Tetrahydrocurcumin, Curcumin, and 5-Fluorouracil Effects on Human Esophageal Carcinoma Cells

Background: Esophageal cancer responds poorly to traditional therapies, and novel treatments are needed. The phytochemical curcumin is a potential treatment for Esophageal Squamous Cell Carcinoma (ESCC). A curcumin metabolite, tetrahydrocurcumin (THCUR), has anti-cancer effects and greater bioavailability than curcumin. Objective: Evaluate THCUR as an anti-cancer agent relative to curcumin and a standard cancer drug, 5-fluorouracil (5-FU), along with treatment interactions. Materials and Methods: Assay cell proliferation and viability following individual and combined delivery of the compounds to three ESSC cell lines (TE-1, TE-8, and KY-5) that have different percentages of Cancer Stem Cells (CSCs). Results: Curcumin was significantly more effective than 5-FU in all three cell lines. It also had the greatest effect on KY-5 cells, which have the highest CSC properties, consistent with the ability of curcumin to target CSCs. Effects on ESCC cell proliferation were not detected from 40µM THCUR, a dosage above the IC50 of curcumin and 5-FU. However, THCUR at this dosage in combination with 5-FU significantly suppressed TE-1 cell proliferation, but 5-FU alone did not. As TE-1 has low CSC properties relative to the two other cell lines, it was expected to have the least resistance to chemotherapeutic treatments. Surprisingly, TE-1 was the most resistant to inhibition by 5-FU. Conclusion: These results and the greater stability and water solubility of THCUR than curcumin support further testing of THCUR in combination with standard treatments, particularly for chemoresistant ESCC. In contrast to concerns that curcuminoids taken by patients through diet or diet supplements might interfere with chemotherapy, suppression of 5-FU efficacy by curcumin was not observed.

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Furanoic Lipid F-6, A Novel Anti-Cancer Compound that Kills Cancer Cells by Suppressing Proliferation and Inducing Apoptosis

Cancers ◽

10.3390/cancers11070960 ◽

2019 ◽

Vol 11 (7) ◽

pp. 960 ◽

Cited By ~ 2

Author(s):

Jassim M. Al-Hassan ◽

Yuan Fang Liu ◽

Meraj A. Khan ◽

Peiying Yang ◽

Rui Guan ◽

...

Keyword(s):

Cell Proliferation ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Neutrophil Extracellular Trap ◽

Cancer Drug ◽

Drug Candidate ◽

Cell Recovery ◽

Network Analyses ◽

Anti Cancer

Identifying novel anti-cancer drugs is important for devising better cancer treatment options. In a series of studies designed to identify novel therapeutic compounds, we recently showed that a C-20 fatty acid (12,15-epoxy-13,14-dimethyleicosa-12,14-dienoic acid, a furanoic acid or F-6) present in the lipid fraction of the secretions of the Arabian Gulf catfish skin (Arius bilineatus Val.; AGCS) robustly induces neutrophil extracellular trap formation. Here, we demonstrate that a lipid mix (Ft-3) extracted from AGCS and F-6, a component of Ft-3, dose dependently kill two cancer cell lines (leukemic K-562 and breast MDA MB-231). Pure F-6 is approximately 3.5 to 16 times more effective than Ft-3 in killing these cancer cells, respectively. Multiplex assays and network analyses show that F-6 promotes the activation of MAPKs such as Erk, JNK, and p38, and specifically suppresses JNK-mediated c-Jun activation necessary for AP-1-mediated cell survival pathways. In both cell lines, F-6 suppresses PI3K-Akt-mTOR pathway specific proteins, indicating that cell proliferation and Akt-mediated protection of mitochondrial stability are compromised by this treatment. Western blot analyses of cleaved caspase 3 (cCasp3) and poly ADP ribose polymerase (PARP) confirmed that F-6 dose-dependently induced apoptosis in both of these cell lines. In 14-day cell recovery experiments, cells treated with increasing doses of F-6 and Ft-3 fail to recover after subsequent drug washout. In summary, this study demonstrates that C-20 furanoic acid F-6, suppresses cancer cell proliferation and promotes apoptotic cell death in leukemic and breast cancer cells, and prevents cell recovery. Therefore, F-6 is a potential anti-cancer drug candidate.

