Cytotoxic Action of N-aryl, Furan-derived Aminophosphonates against HT29 and HCT116 Cancer Cell Lines

Background: The anticancer activity of aminophosphonic derivatives has been described extensively, some recent papers included furan-derived aminophosphonates and their cytostatic action against various cancer cells. Objective: A series of twelve furan-derived dibenzyl and diphenyl aminophosphonates 2a-f and 3a-f was synthesized and tested in aspect of their cytotoxic action on two cell lines of colorectal cancer: HT29 and HCT116. Seven of them are new compounds, while the rest five have already been published by us, together with their cytotoxic action against squamous esophageal cancer cells. Methods: To estimate the cytotoxicity effect of tested compounds MTT test was used. Pro-apoptotic activity of five selected compounds was evaluated using APC Annexin V Apoptosis Detection Kit on a flow cytometer. Quantification of caspases 3/7 activity was performed using Caspase-Glo® 3/7 Assay Kit. Results: Five of these aminophosphonates showed significant cytotoxicity higher than those of cisplatin. Simultaneous evaluation of their cytotoxicity against PBLs revealed that these compounds are rather not harmful for regular human lymphocytes. Tests on apoptosis vs. their necrotic actions on cells were performed with selected compounds showing the most significant cytotoxicity against cancer cells and all tested compounds did not induce significant increase of necrosis in cells, whereas they showed moderate-to-strong proapoptotic actions even at the lowest applied concentration. Caspase 3/7 activity results confirmed proapoptotic properties of tested aminophosphonates. Conclusion: From among studied compounds, dibenzyl N-phenyl substituted amino(2-furyl)methylphsophonates were found to be more potent compounds in aspect of their antiproliferative action than the corresponding diphenyl derivatives.

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Pyrrolizines as Potential Anticancer Agents: Design, Synthesis, Caspase-3 activation and Micronucleus (MN) Induction

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180409155520 ◽

2019 ◽

Vol 18 (15) ◽

pp. 2124-2130

Author(s):

Amany Belal

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Anticancer Agents ◽

Caspase 3 ◽

Assay Method ◽

Breast Adenocarcinoma ◽

Compound I ◽

Design Synthesis ◽

Ic50 Values ◽

New Compounds

Background: For further exploration of the promising pyrrolizine scaffold and in continuation of our previous work, that proved the potential anticancer activity of the hit compound I, a new series of pyrrolizines 2-5 and 7-9 were designed and synthesized. Methods: Structures of the new compounds were confirmed by IR, 1H-NMR, 13C-NMR and elemental analysis. Antitumor activity for the prepared compounds against human breast adenocarcinoma (MCF-7), liver (HEPG2) and colon (HCT116) cancer cell lines was evaluated using SRB assay method. Result: Compounds 2, 3 and 5 were the most potent on colon cancer cells, their IC50 values were less than 5 µM. Compounds 2, 3 and 8 were the most potent on liver cancer cells, their IC50 values were less than 10 µM. As for MCF7, compounds 2, 7, 8 and 9 were the most active with IC50 values less than 10 µM. We can conclude that combining pyrrolizine scaffold with urea gave abroad spectrum anticancer agent 2 against the three tested cell lines. Micronucleus assays showed that compounds 2, 3, 8 are mutagenic and can induce apoptosis. In addition, caspase-3 activation was evaluated and compound 2 showed increase in the level of caspase-3 (9 folds) followed by 3 (8.28 folds) then 8 (7.89 folds). Conclusion: The obtained results encourage considering these three compounds as novel anticancer prototypes.

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C5-curcuminoid-dithiocarbamate based molecular hybrids: synthesis and anti-inflammatory and anti-cancer activity evaluation

RSC Advances ◽

10.1039/c4ra03655g ◽

2014 ◽

Vol 4 (54) ◽

pp. 28756-28764 ◽

Cited By ~ 9

Author(s):

Amit Anthwal ◽

Kundan Singh ◽

M. S. M. Rawat ◽

Amit K. Tyagi ◽

Bharat B. Aggarwal ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Activity Evaluation ◽

Anti Cancer ◽

Molecular Hybrids ◽

Anti Inflammatory ◽

New Compounds ◽

Cancer Activity ◽

Proliferation Potential

The C5-curcumin-dithiocarbamate analogues were synthesized in search of new molecules with anti-proliferation potential against cancer cells. These new compounds demonstrated higher anti-proliferation and anti-inflammatory activity against cancer cell lines in comparison to curcumin.

