Preparation of Curcumin-Containing α-, β-, and γ-Cyclodextrin/Polyethyleneglycol-Conjugated Gold Multifunctional Nanoparticles and Their <i>in Vitro</i> Cytotoxic Effects on A549 Cells

Background: More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. Objective: This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. Materials and Methods: DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. Conclusion: The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals.

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Anti-Metastatic Effects of Lupeol via the Inhibition of MAPK/ERK Pathway in Lung Cancer

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200424131548 ◽

2020 ◽

Vol 21 (2) ◽

pp. 201-206 ◽

Cited By ~ 2

Author(s):

Mital Bhatt ◽

Mitesh Patel ◽

Mohd Adnan ◽

Mandadi N. Reddy

Keyword(s):

Lung Cancer ◽

Cell Migration ◽

Cancer Metastasis ◽

A549 Cells ◽

Cancer Therapeutics ◽

Enzyme Linked Immunosorbent Assay ◽

Erk Pathway ◽

Cytotoxic Effects ◽

Lung Cancer Metastasis

Background and Objective: ERK pathway is one of the most crucial pathways in lung cancer metastasis. Targeting its pathway is decisive in lung cancer research. Thus, this study demonstrated for the first time a significant and selective anti-metastatic effects of lupeol against lung cancer A549 cells via perturbations in the ERK signaling pathway. Materials and Methods: Human protein targets of lupeol were predicted in silico. Migration and cytotoxicity assays were carried out in vitro. Expression levels of proteins Erk1/2 and pErk1/2 were ensured using Enzyme-Linked Immunosorbent Assay (ELISA). Semi-quantitative RT-PCR technique was used to estimate changes in crucial mesenchymal marker geneexpression levels of Ncadherin and vimentin. Results: Lupeol was found to target ERK and MEK proteins effectively. Despite having no cytotoxic effects, lupeol also significantly inhibited cell migration in A549 cells with decreased expression of the pErk1/2 protein along with N-cadherin and vimentin genes. Conclusion: Lupeol inhibits cell migration, showed no cytotoxic effects on A549 cells, decreased pErk1/2 and EMT gene expression. Thus, it can serve as a potential ERK pathway inhibitor in lung cancer therapeutics.

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Cytotoxic effects of disulfiram and synergism with cisplatin on ovarian cancer cells in vitro

10.1055/s-0038-1671352 ◽

2018 ◽

Author(s):

F Guo ◽

Z Yang ◽

J Xu ◽

J Sehouli ◽

AE Albers ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Cytotoxic Effects

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Synthesis and Anti-Tumor Activity Evaluation of Novel 7-Fluoro-4-(1- Piperazinyl) Quinolines

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180820131036 ◽

2019 ◽

Vol 16 (6) ◽

pp. 663-669

Author(s):

Dan Liu ◽

Aiqi Xue ◽

Zhixin Liu ◽

Yi Zhang ◽

Penghui Peng ◽

...

Keyword(s):

Spectral Analysis ◽

Cancer Therapy ◽

Carcinoma Cell ◽

A549 Cells ◽

Quinoline Derivatives ◽

Human Carcinoma ◽

Carcinoma Cell Lines ◽

Human Carcinoma Cell ◽

Anti Tumor Activity

Background: Three series of new 7-fluoro-4-(1-piperazinyl) quinolines (I1~I6, II1~II2 and IV1~IV4) were synthesized. Their anti-tumor activity was evaluated in vitro against three human carcinoma cell lines, namely SGC-7901 cells, BEL-7402 cells and A549 cells expressing high levels of EGFR by Methyl Thiazolyl Terazolium (MTT) assay. Methods: Three series of quinoline derivatives were synthesized, characterized and evaluated for their in vitro anti-tumor activities. Results and Discussion: Structures of the newly synthesized compounds were confirmed by spectral analysis. The preliminary bioassay indicated that compounds I1, I10 and II1 exhibited better anti-tumor activity than the rest of the target compounds and gefitinib against A549 cell based assay, which demonstrated that compounds I1, I10 and II1 are potential agents for cancer therapy. Results suggested that the substitutes on piperazinyl influenced anti-tumor activities remarkably. Conclusion: These results are useful for discovering more potent novel anti-tumor compounds and further studies are ongoing.