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SKA3 Promotes Cell Growth in Breast Cancer by Inhibiting PLK-1 Protein Degradation

Technology in Cancer Research & Treatment ◽

10.1177/1533033820947488 ◽

2020 ◽

Vol 19 ◽

pp. 153303382094748

Author(s):

Li-wei Ruan ◽

Peng-peng Li ◽

Lang-ping Jin

Keyword(s):

Breast Cancer ◽

Cervical Cancer ◽

Cell Proliferation ◽

Cell Growth ◽

Cell Lines ◽

Cancer Progression ◽

Cancer Drug ◽

Anti Cancer ◽

Mental And Physical Health

Breast cancer (Bca) remains the most common form of malignancy affecting females in China, leading to significant reductions in the mental and physical health of those with this condition. While spindle and kinetochore associated complex subunit 3 (SKA3) is known to be linked with cervical cancer progression, whether it is similarly associated with Bca progression remains unknown. Using shRNA, we specifically knocked down the expression of SKA3 in Bca cell lines and then assessed the resultant changes in cell proliferation using CCK-8 and colony formation assays. In addition, we used western blotting to quantify the expression levels of relevant proteins in these cells, and we assessed the interaction between SKA3 and polo-like kinase-1 (PLK-1) via co-immunoprecipitation.In this study, we observed elevated SKA3 expression in Bca tissues and cell lines. When we knocked down SKA3 expression in Bca cells, we were able to determine that it functions in an oncogenic manner so as to promote the growth and proliferation of these cells in vitro. From a mechanistic perspective, we were able to show that in Bca cells SKA functions at least in part via interacting with PLK-1 and preventing its degradation. In summary, we found that SKA3 is able to regulate PLK-1 degradation in Bca cells, thus controlling their growth and proliferation. These results highlight SKA3 as a potentially viable target for anti-cancer drug development aimed at combatting Bca.

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Triarylpyrazole Derivatives as Potent Cytotoxic Agents; Synthesis and Bioactivity Evaluation “Pyrazole Derivatives as Anticancer Agent”

Drug Research ◽

10.1055/a-1498-1714 ◽

2021 ◽

Author(s):

Bilqees Sameem ◽

Ebrahim Saeedian Moghadam ◽

Majid Darabi ◽

Zahra Shahsavari ◽

Mohsen Amini

Keyword(s):

Cell Lines ◽

Anticancer Agents ◽

Human Cancer ◽

Carcinoma Cells ◽

Cytotoxic Agents ◽

Cancer Drug ◽

Pyrazole Derivatives ◽

Anti Cancer ◽

Ht 29

Abstract Background During the last recent years, several anti-cancer agents were introduced for the treatment of diverse kinds of cancer. Despite their potential in the treatment of cancer, drug resistance and adverse toxicity such as peripheral neuropathy are some of the negative criteria of anti-cancer agents and for this reason, the design and synthesis of new anti-cancer agents are important. Objective Design, synthesis, and anticancer activity evaluation of some pyrazole derivatives. Methods A series of Target compounds were prepared using multistep synthesis. Their cytotoxic activity against three different human cancer cell lines namely human colon carcinoma cells (HT-29), epithelial carcinoma cells (U-87MG), pancreatic cancerous cells (Panc-1) as well as AGO1522 normal cell line using in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was investigated. Results 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)- 1H-pyrazole were synthesized in good yields and their structure and purity were confirmed using 1H-NMR, 13C-NMR, and elemental analysis. Generally, the synthesized scaffolds exhibited good cytotoxicity against cancerous cell lines in comparison to the reference standard, paclitaxel. Compounds 3a and 3c, in Annexin V/ PI staining assay, exerted remarkable activity in apoptosis induction in HT-29 cell lines. Both of them also led to cell cycle arrest in the sub-G1 phase which is inconsistent with the results of apoptosis assay. Conclusion Concerning obtained results, it is interesting to synthesis more pyrazole derivatives as anticancer agents.

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Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200409142239 ◽

2020 ◽

Vol 20 (8) ◽

pp. 1017-1027

Author(s):