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Comparison of the effect of rhodium citrate-associated iron oxide nanoparticles on metastatic and non-metastatic breast cancer cells

Cancer Nanotechnology ◽

10.1186/s12645-019-0052-1 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Natalia Lemos Chaves ◽

Danilo Aquino Amorim ◽

Cláudio Afonso Pinho Lopes ◽

Irina Estrela-Lopis ◽

Julia Böttner ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Breast Cancer Cells ◽

Human Tumor ◽

Metastatic Breast ◽

Cytotoxic Action ◽

Dependent Manner ◽

Metastatic Cells ◽

Mcf 7

Abstract Background Nanocarriers have the potential to improve the therapeutic index of currently available drugs by increasing drug efficacy, lowering drug toxicity and achieving steady-state therapeutic levels of drugs over an extended period. The association of maghemite nanoparticles (NPs) with rhodium citrate (forming the complex hereafter referred to as MRC) has the potential to increase the specificity of the cytotoxic action of the latter compound, since this nanocomposite can be guided or transported to a target by the use of an external magnetic field. However, the behavior of these nanoparticles for an extended time of exposure to breast cancer cells has not yet been explored, and nor has MRC cytotoxicity comparison in different cell lines been performed until now. In this work, the effects of MRC NPs on these cells were analyzed for up to 72 h of exposure, and we focused on comparing NPs’ therapeutic effectiveness in different cell lines to elect the most responsive model, while elucidating the underlying action mechanism. Results MRC complexes exhibited broad cytotoxicity on human tumor cells, mainly in the first 24 h. However, while MRC induced cytotoxicity in MDA-MB-231 in a time-dependent manner, progressively decreasing the required dose for significant reduction in cell viability at 48 and 72 h, MCF-7 appears to recover its viability after 48 h of exposure. The recovery of MCF-7 is possibly explained by a resistance mechanism mediated by PGP (P-glycoprotein) proteins, which increase in these cells after MRC treatment. Remaining viable tumor metastatic cells had the migration capacity reduced after treatment with MRC (24 h). Moreover, MRC treatment induced S phase arrest of the cell cycle. Conclusion MRC act at the nucleus, inhibiting DNA synthesis and proliferation and inducing cell death. These effects were verified in both tumor lines, but MDA-MB-231 cells seem to be more responsive to the effects of NPs. In addition, NPs may also disrupt the metastatic activity of remaining cells, by reducing their migratory capacity. Our results suggest that MRC nanoparticles are a promising nanomaterial that can provide a convenient route for tumor targeting and treatment, mainly in metastatic cells.

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Epigenetic modulation combined with PD-1/PD-L1 blockade enhances immunotherapy based on MAGE-A11 antigen-specific CD8+T cells against esophageal carcinoma

Carcinogenesis ◽

10.1093/carcin/bgaa057 ◽

2020 ◽

Vol 41 (7) ◽

pp. 894-903

Author(s):

Yunyan Wu ◽

Meixiang Sang ◽

Fei Liu ◽

Jiandong Zhang ◽

Weijing Li ◽

...

Keyword(s):

