APOPTOSIS INDUCTION EFFECT OF CURCUMIN AND ITS ANALOGS PENTAGAMAVUNON-0 AND PENTAGAMAVUNON-1 ON CANCER CELL LINES

ABSTRACTObjectives: This experiment aims to investigate the apoptosis effect of curcumin and its analogs pentagamavunon-0 (PGV-0) and PGV-1 on normaland other cancer cell lines.Methods: Growth inhibition effect was investigated using the MTT method. Double staining used acridine orange, 2-(4-aminodiphenyl)-6-indolcarbamidine dihydrochloride and ethidium bromide was performed to determine morphological changes of cells. Detection of PARP, caspase-3,PUMA and BAX using a western blot method was conducted to elucidate the apoptosis effect of the compounds.Results: PGV-1 (2.5 μM) and PGV-0 (5.0 μM) could inhibit T47D-cell growth on 72 h observation, but not for curcumin. DNA staining showed PGV-1has the strongest apoptosis induction effect on T47D-cells compared to PGV-0 and curcumin as well. Western blot analysis resulted in cleavage PARP(83 kD) on HeLa, T47D, and MCF-7 cells treated with PGV-1 (2.5 μM), PGV-0 (5.0 μM). Curcumin (10.0 μM) just induced apoptosis on T47D-cell andMCF-7 cell, but not HeLa cell. Cleavage PARP resulted by apoptosis process in the cell. PGV-1 (2.5 μM) had a stronger apoptosis effect compared toPGV-0 (5.0 μM) and curcumin (10.0 μM) based on cleaved PARP result qualitatively. On the normal cell (NH3T3), cells that were treated with thecompounds resulted in a negative cleavage PARP. This result indicated that the compounds were part of a selectively induced cancer cell line apoptosisprocess.Conclusion: Curcumin, PGV-0 and PGV-1 could inhibit cell growth by induce apoptosis on cancer cells but not on normal cells, which PGV-1 hasstrongest apoptosis induction effect on cancer cell lines.Keywords: Curcumin and analogs, Apoptosis, Cancer cell lines.

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Synthesis and Characterization of Quinoline-3-Carboxamide Derivatives as Inhibitors of the ATM Kinase

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200731174216 ◽

2020 ◽

Vol 20 (23) ◽

pp. 2070-2079

Author(s):

Srimadhavi Ravi ◽

Sugata Barui ◽

Sivapriya Kirubakaran ◽

Parul Duhan ◽

Kaushik Bhowmik

Keyword(s):

Western Blot ◽

Cancer Cells ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Blot Analysis ◽

Western Blot Analysis ◽

Cancer Cell Lines ◽

Atm Kinase ◽

Cytotoxicity Studies

Background: The importance of inhibiting the kinases of the DDR pathway for radiosensitizing cancer cells is well established. Cancer cells exploit these kinases for their survival, which leads to the development of resistance towards DNA damaging therapeutics. Objective: In this article, the focus is on targeting the key mediator of the DDR pathway, the ATM kinase. A new set of quinoline-3-carboxamides, as potential inhibitors of ATM, is reported. Methods: Quinoline-3-carboxamide derivatives were synthesized and cytotoxicity assay was performed to analyze the effect of molecules on different cancer cell lines like HCT116, MDA-MB-468, and MDA-MB-231. Results: Three of the synthesized compounds showed promising cytotoxicity towards a selected set of cancer cell lines. Western Blot analysis was also performed by pre-treating the cells with quercetin, a known ATM upregulator, by causing DNA double-strand breaks. SAR studies suggested the importance of the electron-donating nature of the R group for the molecule to be toxic. Finally, Western-Blot analysis confirmed the down-regulation of ATM in the cells. Additionally, the PTEN negative cell line, MDA-MB-468, was more sensitive towards the compounds in comparison with the PTEN positive cell line, MDA-MB-231. Cytotoxicity studies against 293T cells showed that the compounds were at least three times less toxic when compared with HCT116. Conclusion: In conclusion, these experiments will lay the groundwork for the evolution of potent and selective ATM inhibitors for the radio- and chemo-sensitization of cancer cells.

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Synthesis, Anticancer Activity on Prostate Cancer Cell Lines and Molecular Modeling Studies of Flurbiprofen-Thioether Derivatives as Potential Target of MetAP (Type II)

Medicinal Chemistry ◽

10.2174/1573406415666190613162322 ◽

2020 ◽

Vol 16 (6) ◽

pp. 735-749 ◽

Cited By ~ 1

Author(s):

Özgür Yılmaz ◽

Burak Bayer ◽

Hatice Bekçi ◽

Abdullahi I. Uba ◽

Ahmet Cumaoğlu ◽

...

