scholarly journals Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance

2011 ◽  
Vol 108 (46) ◽  
pp. 18708-18713 ◽  
Author(s):  
J.-P. Gillet ◽  
A. M. Calcagno ◽  
S. Varma ◽  
M. Marino ◽  
L. J. Green ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
Anti Cancer

scholarly journals Molecular Simulations Identify Target Receptor Kinases Bound by Astaxanthin to Induce Breast Cancer Cell Apoptosis

2020 ◽  
pp. 72-82
Author(s):  
Mossa Gardaneh ◽  
Zahra Nayeri ◽  
Parvin Akbari ◽  
Mahsa Gardaneh ◽  
Hasan Tahermansouri
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Combination Therapy ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Breast Cancer Cell Lines

Background: We investigated molecular mechanisms behind astaxanthinmediated induction of apoptosis in breast cancer cell lines toward combination therapy against cancer drug resistance. Methods: Breast cancer cell lines were treated with serial concentrations of astaxanthin to determine its IC50. We used drug-design software to predict interactions between astaxanthin and receptor tyrosine kinases or other key gene products involved in intracellular signaling pathways. Changes in gene expression were examined using RT-PCR. The effect of astaxanthin-nanocarbons combinations on cancer cells was also evaluated. Results: Astaxanthin induced cell death in all three breast cancer cell lines was examined so that its IC50 in two HER2-amplifying lines SKBR3 and BT-474 stood, respectively, at 36 and 37 ?M; however, this figure for MCF-7 was significantly lowered to 23 ?M (P<0.05). Astaxanthin-treated SKBR3 cells showed apoptotic death upon co-staining. Our in silico examinations showed that some growth-promoting molecules are strongly bound by astaxanthin via their specific amino acid residues with their binding energy standing below -6 KCa/Mol. Next, astaxanthin was combined with either graphene oxide or carboxylated multi-walled carbon nanotube, with the latter affecting SKBR cell survival more extensively than the former (P<0.05). Finally, astaxanthin coinduced tumor suppressors p53 and PTEN but downregulated the expression of growth-inducing genes in treated cells. Conclusion: These findings indicate astaxanthin carries' multitarget antitumorigenic capacities and introduce the compound as a suitable candidate for combination therapy regimens against cancer growth and drug resistance. Development of animal models to elucidate interactions between the compound and tumor microenvironment could be a major step forward towards the inclusion of astaxanthin in cancer therapy trials.

scholarly journals Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1749 ◽  
Author(s):  
Lu Jin ◽  
Meng-Ling Wang ◽  
Yao Lv ◽  
Xue-Yi Zeng ◽  
Chao Chen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Hydroxyl Groups ◽  
Drug Candidates ◽  
Design And Synthesis ◽  
Anti Cancer ◽  
Clinical Drugs

Flavonoids are well-characterized polyphenolic compounds with pharmacological and therapeutic activities. However, most flavonoids have not been developed into clinical drugs, due to poor bioavailability. Herein, we report a strategy to increase the drugability of flavonoids by constructing C(sp2)-O bonds and stereo- as well as regioselective alkenylation of hydroxyl groups of flavonoids with ethyl-2,3-butadienoate allenes. Twenty-three modified flavonoid derivatives were designed, synthesized, and evaluated for their anti-cancer activities. The results showed that compounds 4b, 4c, 4e, 5e, and 6b exhibited better in vitro inhibitory activity against several cancer cell lines than their precursors. Preliminary structure–activity relationship studies indicated that, in most of the cancer cell lines evaluated, the substitution on position 7 was essential for increasing cytotoxicity. The results of this study might facilitate the preparation or late-stage modification of complex flavonoids as anti-cancer drug candidates.

