Arginine modification of lycosin-I to improve inhibitory activity against cancer cells

2017 ◽  
Vol 15 (44) ◽  
pp. 9379-9388 ◽  
Author(s):  
Peng Zhang ◽  
Jing Ma ◽  
Yujie Yan ◽  
Bo Chen ◽  
Bobo Liu ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Solid Tumor ◽  
Inhibitory Activity ◽  
High Serum ◽  
Serum Stability ◽  
Arginine Modification

Herein, arginine modification rendered Lycosin-I with higher anticancer activity, penetrability, and dissemination ability against solid tumor cells due to the optimized physicochemical properties and high serum stability.

Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths

2019 ◽  
Vol 15 (5) ◽  
pp. 550-560
Author(s):  
Mateusz D. Tomczyk ◽  
Anna Byczek-Wyrostek ◽  
Klaudia Strama ◽  
Martyna Wawszków ◽  
Przemysław Kasprzycki ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Topoisomerase Ii ◽  
Significant Activity ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
Substitution Pattern ◽  
Topo Ii

Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Methods: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

Hsp90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin

2004 ◽  
Vol 113 (2) ◽  
pp. 179-188 ◽  
Author(s):  
Rochelle Bagatell ◽  
Jason Beliakoff ◽  
Cynthia L. David ◽  
Marilyn T. Marron ◽  
Luke Whitesell
Keyword(s):  
Anticancer Activity ◽  
Tumor Cells ◽  
Solid Tumor ◽  
Hsp90 Inhibitors ◽  
Pediatric Solid Tumor ◽  
Apoptotic Proteins

scholarly journals Dimers of Melampomagnolide B Exhibit Potent Anticancer Activity against Hematological and Solid Tumor Cells

2015 ◽  
Vol 58 (22) ◽  
pp. 8896-8906 ◽  
Author(s):  
Venumadhav Janganati ◽  
Jessica Ponder ◽  
Craig T. Jordan ◽  
Michael J. Borrelli ◽  
Narsimha Reddy Penthala ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Tumor Cells ◽  
Solid Tumor

scholarly journals Validity of current experimental evidence on laparoscopic surgery for colorectal cancer

2004 ◽  
Vol 51 (2) ◽  
pp. 43-44
Author(s):  
R. Bergamaschi
Keyword(s):  
Colorectal Cancer ◽  
Laparoscopic Surgery ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Solid Tumor ◽  
Intraperitoneal Injection ◽  
Human Population ◽  
Animal Studies ◽  
Sigmoid Resection ◽  
Controversial Area

Experimental animal studies can provide crucial evidence for the evaluation and refinement of the controversial area of many areas of surgery. Recently, during the surge in interest in laparoscopic surgery, in particular for colorectal cancer, 72 animal studies have been published between 1995 and 2001. However, the question remains as to which of theses data can be suitably extrapolated to the human population. Forty-five of 47 studies, which use cell suspensions, relied on percutaneous intraperitoneal injection of cancer cells to induce peritoneal carcinomatosis. One study described a laparotomybased model with injection of tumor cells into the cecal lumen while a different study3 presented the cancer cells via enema. In this study, sigmoid resection was performed before colorectal solid tumor growth.

scholarly journals CYTOTOXIC ACTIVITY AND PHYSICOCHEMICAL PROPERTIES OF GENDARUSIN A-E COMPOUNDS ON ESTROGEN ALFA RECEPTORS (2JF9)

2020 ◽  
Vol 4 (1) ◽  
pp. 56
Author(s):  
Yen Yen Ari Indrawijaya ◽  
Nur Ika Octavia ◽  
Roihatul Mutiah ◽  
Weka Sidha Bhagawan ◽  
Burhan Ma'arif
Keyword(s):  
Molecular Docking ◽  
Physicochemical Properties ◽  
Cytotoxic Activity ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Receptor Protein ◽  
Toxicity Prediction ◽  
Online Tool ◽  
Molegro Virtual Docker

<em>Estrogen Alfa (ERα) is a receptor used as the main marker to identify the presence of tumors in the breast.compounds Gendarusin A-E have anticancer activity by inhibiting the poliferation of cancer cells and inducing apoptosis. The purpose of this research are to predict the cytotoxic activity, physicochemical properties, and toxicity of the gendarusin A-E compound. The predictions of physicochemical properties were tested in compliance with the Five Lipinski Rules and the results of the ADME process (absorption, distribution, metabolism, and excretion) using the application pkCSM Online tool. Prediction of cytotoxic activity using Molegro Virtual Docker (MVD) by validating receptors and molecular docking. Cancer receptor protein used in Estrogen Alfa with PDB code 2JF9. Toxicity prediction using the Protox II Online tool. The results of this study indicate that the Gendarusin A-E compound didn’t completed the Five Lipinski Rules. Gendarusin A-E compounds had activity against receptors Estrogen Alpha which is shown by the results of RMSD &lt;2 and Gendarusin A compounds had the smallest Rerank Score of -70.9817 compared to other compounds. Gendarusin B compound had the highest LD50  1212 mg / kg and classified in grade 4.</em>

scholarly journals DT2216, a Synthetic Proteolytic Selectively Targeting Bcl-XL for Ubiquitination and Degradation in Tumor Cells but Not in Platelets, Is a Safer and More Potent Antitumor Agent Than Navitoclax

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2698-2698
Author(s):  
Sajid Khan ◽  
Xuan Zhang ◽  
Dongwen Lv ◽  
Yonghan He ◽  
Peiyi Zhang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Solid Tumor ◽  
Patent Application ◽  
Single Agent ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Anti Cancer