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Nano-Curcumin Regulates p53 Phosphorylation and PAI-1 Expression during Bleomycin Induced Injury in Alveolar Basal Epithelial Cells

Current Bioactive Compounds ◽

10.2174/1573407214666180727093612 ◽

2020 ◽

Vol 16 (1) ◽

pp. 85-89

Author(s):

Mahesh M. Gouda ◽

Ashwini Prabhu ◽

Varsha Reddy S.V. ◽

Rafa Jahan ◽

Yashodhar P. Bhandary

Keyword(s):

Epithelial Cells ◽

Lung Injury ◽

Molecular Mechanisms ◽

A549 Cells ◽

Plasminogen Activator Inhibitor ◽

Underlying Mechanism ◽

Protective Role ◽

Alveolar Epithelial Cells ◽

Cellular Damage

Background: Bleomycin (BLM) is known to cause DNA damage in the Alveolar Epithelial Cells (AECs). It is reported that BLM is involved in the up-regulation of inflammatory molecules such as neutrophils, macrophages, chemokines and cytokines. The complex underlying mechanism for inflammation mediated progression of lung injury is still unclear. This investigation was designed to understand the molecular mechanisms associated with p53 mediated modulation of Plasminogen Activator Inhibitor-I (PAI-I) expression and its regulation by nano-curcumin formulation. Methods: A549 cells were treated with BLM to cause the cellular damage in vitro and commercially available nano-curcumin formulation was used as an intervention. Cytotoxic effect of nano-curcumin was analyzed using Methyl Thiazolyl Tetrazolium (MTT) assay. Protein expressions were analyzed using western blot to evaluate the p53 mediated changes in PAI-I expression. Results: Nano-curcumin showed cytotoxicity up to 88.5 % at a concentration of 20 μg/ml after 48 h of treatment. BLM exposure to the cells activated the phosphorylation of p53, which in turn increased PAII expression. Nano-curcumin treatment showed a protective role against phosphorylation of p53 and PAI-I expression, which in turn regulated the fibro-proliferative phase of injury induced by bleomycin. Conclusion: Nano-curcumin could be used as an effective intervention to regulate the severity of lung injury, apoptosis of AECs and fibro-proliferation during pulmonary injury.

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Benzisothiazolone Derivatives Exhibit Cytotoxicity in Hodgkin’s Lymphoma Cells through NF-κB Inhibition and are Synergistic with Doxorubicin and Etoposide

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200213103513 ◽

2020 ◽

Vol 20 (6) ◽

pp. 715-723

Author(s):

Natarajan Nandakumar ◽

Pushparathinam Gopinath ◽

Jacob Gopas ◽

Kannoth M. Muraleedharan

Keyword(s):

Synergistic Effect ◽

Hodgkin’S Lymphoma ◽

A549 Cells ◽

Hodgkin's Lymphoma ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Lymphoma Cells ◽