Keyword(s):

Prostate Cancer ◽

Molecular Modeling ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Prostate Cancer Cell Lines ◽

Molecular Modeling Studies

Background:: Prostate cancer is still one of the serious causes of mortality and morbidity in men. Despite recent advances in anticancer therapy, there is a still need of novel agents with more efficacy and specificity in the treatment of prostate cancer. Because of its function on angiogenesis and overexpression in the prostate cancer, methionine aminopeptidase-2 (MetAP-2) has been a potential target for novel drug design recently. Objective:: A novel series of Flurbiprofen derivatives N-(substituted)-2-(2-(2-fluoro-[1,1'- biphenyl]-4-il)propanoyl)hydrazinocarbothioamide (3a-c), 4-substituted-3-(1-(2-fluoro-[1,1'-biphenyl]- 4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione (4a-d), 3-(substitutedthio)-4-(substituted-phenyl)- 5-(1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethyl)-4H-1,2,4-triazole (5a-y) were synthesized. The purpose of the research was to evaluate these derivatives against MetAP-2 in vitro and in silico to obtain novel specific and effective anticancer agents against prostate cancer. Methods: The chemical structures and purities of the compounds were defined by spectral methods (1H-NMR, 13C-NMR, HR-MS and FT-IR) and elemental analysis. Anticancer activities of the compounds were evaluated in vitro by using MTS method against PC-3 and DU-143 (androgenindependent human prostate cancer cell lines) and LNCaP (androgen-sensitive human prostate adenocarcinoma) prostate cancer cell lines. Cisplatin was used as a positive sensitivity reference standard. Results:: Compounds 5b and 5u; 3c, 5b and 5y; 4d and 5o showed the most potent biological activity against PC3 cancer cell line (IC50= 27.1 μM, and 5.12 μM, respectively), DU-145 cancer cell line (IC50= 11.55 μM, 6.9 μM and 9.54 μM, respectively) and LNCaP cancer cell line (IC50= 11.45 μM and 26.91 μM, respectively). Some compounds were evaluated for their apoptotic caspases protein expression (EGFR/PI3K/AKT pathway) by Western blot analysis in androgen independent- PC3 cells. BAX, caspase 9, caspsase 3 and anti-apoptotic BcL-2 mRNA levels of some compounds were also investigated. In addition, molecular modeling studies of the compounds on MetAP-2 enzyme active site were evaluated in order to get insight into binding mode and energy. Conclusion:: A series of Flurbiprofen-thioether derivatives were synthesized. This study presented that some of the synthesized compounds have remarkable anticancer and apoptotic activities against prostate cancer cells. Also, molecular modeling studies exhibited that there is a correlation between molecular modeling and anticancer activity results.

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Design, Synthesis, Molecular Docking, and Anticancer Evaluation of Pyrazole Linked Pyrazoline Derivatives with Carbothioamide Tail as EGFR Kinase Inhibitors

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200727093613 ◽

2020 ◽

Vol 21 (1) ◽

pp. 42-60

Author(s):

Farah Nawaz ◽

Ozair Alam ◽

Ahmad Perwez ◽

Moshahid A. Rizvi ◽

Mohd. Javed Naim ◽

...

Keyword(s):

Molecular Docking ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Kinase Assay ◽

Cervix Uteri ◽

Egfr Kinase

Background: The Epidermal Growth Factor Receptor (known as EGFR) induces cell differentiation and proliferation upon activation through the binding of its ligands. Since EGFR is thought to be involved in the development of cancer, the identification of new target inhibitors is the most viable approach, which recently gained momentum as a potential anticancer therapy. Objective: To assess various pyrazole linked pyrazoline derivatives with carbothioamide for EGFR kinase inhibitory as well as anti-proliferative activity against human cancer cell lines viz. A549 (non-small cell lung tumor), MCF-7 (breast cancer cell line), SiHa (cancerous tissues of the cervix uteri), and HCT-116 (colon cancer cell line). Methods: In vitro EGFR kinase assay, in vitro MTT assay, Lactate dehydrogenase release, nuclear staining (DAPI), and flow cytometry cell analysis. Results: Compounds 6h and 6j inhibited EGFR kinase at concentrations of 1.66μM and 1.9μM, respectively. Furthermore, compounds 6h and 6j showed the most potent anti-proliferative results against the A549 KRAS mutation cell line (IC50 = 9.3 & 10.2μM). Through DAPI staining and phase contrast microscopy, it was established that compounds 6h and 6j also induced apoptotic activity in A549 cells. This activity was further confirmed by FACS using Annexin-V-FITC and Propidium Iodide (PI) labeling. Molecular docking studies performed on 6h and 6j suggested that the compounds can bind to the hinge region of ATP binding site of EGFR tyrosine kinase in a similar pose as that of the standard drug gefitinib. Conclusion: The potential anticancer activity of compounds 6h and 6j was confirmed and need further exploration in cancer cell lines of different tissue origin and signaling pathways, as well as in animal models of cancer development.