Abdul M. Baig ◽

Zohaib Rana ◽

Mohammad M. Mannan ◽

Areeba Khaleeq ◽

Fizza Nazim ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Drug Efflux ◽

Adapter Proteins ◽

Cancer Drugs ◽

Protein Targets ◽

Anti Cancer ◽

Drug Efflux Pumps ◽

Cancer Agent ◽

Androgen Independent

Background: Targeting evolutionarily conserved proteins in malignant cells and the adapter proteins involved in signalling that generates from such proteins may play a cardinal role in the selection of anti-cancer drugs. Drugs targeting these proteins could be of importance in developing anti-cancer drugs. Objectives: We inferred that drugs like loperamide and promethazine that act as antagonists of proteins conserved in cancer cells like voltage-gated Calcium channels (Cav), Calmodulin (CaM) and drug efflux (ABCB1) pump may have the potential to be re-purposed as an anti-cancer agent in Prostate Cancer (PCa). Methods: Growth and cytotoxic assays were performed by selecting loperamide and promethazine to target Cav, CaM and drug efflux (ABCB1) pumps to elucidate their effects on androgen-independent PC3 and DU145 PCa cell lines. Results: We show that loperamide and promethazine in doses of 80-100μg/ml exert oncocidal effects when tested in DU145 and PC3 cell lines. Diphenhydramine, which shares its targets with promethazine, except the CaM, failed to exhibit oncocidal effects. Conclusion: Anti-cancer effects can be of significance if structural analogues of loperamide and promethazine that specifically target Cav, CaM and ABCB1 drug efflux pumps can be synthesized, or these two drugs could be re-purposed after human trials in PCa.

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Sulforaphane suppresses autophagy during the malignant progression of gastric carcinoma via activating miR-4521/PIK3R3 pathway

Human & Experimental Toxicology ◽

10.1177/09603271211054437 ◽

2021 ◽

pp. 096032712110544

Author(s):

Zi-tan Peng ◽

Pei Gu

Keyword(s):

Cell Proliferation ◽

Gastric Carcinoma ◽

Carcinoma Cells ◽

Malignant Progression ◽

Gastric Carcinoma Cell ◽

Over Expression ◽

Anti Cancer ◽

Underlying Mechanisms ◽

Cruciferous Plants

Objective Sulforaphane, which exerts an effective anti-cancer ability, is a phytochemical converted from cruciferous plants. Here, we aimed to identify whether sulforaphane could suppress autophagy during the malignant progression of gastric carcinoma and to explore the underlying mechanisms. Methods SGC7901 cells were transfected with miR-4521 mimics, inhibitor, and pcDNA3.1- PIK3R3, and treated with sulforaphane or autophagy inhibitor. Cell proliferation, apoptosis, and miR-4521 or PIK3R3 expression were detected. Results MiR-4521 over-expression suppressed LC3-II/I ratio and Beclin-1 expression but induced p62 expression in SGC7901 cells. MiR-4521 also reduced gastric carcinoma cell proliferation and promoted apoptosis in vitro. In the mechanical observation, we identified that miR-4521 directly targeted PIK3R3 to repress its expression, and PIK3R3 up-regulation partly antagonized miR-4521-mediated autophagy, proliferation, and apoptosis in gastric carcinoma cells. In addition, sulforaphane exerted effective anti-cancer functions by repressing autophagy and growth in tumor cells at a concentration-dependent way. MiR-4521 inhibition or PIK3R3 over-expression weakened the anti-cancer functions of sulforaphane in gastric carcinoma cells. Conclusion Consequently, miR-4521 suppressed autophagy during the malignant progression of gastric carcinoma by targeting PIK3R3. Thus, miR-4521 may be applied as a therapeutic target for sulforaphane in gastric carcinoma.

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Immobilization of l-asparaginase on gold nanoparticles for novel drug delivery approach as anti-cancer agent against human breast carcinoma cells

Journal of Materials Research and Technology ◽

10.1016/j.jmrt.2020.10.021 ◽

2020 ◽

Vol 9 (6) ◽

pp. 15394-15411

Author(s):

Ali G. Al-Dulimi ◽

Ali Z. Al-Saffar ◽

Ghassan M. Sulaiman ◽

Khalil A.A. Khalil ◽

Khawla S. Khashan ◽

...

Keyword(s):

Drug Delivery ◽

Gold Nanoparticles ◽

Carcinoma Cells ◽

Human Breast ◽

Breast Carcinoma Cells ◽

Anti Cancer ◽

Human Breast Carcinoma Cells ◽

Cancer Agent ◽

Novel Drug ◽

Delivery Approach

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The Design and Synthesis of Novel Phenothiazine Derivatives as Potential Cytotoxic Agents

Letters in Drug Design & Discovery ◽

10.2174/1570180816666181115112236 ◽

2019 ◽

Vol 17 (1) ◽

pp. 57-67

Author(s):

Yepeng Luan ◽

Jinyi Liu ◽

Jianjun Gao ◽

Jinhua Wang

Keyword(s):