T Cells ◽

Esophageal Cancer ◽

Tumor Cell ◽

Cancer Cells ◽

Cell Lines ◽

Cd8 T Cells ◽

Dna Methyltransferase ◽

Tumor Cell Lines ◽

Epigenetic Modulation ◽

Esophageal Cancer Cells

Abstract Cancer testis antigens (CTAs) are promising targets for T cell-based immunotherapy and studies have shown that certain CT genes are epigenetically depressed in cancer cells through DNA demethylation. Melanoma-associated antigen A11 (MAGE-A11) is a CTA that is frequently expressed in esophageal cancer and is correlated with a poor esophageal cancer prognosis. Consequently, MAGE-A11 is a potential immunotherapy target. In this study, we evaluated MAGE-A11 expression in esophageal cancer cells and found that it was downregulated in several tumor cell lines, which restricted the effect of immunotherapy. Additionally, the specific recognition and lytic potential of cytotoxic T lymphocytes (CTLs) derived from the MAGE-A11 was determined. Specific CTLs could kill esophageal cancer cells expressing MAGE-A11 but rarely lysed MAGE-A11-negative tumor cells. Therefore, induction of MAGE-A11 expression is critical for CTLs recognition and lysis of esophageal cancer cells. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine increased MAGE-A11 expression in esophageal cancer cells and subsequently enhanced the cytotoxicity of MAGE-A11-specific CD8+T cells against cancer cell lines. Furthermore, we found that PD-L1 expression in esophageal cancer cells affected the antitumor function of CTLs. programmed death-1 (PD-1)/PD-L1 blockade could increase the specific CTL-induced lysis of HLA-A2+/MAGE-A11+ tumor cell lines treated with 5-aza-2′-deoxycytidine. These findings indicate that the treatment of tumor cells with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine augments MAGE-A11 expression in esophageal cancer cells. The combination of epigenetic modulation by 5-aza-2′-deoxycytidine and PD-1/PD-L1 blockade may be useful for T cell-based immunotherapy against esophageal cancer.

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Anticancer Potential of Fruit Extracts from Vatica diospyroides Symington Type SS and Their Effect on Program Cell Death of Cervical Cancer Cell Lines

The Scientific World JOURNAL ◽

10.1155/2019/5491904 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Atchara Chothiphirat ◽

Kesara Nittayaboon ◽

Kanyanatt Kanokwiroon ◽

Theera Srisawat ◽

Raphatphorn Navakanitworakul

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Morphological Changes ◽

Annexin V ◽

Siha Cell ◽

Caspase 8 ◽

Dependent Manner ◽

Cervical Cancer Cells ◽

Dose Dependent

Vatica diospyroides Symington is locally known as Chan-Ka-Pho in Thailand. Ancient people have used it as therapeutic plant for cardiac and blood tonic cure. The purpose of this study was to investigate the potential cytotoxicity and selectivity of the extracts from V. diospyroides type SS fruit on cervical cancer HeLa and SiHa cell lines and to examine its underlying mechanism of action. MTT assay revealed that the extracts showed inhibition of cell survival in a dose-dependent manner and exhibited highly cytotoxic activity against both HeLa and SiHa cells with IC50 value less than 20 μg/mL along with less toxicity against L929 cells. Acetone cotyledon extract (ACE) showed the best selectivity index value of 4.47 (HeLa) and 3.51 (SiHa). Distinctive morphological changes were observed in ACE-treated cervical cancer cells contributing to apoptosis action. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that ACE induced apoptosis in HeLa and SiHa cell lines in a dose-dependent manner. Treatment of ACE with half IC50 caused DNA fragmentation and also activated increasing of bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure. The results suggest that ACE has potent and selective cytotoxic effect against cervical cancer cells and the potential to induce bax and caspase-8-dependent apoptosis. Hence, the ACE could be further exploited as a potential lead in cancer treatment.

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Chitosan Coated Microparticles Enhance Simvastatin Colon Targeting and Pro-Apoptotic Activity

Marine Drugs ◽

10.3390/md18040226 ◽

2020 ◽

Vol 18 (4) ◽

pp. 226 ◽

Cited By ~ 5

Author(s):

Nabil A. Alhakamy ◽

Usama A. Fahmy ◽

Osama A. A. Ahmed ◽

Giuseppe Caruso ◽

Filippo Caraci ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Annexin V ◽

Entrapment Efficiency ◽

Cell Fraction ◽

Colon Cancer Cells ◽

Colon Targeting ◽

Eudragit S100 ◽

Hct 116 ◽

Apoptotic Activity

This work aimed at improving the targeting and cytotoxicity of simvastatin (SMV) against colon cancer cells. SMV was encapsulated in chitosan polymers, followed by eudragit S100 microparticles. The release of SMV double coated microparticles was dependent on time and pH. At pH 7.4 maximum release was observed for 6 h. The efficiency of the double coat to target colonic tissues was confirmed using real-time X-ray radiography of iohexol dye. Entrapment efficiency and particle size were used in the characterization of the formula. Cytotoxicity of SMV microparticles against HCT-116 colon cancer cells was significantly improved as compared to raw SMV. Cell cycle analysis by flow cytomeric technique indicated enhanced accumulation of colon cancer cells in the G2/M phase. Additionally, a significantly higher cell fraction was observed in the pre-G phase, which highlighted enhancement of the proapoptotic activity of SMV prepared in the double coat formula. Assessment of annexin V staining was used for confirmation. Cell fraction in early, late and total cell death were significantly elevated. This was accompanied by a significant elevation of cellular caspase 3 activity. In conclusion, SMV-loaded chitosan coated with eudragit S100 formula exhibited improved colon targeting and enhanced cytotoxicity and proapoptotic activity against HCT-116 colon cancer cells.