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Synthesis, Characterization and Biological Evaluation of Metal Adamantyl 2-Pyridylhydrazone Complexes

Molecules ◽

10.3390/molecules25112530 ◽

2020 ◽

Vol 25 (11) ◽

pp. 2530

Author(s):

Ihsan A. Shehadi ◽

Fatima-Azzahra Delmani ◽

Areej M. Jaber ◽

Hana Hammad ◽

Murad A. AlDamen ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Line ◽

Direct Methods ◽

Cancer Cell Lines ◽

Biological Evaluation ◽

Colorectal Cancer Cell Line ◽

Breast Cancer Cell Lines ◽

Human Cancer Cell Lines

Four new complexes derived from adamantly containing hydrazone (APH) ligand with Cu(II) (1), Co(II) (2), Ni(II) (3) and Zn(II) (4), have been synthesized and characterized using different physicochemical methods. The structure of the ligand APH and its copper complex 1 have been established by single-crystal X-ray diffraction direct methods, which reveal that complex 1 has distorted square-pyramidal geometry. Complexes 1–4 are screened against seven human cancer cell lines namely, breast cancer cell lines (MCF7, T47D, MDA-MB-231), prostate cancer cell lines (PC3, DU145) and the colorectal cancer cell line Coco-2, for their antiproliferative activities. Complex 1 has shown a promising anticancer activity compared to the other ones. The structural and spectroscopic analysis of APH and its complexes are confirmed by DFT calculations.

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In vitro chemotherapeutic and antiangiogenic properties of cardenolides from Acokanthera oblongifolia (Hochst.) Codd

Zeitschrift für Naturforschung C ◽

10.1515/znc-2020-0302 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Maha M. Soltan ◽

Howaida I. Abd-Alla ◽

Amal Z. Hassan ◽

Atef G. Hanna

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Enzyme Inactivation ◽

Enzyme Linked Immunosorbent Assay ◽

Anticancer Properties ◽

Mechanistic Investigation ◽

G2m Phase

Abstract Acovenoside A and acobioside A were isolated from Acokanthera oblongifolia. Their anticancer properties were explored regarding, antiproliferative and antiangiogenic activities. The study included screening phase against six cancer cell lines followed by mechanistic investigation against HepG2 cancer cell line. The sulforhodamine-B (SRB) was used to determine their growth inhibitory power. In the other hand, flow cytometry techniques were recorded the cell death type and cell cycle analysis. The clonogenic (colony formation) and wound healing assays, enzyme-linked immunosorbent assay (ELISA) and molecular docking, were performed to evaluate the antiangiogenesis capability. Both compounds were strongly, inhibited four cancer cell lines at GI50 less than 100 nM. The in vitro mechanistic investigation against HepG2 resulted in cell accumulations at G2M phase and induction of apoptosis upon treating cells separately, with 400 nM Acov-A and 200 nM Acob-A. Interestingly, the same concentrations were able to activate caspase-3 by 7.2 and 4.8-fold, respectively. Suppressing the clonogenic capacity of HepG2 cells (20 and 40 nM) and inhibiting the migration of the colon Caco-2 cancer cells were provoke the results of vascular endothelial growth factor receptor2 (VEGFR2) kinase enzyme inactivation. The docked study was highly supportive, to the antiangiogenic approach of both cardenolides. The isolated cardenolides could orchestrate pivotal events in fighting cancer.

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Fusaproliferin, a Fungal Phytotoxin Shows Rapid and Potent Cytotoxicity against Pancreatic Cancer Cell Lines

10.20944/preprints201810.0375.v1 ◽

2018 ◽

Author(s):

Nazia Hoque ◽

Choudhury Mahmood Hasan ◽

Md. Sohel Rana ◽

Amrit Varsha ◽

Md. Hossain Sohrab ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Fusarium Solani ◽

Pancreatic Cancer Cell ◽

Morphological Changes ◽

Cancer Cell Lines ◽

Microscopy Imaging ◽

Ongoing Research ◽

Synthetic Agents

As a part of our ongoing research on endophytic fungi, we have isolated a sesterterpene mycotoxin, fusaproliferin (FUS), from Fusarium solani strain associated with the plant Aglaonema hookerianum Schott. FUS showed rapid and sub-micromolar IC50 against pancreatic cancer cell lines. Time dependent survival analysis and microscopy imaging showed rapid morphological changes in cancer cell lines 4 hours after incubation with FUS. This provides a new chemical scaffold that can be further developed to obtain more potent synthetic agents against pancreatic cancer.