Cell Lines ◽

High Efficiency ◽

Human Cancer ◽

Human Tumor ◽

Cytotoxic Agents ◽

Cancer Drug ◽

Human Cancer Cell Lines ◽

Incidence And Mortality ◽

Anti Cancer

Background: Cancer incidence and mortality have been increasing and cancer is still the leading cause of death all over the world. Despite the enormous progress in cancer treatment, many patients died of ineffective chemotherapy and drug resistance. Therefore, the design and development of anti-cancer drugs with high efficiency and low toxicity is still one of the most challenging tasks. Tricyclic heterocycles, such as phenothiazine, are always important sources of scaffolds for anti-cancer drug discovery. Methods: In this work, ten new urea-containing derivatives of phenothiazine coupled with different kinds of amine motifs at the endpoint through a three carbon long spacer were designed and synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR and HRMS. All the synthesized compounds were tested for their antitumor activity in vitro against the proliferation of PC-3 cells, and the compounds with best potency entered further cytotoxicity evaluations against other 22 human tumor cell lines. Mechanism was also studied. Results: From all data, it showed that among all 10 target compounds, TTi-2 showed the best effect in inhibiting the proliferation of 23 human cancer cell lines while TTi-2 without obvious inhibitory effect on normal cell. Furthermore, our results also showed that TTi-2 could inhibit migration, invasion and colony formation of MDA-MB-231 cells. Finally, TTi-2 can induce arrest of cell cycle at G0/G1 phase and cell apoptosis by activating the caspase 3 activity. Conclusion: All these results suggested that TTi-2 might be used as a promising lead compound for anticancer drug development.

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3′,4′-Dihydro-2′H-spiro[indoline-3,1′-isoquinolin]-2-ones as potential anti-cancer agents: synthesis and preliminary screening

Royal Society Open Science ◽

10.1098/rsos.191316 ◽

2020 ◽

Vol 7 (1) ◽

pp. 191316 ◽

Cited By ~ 1

Author(s):

Maloba M. M. Lobe ◽

Simon M. N. Efange

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Biological Activities ◽

Cell Cancer ◽

Breast Cancer Cell Lines ◽

Small Cell Lung ◽

Preliminary Screening ◽

Anti Cancer ◽

Molecular Hybrids

Both tetrahydroisoquinolines (THIQs) and oxindoles (OXs) display a broad range of biological activities including anti-cancer activity, and are therefore recognized as two privileged scaffolds in drug discovery. In the present study, 24 3′,4′-dihydro-2′H-spiro[indoline-3,1′-isoquinolin]-2-ones, designed as molecular hybrids of THIQ and OX, were synthesized and screened in vitro against 59 cell lines in the NCI-60 screen. Twenty compounds displayed weak to moderate inhibition of cell proliferation; among them, three compounds displayed at least 50% inhibition of cell proliferation. The compounds appeared to target primarily renal cell cancer lines; however, leukaemia, melanoma, non-small cell lung cancer, prostate, ovarian and even breast cancer cell lines were also affected. Therefore, this class of spirooxindoles may provide useful leads in the search for new anti-cancer agents.

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Development of a Cationic Amphiphilic Helical Peptidomimetic (B18L) As A Novel Anti-Cancer Drug Lead

Cancers ◽

10.3390/cancers12092448 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2448 ◽

Cited By ~ 1

Author(s):

Yuan Lyu ◽

Steven Kopcho ◽

Folnetti A. Alvarez ◽

Bryson C. Okeoma ◽

Chioma M. Okeoma

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Cancer Drug ◽

Cancer Cell Death ◽

Drug Lead ◽

Anti Cancer ◽

Cancer Agent ◽

Caspase Substrate ◽

Dynamics Simulations

BST-2 is a novel driver of cancer progression whose expression confers oncogenic properties to breast cancer cells. As such, targeting BST-2 in tumors may be an effective therapeutic approach against breast cancer. Here, we sought to develop potent cytotoxic anti-cancer agent using the second-generation BST-2-based anti-adhesion peptide, B18, as backbone. To this end, we designed a series of five B18-derived peptidomimetics. Among these, B18L, a cationic amphiphilic α-helical peptidomimetic, was selected as the drug lead because it displayed superior anti-cancer activity against both drug-resistant and drug-sensitive cancer cells, with minimal toxicity on normal cells. Probing mechanism of action using molecular dynamics simulations, biochemical and membrane biophysics studies, we observed that B18L binds BST-2 and possesses membranolytic characteristics. Furthermore, molecular biology studies show that B18L dysregulates cancer signaling pathways resulting in decreased Src and Erk1/2 phosphorylation, increased expression of pro-apoptotic Bcl2 proteins, caspase 3 cleavage products, as well as processing of the caspase substrate, poly (ADP-ribose) polymerase-1 (PARP-1), to the characteristic apoptotic fragment. These data indicate that through the coordinated regulation of membrane, mitochondrial and signaling events, B18L executes cancer cell death and thus has the potential to be developed into a potent and selective anti-cancer compound.

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