Design, Synthesis and Biological Evaluation of 4, 6-Coumarin Derivatives as Anti-Cancer and Apoptosis-Inducing Agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Guoyi Yan ◽  
Jiang Luo ◽  
Xuan Han ◽  
Wenjuan Zhang ◽  
Chunlan Pu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Coumarin Derivatives ◽  
In Silico Admet ◽  
Anti Cancer ◽  
Synthesis And Biological Evaluation

BACKGROUND: : Coumarin structures were widely employed in anti-cancer drug design. Herein we focused on the modifications of C4 and C6 positions on coumarin scaffold to get novel anti-cancer agents. OBJECTIVE: The objective of the current work was the synthesis and biological evaluation of a series of 4, 6-coumarin derivatives to get novel anticancer agents. METHODS: Thirty-seven coumarin derivatives were designed and synthesized, the antiproliferative activity of the compounds were evaluated against human cancer cell lines and non-cancerous cells by MTT assay. The bioactivities and underling mechanisms of active molecules were studied and the ADMET characters were predicted. RESULTS: Among the compounds, 4-phydroxy phenol-6-pinacol borane coumarin (25) exhibited a promising anti-cancer activity to cancer cell lines in dose-dependent manner and the toxicity to normal cells was low. The mechanism of action was observed through inducing G2/M phase arrest and apoptosis which was further confirmed via western blot. In silico ADMET prediction revealed that compound 25 is a drug-like small molecule with a favorable safety profile. CONCLUSION: The findings in this work may give vital information for further development of 6-pinacol borane coumarin derivatives as novel anti-cancer agents.

scholarly journals PVA coating of ferrite nanoparticles triggers pH-responsive release of 5-fluorouracil in cancer cells

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sanele Mngadi ◽  
Moganavelli Singh ◽  
Seipati Mokhosi
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Targeted Delivery ◽  
Colloidal Stability ◽  
Therapeutic Potential ◽  
Cancer Cell Lines ◽  
Ferrite Nanoparticles ◽  
Cancer Drug ◽  
Anti Cancer

Abstract The use of magnetic nanoparticles (MNPs) has transformed both diagnostics and therapeutic approaches in cancer treatment. Along with developing novel anti-cancer drugs with high therapeutic potential, researchers are exploring innovative strategies for more targeted delivery in order to alleviate the associated potent side effects. In this study, we describe the synthesis of Mg0.5Co0.5Fe2O4 ferrite nanoparticles, their functionalisation with polyvinyl alcohol (PVA), and encapsulation of the anti-cancer drug 5-fluorouracil (5-FU). Functionalised nanoparticles viz. PVA-Mg0.5Co0.5Fe2O4 -5-FU displayed desirable physiochemical properties with regards to the spherical shape, hydrodynamic sizes of <120 nm and relative colloidal stability of up to <−33 mV. The drug encapsulating efficiency was found to be 68%. In vitro cytotoxicity profiles were determined using the MTT and SRB assays, with >65% cell death recorded in MCF-7 and HeLa cancer cell lines. Overall, the nanocomposites exhibited excellent physiochemical elements, high specificity towards cancerous cells and displayed pH-sensitive drug release in a simulated acidic tumour micro-environment. The encapsulation of 5-FU improved bioavailability of the drug in cancer cell lines for a prolonged duration, with the promise to enhance its therapeutic effect, biocompatibility and safety. These MNPs present as promising in vitro delivery systems that can further developed for therapeutic applications.

Genome-Wide siRNA Screen for Anti-Cancer Drug Resistance in Adherent Cell Lines

BIO-PROTOCOL ◽  
2015 ◽  
Vol 5 (10) ◽  
Author(s):  
Elza de Bruin ◽  
Ming Jiang ◽  
Michael Howell ◽  
Julian Downward
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Drug ◽  
Adherent Cell ◽  
Sirna Screen ◽  
Cancer Drug Resistance ◽  
Genome Wide ◽  
Anti Cancer

Dual Anti-cancer and Anti-Itch Activity of PD176252 Analogues: Design, Synthesis and Biological Evaluation

2019 ◽  
Vol 19 (8) ◽  
pp. 992-1001 ◽  
Author(s):  
Ming-Jun Yu ◽  
Sen Yao ◽  
Ting-Ting Li ◽  
Rui Yang ◽  
Ri-Sheng Yao
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Normal Lung ◽  
Cancer Drug ◽  
Normal Cells ◽  
Anti Cancer ◽  
Grpr Antagonist ◽  
Cancer Activity