Nuclear Extracts ◽

Gene Assay

Background: The authors investigated the NF-κB inhibitory role of three Benzisothiazolone (BIT) derivatives (1, 2 and 3) in Hodgkin’s Lymphoma cells (L428) which constitutively express activated NF-κB. All three compounds showed dose-dependent NF-κB inhibition (78.3, 70.7 and 34.6%) in the luciferase reporter gene assay and were found cytotoxic at IC50 values of 3.3μg/ml, 4.35μg/ml and 13.8μg/ml, respectively by the XTT assay. BIT 1and BIT 2 (but not BIT 3) suppressed both NF-κB subunits p50 and p65 in cytoplasmic and nuclear extracts in a concentration-dependent manner. Furthermore, BIT 1 showed a moderate synergistic effect with the standard chemotherapy drugs etoposide and doxorubicin, whereas BIT 2 and 3 showed a moderate additive effect to antagonistic effect. Cisplatin exhibited an antagonist effect on all the compounds tested under various concentrations, except in the case of 1.56μg/ml of BIT 3 with 0.156μg/ml of cisplatin. The compounds also inhibited the migration of adherent human lung adenocarcinoma cells (A549) in vitro. We conclude that especially BIT 1 and BIT 2 have in vitro anti-inflammatory and anti-cancer activities, which can be further investigated for future potential therapeutic use. Methods: Inspired by the electrophilic sulfur in Nuphar alkaloids, monomeric and dimeric benzisothiazolones were synthesized from dithiodibenzoic acid and their NF-κB inhibitory role was explored. NF-κB inhibition and cytotoxicity of the synthesized derivatives were studied using luciferase reporter gene assay and XTTassay. Immunocytochemistry studies were performed using L428 cells. Cell migration assay was conducted using the A549 cell line. L428 cells were used to conduct combination studies and the results were plotted using CompuSyn software. Results: Benzisothiazolone derivatives exhibited cytotoxicity in Hodgkin’s Lymphoma cells through NF-κB inhibition. Potent compounds showed suppression of both NF-κB subunits p50 and p65 in a concentrationdependent manner, both in cytoplasmic and nuclear extracts. Combination studies suggest that benzisothiazolone derivatives possess a synergistic effect with etoposide and doxorubicin. Furthermore, the compounds also inhibited the migration of A549 cells. Conclusion: Benzisothiazolones bearing one or two electrophilic sulfur atoms as part of the heterocyclic framework exhibited cytotoxicity in Hodgkin’s Lymphoma cells through NF-κB inhibition. In addition, these derivatives also exhibited a synergistic effect with etoposide and doxorubicin along with the ability to inhibit the migration of A549 cells. Our study suggests that BIT-based new chemical entities could lead to potential anticancer agents.

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In Vitro Evaluation of Chitosan Induced Cytotoxicity against Cancerous Cell lines: MCF-7, Saos-2 and HeLa

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190507113949 ◽

2019 ◽

Vol 19 ◽

Author(s):

Zeinab Abedian ◽

Niloofar Jenabian ◽

Ali Akbar Moghadamnia ◽

Ebrahim Zabihi ◽

Roghayeh Pourbagher ◽

...

Keyword(s):

Flow Cytometry ◽

Cell Lines ◽

Anticancer Agents ◽

Fibroblast Cells ◽

Apoptosis Induction ◽

Cytotoxic Effects ◽

Cancerous Cell ◽

Significant Concentration ◽

Mcf 7

Objective/ Background: Cancer is still the most common cause of morbidity in world and new powerful anticancer agents without severe side effects from natural sources is important. Methods: The evaluation of cytotoxicity and apoptosis induction was carried out in MCF-7,HeLa and Saos-2 as cancerous cell lines with different histological origin and human fibroblast served as control normal cell. The cells were treated with different concentrations of chitosan and the cytotoxicity was determined using MTT assay after 24, 48 and 72 h .The mode of death was evaluated by flow cytometry . Results: While both types of chitosan showed significant concentration-dependently cytotoxic effects against the three cancerous cell lines, fibroblast cells showed somehow more compatibility with chitosan. On the other hand, there were no significant differences between LMWC and HMWC cytotoxicity in all cell lines. The flow cytometry results showed the apoptosis pattern of death more in Saos-2 and HeLa while necrosis was more observable with MCF7. Also higher viability with both types of chitosan was seen in fibroblast as normal cells Conclusion: Chitosan shows anticancerous effect against 3 cancerous cell lines, while it is compatible with normal diploid fibroblast cells. Furthermore, it seems that the molecular weight of chitosan does not affect its anticancerous property.

