cancer cell viability and tumorigenesis. Herein, we show that EA induces cell cycle exit and reduces proliferation in colorectal cancer (HCT116) and breast adenocarcinoma cells (MCF7). We show that EA promotes cell cycle exit by a mechanism that inhibits mitochondrial dynamics protein Drp-1. EA treatment of HCT116 and MCF7 cells resulted in a hyperfused mitochondrial morphology that coincided with mitochondrial perturbations including loss of mitochondrial membrane potential, impaired respiratory capacity. Moreover, impaired mitochondrial function was accompanied by a reduction in cell cycle and proliferation markers, CDK1, Ki67, and Cyclin B. This resulted in a reduction in proliferation and widespread death of cancer cells. Furthermore, while Dox treatment alone promoted cell death in both HCT116 and MCF7 cancer cell lines, EA treatment lowered the effective dose of Dox to promote cell death. Hence, the findings of the present study reveal a previously unreported anti-tumor property of EA that impinges on mitochondrial dynamics protein, Drp-1 which is crucial for cell division and tumorigenesis. The ability of EA to lower the therapeutic threshold of Dox for inhibiting cancer cell growth may prove beneficial in reducing cardiotoxicity in cancer patients undergoing anthracycline therapy.

Pyrrolizine/indolizine-bearing (un)substituted isoindole moiety: design, synthesis, antiproliferative and MDR reversal activities, and in silico studies.

Two new series of pyrrolizine/indolizine derivative-bearing (un)substituted isoindole moiety were designed and synthesized. The anticancer potential of the new compounds was evaluated against hepatocellular carcinoma (HepG-2), colorectal carcinoma, colon cancer (HCT-116), and breast cancer (MCF-7) cell lines. Compounds 6d and 6o were the most potent derivatives with IC50 values ranging from 6.02 to 13.87 μM against HePG-2, HCT-116, and MCF-7 cell lines. Moreover, methyl analog of the fluoro-substituted indolizine derivative 6m revealed significant antiproliferative activity against HePG-2, HCT-116, and MCF-7 cancer cell lines with IC50 values of 11.97, 28.37, and 19.87 μM, respectively. The most active anticancer analogs, 6d, 6m, and 6o, were inspected for their putative mechanism of action by estimating their epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK 2) inhibitory activities. Thus, compound 6o displayed the most inhibitory activity against EGFR and CDK 2 with IC50 values of 62 and 118 nM, respectively. Additionally, the quantitative real-time PCR analysis for the P-glycoprotein effect of compounds 6d, 6m, and 6o was performed, in which compound 6o illustrated significant down-regulation of P-gp against the HepG-2 cell line by 0.2732 fold. Mechanistic studies for the most active compounds involving the reversal doxorubicin (DOX) effect of compounds 6d, 6m, and 6o were performed, which illustrated cytotoxic activity with IC50 22.27, 3.88, and 8.79 μM, respectively. Moreover, the apoptotic activity of the most active derivative 6o on HCT-116 cancer cells showed accumulation in the G1 and S phases of the cell cycle.

Cytotoxic Activity of Andrographis lineata Wall. ex Nees: An In Vitro study

The major objective of this investigation was to evaluate the cytotoxic activity of Andrographis lineata Wall. ex Nees var. lawii C.B. Clarke leaf methanol extract on cancer cell lines. In vitro cytotoxicity of Andrographis lineata leaf extract was evaluated against A375 (melanoma), A549 (lung), HCT116 (colon), HeLa (cervix), HepG2 (hepatoma), Jurkat cells (T-cell acute lymphoblastic leukemia), MCF7 (breast cancer), PA1 (ovary), PC3 (prostate) and U87MG (Glioblastoma) cancer cell lines. Andrographis lineata leaf extract showed cytotoxicity activity against all cell lines, however, optimum cytotoxicity was observed against the ovarian cancer cell line (IC50=39.7 μg/ml) cell line. Cell cycle and terminal deoxynucleotidyl transferase dUTP end labeling assays confirmed the cytotoxic activity of Andrographis lineata leaf extract. Reverse phasehigh performance liquid chromatography analysis was performed to recognize the active ingredient in the Andrographis lineata leaf extract and the results reveal that andrographolide was the major component. This investigation is the first report of the anticancer activity of Andrographis lineata leaf extract.

Anti-migration, anti-proliferative, and pro-apoptotic effects on cancer cell line HCT116 using sponge extracts from Lugait, Misamis Oriental, Philippines

Sponge samples coded KL-03P, KL-12P, KL-15P, KL-16P, and KL-18NP collected from Lugait, Misamis Oriental, Philippines were subjected to fractionation resulting in hexane (H), dichloromethane (D), and aqueous (A) fractions of each sponge. They were subsequently subjected to anti-migration, anti-proliferative, and pro-apoptotic activity testing using the Scratch Wound assay, the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay, and the Caspase Glo 3/7 assay, respectively. Fractions KL-03P (D), KL-12P (D), KL-16P H) and KL18NP (D) showed anti-proliferative and pro-apoptotic effects against HCT116 at 30-ppm concentration. Cell shrinkage and noticeable fragmentations indicative of apoptosis were apparent among these fractions based on MTT final snaps. But among these active fractions, the unprecedented abilities of KL-18NP (D) were very notable across assays conducted. This fraction showcased the inhibition of cell migration, which gave a signal for potentially reduced oncogenicity or metastatic capability of HCT116. The negative percentage of wound healing exhibited by this fraction is a manifestation of its cytotoxicity effect. Very remarkably, KL-18NP (D) has a similar degree of responses across the positive controls, respectively. Hence, there is a significant negative relationship between the negative control versus KL-18NP (D) in terms of its anti-migratory and anti-proliferative properties, p&lt;0.05. Additionally, there is a significant positive relationship between the negative control and KL-18NP (D) when it comes to its pro-apoptotic capability, p&lt;0.05. These results make KL-18NP (D) a bioactive hit as an anti-cancer agent source. Confirmatory techniques, structure determination, and target identification methods will further ascertain its mechanism of action as well as the identification of its cellular targets.

사람의 암세포 및 정상세포주에서 구충제로 사용되는 알벤다졸의 세포독성 효과에 관한 연구

The purpose of this study was to examine the cytotoxic effects of albendazole, known as anthelmintic in human cancer (A-549, AGS, MKN-74, SNU 601, HCT-116, MDA-MB-231, MCF-7 and U87-MG) and normal (MRC-5, DSC, USMSC and HEK-293) cell lines derived from various tissues. Following 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the cell growth was highly inhibited below 1 μM albendazole treatment, and the 50% inhibitory concentration (IC50) values were especially lower in the HCT-116, A549 and AGS cancer cell lines, compared with others cell lines. A high incidence of cells with activity of senescence-associated ß-galactosidase was also observed in the albendazole-treated cells. Thus, the albendazole treatment was effectively induced the inhibition of cell growth in both cancer and normal cell lines. Moreover, the cell doubling time was significantly lower in the HCT-116, A549 and AGS cancer cell lines with lower IC50 values, compared with others cell lines. Based on present results, albendazole could serve as a potent chemical/drug for cancer therapy, as its treatment was more available in cell lines with a high cell growth capacity.