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In-Vitro Anti-Proliferative, Apoptotic and Antioxidative Activities of Medicinal Herb Kalonji (Nigella sativa)

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190821144633 ◽

2019 ◽

Vol 20 (15) ◽

pp. 1288-1308

Author(s):

Tahir Maqbool ◽

Sana J. Awan ◽

Sabeen Malik ◽

Faheem Hadi ◽

Somia Shehzadi ◽

...

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Internal Control ◽

Nigella Sativa ◽

Annexin V ◽

Cancer Cell Lines ◽

Oxidative Enzymes

Background: Natural product with apoptotic activity could serve as a potential new source for anti-cancer medicine. Numerous phytochemicals from plants have shown to exert antineoplastic effects via programmed cell death (apoptosis). Cancer is one of the leading causes of death in prosperous countries. The subject study was intended to evaluate the anticancer properties of Kalonji extracts against cancer cell lines HeLa and HepG2 and normal cell lines BHK and VERO were used as normal controls. Materials & Methods: For the evaluation of anti-proliferative effects, cell viability and cell death in all groups of cells were evaluated via MTT, crystal violet and trypan blue assays. For the evaluation of angiogenesis, Immunocytochemistry and ELISA of VEGF were done. Immunocytochemistry and ELISA of Annexin-V and p53 were performed for the estimation of apoptosis in all groups of cells. Furthermore, LDH assay, antioxidant enzymes activity (GSH, APOX, CAT and SOD) and RT-PCR with proliferative and apoptotic markers along with internal control were also performed. Cancer cells of both cell lines HepG2 and HeLa cells showed reduced viability, angiogenesis and proliferation with increased apoptosis when treated with Kalonji extracts. Whereas anti-oxidative enzymes show enhanced levels in treated cancer cells as compared to untreated ones. Conclusion: It was observed that Kalonji extracts have the ability to induce apoptosis and improve the antioxidant status of HeLa and HepG2 cells. They can also inhibit the proliferation and angiogenesis in both these cancer cell lines.

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Oncolytic adenovirus expressing apoptotic genes targets radiation resistant (RR) esophageal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21043 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21043-21043

Author(s):

J. Y. Chang ◽

R. Komaki ◽

X. Zhang ◽

L. Wang ◽

B. Fang

Keyword(s):

Gene Expression ◽

Esophageal Cancer ◽

Radiation Exposure ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Esophageal Cancer Cell ◽

Esophageal Cancer Cells ◽

Trans Gene ◽

Fractionated Radiation

21043 Background: Only 25% of esophageal cancer patients achieve pathological complete response after standard chemoradiotherapy. Radiation dose escalation is associated with higher toxicity but no therapeutic improvement. In addition, esophageal cancer cells may develop radiation resistance (RR) after fractionated radiation exposure. Therefore, molecular targeting therapy for RR esophageal cancer is urgently needed. Methods: Six pairs of RR esophageal cancer cell lines were established by applying continuous 2 Gy fractionated irradiation. Ad/TRAIL-E1, an oncolytic adenoviral vector expressing both apoptotic TRAIL and viral E1A genes under the control of tumor specific human telomerase reverse transcriptase promoter, was constructed. Phosphate buffer solution and vectors expressing the TRAIL gene only, the GFP marker protein only, or the E1A gene only served as controls. Trans-gene expression, apoptosis activation, and the RR esophageal cancer cells targeted were evaluated in vitro and in vivo. A human esophageal RR cancer model was established and locally treated with Ad/TRAIL-E1 or controls. Results: After fractionated radiation exposure, esophageal cancer cell lines developed RR (up to 25-fold) that was associated with activation of the anti-apoptotic pathway. Ad/TRAIL-E1 activated an apoptotic cascade of caspases and selectively killed esophageal cancer cells but not normal cells. Ad/TRAIL-E1 preferentially targeted RR stem-like cancer cells with higher trans-gene expression and cell killing compared with parental cells. Overexpression (3 times) of Coxsackie's and adenoviral receptors in RR esophageal cancer cells compared with parental cells was noted. Ad/TRAIL-E1 therapy resulted in 40% tumor-free survival without the treatment- related toxicity found in human RR esophageal adenocarcinoma mouse models (p<0.05 as compared with controls). Conclusions: Esophageal cancer cells develop RR after fractionated radiation exposure. Ad/TRAIL-E1 preferentially targeted RR stem-like esophageal cancer cells, which resulted in a 40% cure rate. No significant financial relationships to disclose.