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Evaluation of cytotoxic profile of hydroalcoholic extract of fruit rinds of Garcinia pedunculata on human embryonic kidney and breast carcinoma cells

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20200173 ◽

2020 ◽

Vol 9 (2) ◽

pp. 259

Author(s):

Sukrant Sharma ◽

Ravi Mundugaru ◽

Pradeepa H. Dakappa ◽

Pundalik R. Naik

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Cytotoxic Effect ◽

Metastatic Breast ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Alcoholic Extract ◽

Human Embryonic Kidney ◽

Hek 293

Background: The fruit rinds of Garcinia pedunculata has potential medicinal properties and used in many chronic ailments. It has been demonstrated that cytoprotective effects in various experimental research works. But its cytotoxic effect has not been evaluated. The present study was aimed to screen its relative cytotoxic effect on normal and cancer cell lines.Methods: In the present study, the cytotoxic effect of hydro alcoholic extract of Garcinia pedunculata was evaluated on normal human embryonic kidney (HEK-293) and M.D. Anderson metastatic breast cancer cell lines (MDA-MB 231) using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.Results: Higher dose level of hydro alcoholic extract of Garcinia pedunculata (HAGP) (500 μg/ml) has shown considerable increase (112.503) in the percentage viability of HEK-29 whereas; there is a remarkable decrease in the viable cell population (77.490) in MDA-MB 231.Conclusions: Based on the observed results we could conclude that HAGP has potential cytotoxic effect on the cancer cell line without altering the normal cell growth and proliferation. Thus it has potential to develop as a safer chemotherapeutic agent. Further detailed exploration is required to confirm its therapeutic efficacy in different cancer cell lines.

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Apoptosis Induction, Cell Cycle Arrest and in Vitro Anticancer Activity of Gonothalamin in a Cancer Cell Lines

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2012.13.10.5131 ◽

2012 ◽

Vol 13 (10) ◽

pp. 5131-5136 ◽

Cited By ~ 28

Author(s):

Aied M. Alabsi ◽

Rola Ali ◽

Abdul Manaf Ali ◽

Sami Abdo Radman Al-Dubai ◽

Hazlan Harun ◽

...

Keyword(s):

Cell Cycle ◽

Anticancer Activity ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Apoptosis Induction ◽

Cycle Arrest

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Identification of Prostaglandin F2 Receptor Negative Regulator (PTGFRN) as an internalizable target in cancer cells for antibody-drug conjugate development

PLoS ONE ◽

10.1371/journal.pone.0246197 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0246197

Author(s):

Jorge Marquez ◽

Jianping Dong ◽

Chun Dong ◽

Changsheng Tian ◽

Ginette Serrero

Keyword(s):

Flow Cytometry ◽

Western Blot ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Negative Regulator ◽

Target Validation ◽

Antibody Drug

Antibody-drug conjugates (ADC) are effective antibody-based therapeutics for hematopoietic and lymphoid tumors. However, there is need to identify new targets for ADCs, particularly for solid tumors and cancers with unmet needs. From a hybridoma library developed against cancer cells, we selected the mouse monoclonal antibody 33B7, which was able to bind to, and internalize, cancer cell lines. This antibody was used for identification of the target by immunoprecipitation and mass spectrometric analysis, followed by target validation. After target validation, 33B7 binding and target positivity were tested by flow cytometry and western blot analysis in several cancer cell lines. The ability of 33B7 conjugated to saporin to inhibit in vitro proliferation of PTFRN positive cell lines was investigated, as well as the 33B7 ADC in vivo effect on tumor growth in athymic mice. All flow cytometry and in vitro internalization assays were analyzed for statistical significance using a Welsh’s T-test. Animal studies were analyzed using Two-Way Analysis of Variance (ANOVA) utilizing post-hoc Bonferroni analysis, and/or Mixed Effects analysis. The 33B7 cell surface target was identified as Prostaglandin F2 Receptor Negative Regulator (PTGFRN), a transmembrane protein in the Tetraspanin family. This target was confirmed by showing that PTGFRN-expressing cells bound and internalized 33B7, compared to PTGFRN negative cells. Cells able to bind 33B7 were PTGFRN-positive by Western blot analysis. In vitro treatment PTGFRN-positive cancer cell lines with the 33B7-saporin ADC inhibited their proliferation in a dose-dependent fashion. 33B7 conjugated to saporin was also able to block tumor growth in vivo in mouse xenografts when compared to a control ADC. These findings show that screening antibody libraries for internalizing antibodies in cancer cell lines is a good approach to identify new cancer targets for ADC development. These results suggest PTGFRN is a possible therapeutic target via antibody-based approach for certain cancers.

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