Abstract The evasion of apoptosis, or programmed cell death, is a hallmark of cancer, which promotes tumor initiation and progression. The evasion is in part attributable to the over-expression of anti-apoptotic proteins in the Bcl-2 family. In addition, chemotherapy and radiation can upregulate the expression of the Bcl-2 family in cancer cells, which renders them more resistance to cancer therapy. The most common Bcl-2 family member over-expressed in many solid tumor cells and a fraction of leukemia and lymphoma cells is Bcl-XL and its expression is also highly correlated with resistance to cancer therapy independent of p53 status in many cancers. Therefore, Bcl-XL is one of the most important validated cancer cell targets. Inhibition of Bcl-XL with a small molecule inhibitor has been extensively exploited as a molecularly targeted therapeutic strategy against cancer, resulting in the discovery of several Bcl-2/XL and Bcl-XL inhibitors as promising anti-cancer drug candidates including navitoclax. Unfortunately, these inhibitors failed to become anticancer drugs because platelets are also dependent on Bcl-XL for survival. Therefore, inhibition of Bcl-XL with Bcl-2/XL and Bcl-XL inhibitors causes severe reduction in platelets or thrombocytopenia, an on-target and dose-limiting toxicity, which prevents their use as an effective anticancer drug in clinic. To overcome this problem, we generated a series of novel bifunctional molecules that targeting Bcl-XL to the ubiquitin-proteasome system (UPS) for degradation. These synthetic proteolytic compounds, termed synthetic proteolytics (Syntholytics) or proteolysis targeting chimeras (PROTACs), were rationally designed to recruit the Von Hippel Lindau (VHL) E3 ligase to ubiquitinate Bcl-XL for degradation by the proteasome. Because VHL is minimally expressed in platelets, our Bcl-XL Syntholytics can selectively induce Bcl-XL degradation in various cancer cells but not in platelets. Amongst these Bcl-XL Syntholytics, DT2216 was found to be the most potent in inducing Bcl-XL degradation leading to the loss of viability of Bcl-XL-dependent T-ALL MOLT-4 cells at nanomolar concentrations but did not cause any platelet toxicity. Compared to navitoclax, DT2216 is more potent in induction of apoptosis in a variety of cancer and leukemia cells in vitro in a caspase-dependent manner. Furthermore, our in vivo studies in immunocompromised mice revealed that DT2216 at 15 mg/kg/wk potently inhibited tumor growth in Bcl-XL-dependent MOLT-4 T-ALL xenografts as a single agent whereas navitoclax had no significant effect at the same dosage. Dosing with DT2216 at 15 mg/kg every four days significantly regressed larger established MOLT-4 T-ALL tumors that failed to respond to navitoclax treatment. To assess the therapeutic potential of DT2216 in combination with other Bcl-2 family inhibitors, we employed the Bcl-2/xl dependent NCI-H146 small cell lung cancer cells and the Mcl1/Bcl-xl dependent multiple myeloma EJM cells. The combination of DT2216 with Bcl-2 inhibitor (ABT199) or Mcl-1 inhibitor (S63845) synergistically reduced the viability of H146 and EJM cells, respectively. DT2216 in combination with ABT199 effectively inhibited tumor growth in H146 xenografts. Collectively, our findings suggest that targeting Bcl-XL using Bcl-XL Syntholytics can selectively kill Bcl-XL-dependent T-ALL cells and various solid tumor cells without causing significant platelet toxicity. Moreover, the combination of Bcl-XL Syntholytics with other Bcl-2 protein inhibitors could be used to effectively target multiple cancer types including both hematological and solid tumors. Therefore, Bcl-XL Syntholytics have the potential to be developed as safer and more potent novel anti-cancer drugs. Keywords: Bcl-XL, VHL, Protein degradation, T-ALL, Cancer, Apoptosis Disclosures: S.K., X.Z., D.L., Y.H., P.Z., X. L., G. Z., and D.Z. are inventors of a pending patent application for use of Bcl-xl syntholytics as anti-cancer agents. R.H, G.Z. and D.Z. are co-founders of Dialectic Therapeutics that develops Bcl-xl syntholytics. Disclosures Khan: Dialectic Therapeutics: Patents & Royalties. Lv:Dialectic Therapeutics: Patents & Royalties. He:Dialectic Therapeutics: Patents & Royalties. Zhang:Dialectic Therapeutics: Patents & Royalties. Liu:Dialectic Therapeutics: Patents & Royalties. Konopleva:Stemline Therapeutics: Research Funding. Zheng:Dialectic Therapeutics: Consultancy, Equity Ownership, Patents & Royalties.

Role of exosomes in diagnosis and therapy of prostate cancer

2020 ◽  
Vol 28 (3) ◽  
pp. 399-405
Author(s):  
Fabrizio Fontana ◽  
Olga A. Babenko
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Biological Fluids ◽  
Diagnosis And Treatment ◽  
Diagnosis And Therapy ◽  
The Future ◽  
Important Direction ◽  
Potential Biomarkers

Aim of this letter is to attract the attention of journal readers to the study of exosomes as an important direction in the development of Oncology, in particular, in the diagnosis and treatment of prostate cancer. Exosomes are produced by tumor cells and regulate proliferation, metastasis, and the development of chemoresistance. Their extraction from biological fluids allows further use of these vesicles as potential biomarkers of prostate cancer. In the future, exosomes can be successfully used in the delivery of drugs and other anti-tumor substances to cancer cells.

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