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Screening Antitumor Compounds Psoralen and Isopsoralen fromPsoralea corylifoliaL. Seeds

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nen087 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 54

Author(s):

Yi Wang ◽

Chengtao Hong ◽

Chenguang Zhou ◽

Dongmei Xu ◽

Hai-bin Qu

Keyword(s):

Anticancer Activity ◽

Cancer Cells ◽

Annexin V ◽

Volatile Fraction ◽

Dependent Manner ◽

Psoralea Corylifolia ◽

Medical Plant ◽

Apoptotic Activity ◽

Fraction I ◽

Dose Dependent

Psoralea corylifoliaL. (Fabaceae) is a widely used medical plant in China. This study was designed to screen and identify bioactive compounds with anticancer activity from the seeds ofPsoralea corylifoliaL. One volatile fraction (fraction I) and three other fractions (fraction II, III, IV) from methanol extraction ofP. corylifoliaL. were obtained. Bioactivities of these fractions were evaluated by the cytotoxicity on KB, KBv200, K562, K562/ADM cancer cells with MTT assay. Major components in the active fraction were identified by HPLC/MSn. Fraction IV significantly inhibits the growth of cancer cells in a dose-dependent manner. The IC50values were 21.6, 24.4, 10.0 and 26.9, respectively. Psoralen and isopsoralen, isolated from fraction IV, were subject to bioactive assay and presented a dose-dependent anticancer activity in four cancer cell lines (KB, KBv200, K562 and K562/ADM). The IC50values of psoralen were 88.1, 86.6, 24.4 and 62.6, which of isopsoralen were 61.9, 49.4, 49.6 and 72.0, respectively. Apoptosis of tumor cell significantly increased after treated with psoralen and isopsoralen. Induction of apoptotic activity was confirmed by flow cytometry after staining with Annexin V/PI. These results suggested psoralen and isopsoralen contribute to anticancer effect ofP. corylifoliaL.

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Induction of Apoptotic Effects of Antiproliferative Protein from the Seeds ofBorreria hispidaon Lung Cancer (A549) and Cervical Cancer (HeLa) Cell Lines

BioMed Research International ◽

10.1155/2014/179836 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

S. Rupachandra ◽

D. V. L. Sarada

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Protein Fraction ◽

Gel Filtration ◽

Apparent Molecular Weight ◽

Peptide Mass Fingerprinting ◽

Dependent Manner ◽

Peptide Mass ◽

Hela Cell Lines ◽

Apoptotic Activity

A 35 KDa protein referred to as F3 was purified from the seeds ofBorreria hispidaby precipitation with 80% ammonium sulphate and gel filtration on Sephadex G-100 column. RP-HPLC analysis of protein fraction (F3) on an analytical C-18 column produced a single peak, detected at 220 nm. F3 showed an apparent molecular weight of 35 KDa by SDS PAGE and MALDI-TOF-MS analyses. Peptide mass fingerprinting analysis of F3 showed the closest homology with the sequence of 1-aminocyclopropane-1-carboxylate deaminase ofPyrococcus horikoshii. The protein (F3) exhibited significant cytotoxic activity against lung (A549) and cervical (HeLa) cancer cells in a dose-dependent manner at concentrations ranging from 10 µg to 1000 µg/mL, as revealed by the MTT assay. Cell cycle analysis revealed the increased growth of sub-G0 population in both cell lines exposed to a concentration of 1000 µg/mL of protein fraction F3 as examined from flow cytometry. This is the first report of a protein from the seeds ofBorreria hispidawith antiproliferative and apoptotic activity in lung (A549) and cervical (HeLa) cancer cells.

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