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Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200302114550 ◽

2020 ◽

Vol 20 (10) ◽

pp. 1241-1249

Author(s):

Hong-Chuan Liu ◽

Li-Ming Qiao ◽

Wei Zheng ◽

Zhao-Bao Xiang ◽

Hai-Sheng Chen ◽

...

Keyword(s):

Acute Toxicity ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Folk Medicine ◽

A549 Cells ◽

Cancer Cell Lines ◽

Human Cancer Cell Lines ◽

Derivatives Of

Background: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure- Activity Relations (SAR) of this compound have not yet been reported. Objective: The aim of this study was to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. Methods: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. Results: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds showed potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presented the greatest cytotoxicity, with IC50 values of 0.26μM and 1.10μM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induced weak apoptosis of A549 cells but showed great potential in stimulating the apoptosis of HL- 60 cells. Acute toxicity assays indicated that compound 17 is relatively safer. Conclusion: The results reported herein indicate that the synthesized GLA derivatives exhibited greater cytotoxicity against leukemia cells than against other types of tumors. In particular, 7,14-diacylation product of GLA was found to be an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

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VDAC1 Mediated Anticancer Activity of Gallic Acid in Human Lung Adenocarcinoma A549 Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170912115441 ◽

2018 ◽

Vol 18 (2) ◽

pp. 255-262 ◽

Cited By ~ 5

Author(s):

Aikebaier Maimaiti ◽

Amier Aili ◽

Hureshitanmu Kuerban ◽

Xuejun Li

Keyword(s):

Western Blot ◽

Cell Viability ◽

Gallic Acid ◽

Molecular Mechanisms ◽

A549 Cells ◽

Dependent Manner ◽

Lung Carcinoma Cells ◽

Induced Apoptosis ◽

The Impact

Aims: Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. Methods: In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied. The changed proteins were identified by Western blot and siRNA methods. Results: Two-dimensional electrophoresis revealed changes that occurred to the cells when treated with or without GA. Four up-regulated protein spots were clearly identified as malate dehydrogenase (MDH), voltagedependent, anion-selective channel protein 1(VDAC1), calreticulin (CRT) and brain acid soluble protein 1(BASP1). VDAC1 in A549 cells was reconfirmed by western blot. Transfection with VDAC1 siRNA significantly increased cell viability after the treatment of GA. Further investigation showed that GA down regulated PI3K/Akt signaling pathways. These data strongly suggest that up-regulation of VDAC1 by GA may play an important role in GA-induced, inhibitory effects on A549 cell viability.

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Simple Thalidomide Analogs in Melanoma: Synthesis and Biological Activity

Applied Sciences ◽

10.3390/app11135823 ◽

2021 ◽

Vol 11 (13) ◽

pp. 5823

Author(s):

Alexia Barbarossa ◽

Alessia Catalano ◽

Jessica Ceramella ◽

Alessia Carocci ◽

Domenico Iacopetta ◽

...

Keyword(s):

Anticancer Agent ◽

Ring System ◽

In Vitro Assays ◽

Tubulin Polymerization ◽

Cytotoxic Effects ◽

Ongoing Research ◽

Drug Candidates ◽

Small Series ◽

Clinical Interest

Thalidomide is an old well-known drug that is still of clinical interest, despite its teratogenic activities, due to its antiangiogenic and immunomodulatory properties. Therefore, efforts to design safer and effective thalidomide analogs are continually ongoing. Research studies on thalidomide analogs have revealed that the phthalimide ring system is an essential pharmacophoric fragment; thus, many phthalimidic compounds have been synthesized and evaluated as anticancer drug candidates. In this study, a panel of selected in vitro assays, performed on a small series of phthalimide derivatives, allowed us to characterize compound 2k as a good anticancer agent, acting on A2058 melanoma cell line, which causes cell death by apoptosis due to its capability to inhibit tubulin polymerization. The obtained data were confirmed by in silico assays. No cytotoxic effects on normal cells have been detected for this compound that proves to be a valid candidate for further investigations to achieve new insights on possible mechanism of action of this class of compounds as anticancer drugs.

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