Background: Cancer patients treated with targeted anti-cancer drug suffer from itch or pruritus. Itch or pruritus is an unpleasant sensation that brings about a negative impact on quality of life, and serious itch may lead to dose reduction and even discontinuation. Gastrin releasing peptide receptor (GRPR) plays a critical role in itch, inflammation and cancer, and GRPR antagonist has obvious effect on cancer, inflammation and itch. The aim of this paper is to develop a new agent with anti-cancer and anti-itch activity. Methods: A series of GRPR antagonist PD176252 analogues (3a-3l) were designed and synthesized. Both anticancer and anti-itch activities were evaluated. Anti-cancer activity was evaluated in three human cancer cell lines in vitro, the anti-itch activity in evaluated with Kunming mice by intrathecal injection of chloroquine phosphate as a modeling medium. And the cytotoxicity on normal cells was evaluated. Results: Of the tested compounds, compound 3i showed potently anti-cancer activity to all cancer cell lines tested with IC50 values of 10.5µM (lung), 11.6µM (breast) and 12.8µM (liver) respectively and it also showed significant inhibition of the scratching behavior. Comparing with PD17625, compound 3i and 3g gave better inhibition activities against all cancer cell lines, compound 3b, 3c and 3i showed better anti-itch activity. The compound 3i is safe for normal breast and liver normal cells, but it has high cytotoxicity on normal lung cell. Conclusion: The synthesized compounds have dual anti-cancer and anti-itch activity, so the development of drug with dual anti-tumor and anti-itch property is possible.

scholarly journals Mathematical model of hypoxia and tumor signaling interplay reveals the importance of hypoxia and cell-to-cell variability in tumor growth inhibition

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Emile P. Chen ◽  
Roy S. Song ◽  
Xueer Chen
Keyword(s):  
Protein Kinase ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Tumor ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Cell To Cell Variability

Abstract Background Human tumor is a complex tissue with multiple heterogeneous hypoxic regions and significant cell-to-cell variability. Due to the complexity of the disease, the explanation of why anticancer therapies fail cannot be attributed to intrinsic or acquired drug resistance alone. Furthermore, there are inconsistent reports of hypoxia-induced kinase activities in different cancer cell-lines, where increase, decreases, or no change has been observed. Thus, we asked, why are there widely contrasting results in kinase activity under hypoxia in different cancer cell-lines and how does hypoxia play a role in anti-cancer drug sensitivity? Results We took a modeling approach to address these questions by analyzing the model simulation to explain why hypoxia driven signals can have dissimilar impact on tumor growth and alter the efficacy of anti-cancer drugs. Repeated simulations with varying concentrations of biomolecules followed by decision tree analysis reveal that the highly differential effects among heterogeneous subpopulation of tumor cells could be governed by varying concentrations of just a few key biomolecules. These biomolecules include activated serine/threonine-specific protein kinases (pRAF), mitogen-activated protein kinase kinase (pMEK), protein kinase B (pAkt), or phosphoinositide-4,5-bisphosphate 3-kinase (pPI3K). Additionally, the ratio of activated extracellular signal-regulated kinases (pERK) or pAkt to its respective total was a key factor in determining the sensitivity of pERK or pAkt to hypoxia. Conclusion This work offers a mechanistic insight into how hypoxia can affect the efficacy of anti-cancer drug that targets tumor signaling and provides a framework to identify the types of tumor cells that are either sensitive or resistant to anti-cancer therapy.

scholarly journals Prospective pharmacological methodology for establishing and evaluating anti-cancer drug resistant cell lines

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hoon Yu ◽  
Dong-Jin Kim ◽  
Hye-Young Choi ◽  
So Myoung Kim ◽  
Md. Intazur Rahaman ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Evaluation Methodology ◽  
Cross Resistance ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Resistance Evaluation ◽  
Cancer Drug Resistance ◽  
Anti Cancer

Abstract Background Cell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible. However, the process for establishing anti-cancer drug resistance in cell cultures in vitro and the subsequent method of then evaluating resistance are not clearly established. Traditionally, the IC50 is the most commonly used indicator of resistance evaluation but it cannot represent the effectiveness of anti-cancer drugs in a clinical setting and lacks reliability because it is heavily affected by the cell doubling time. Hence, new indicators that can evaluate anti-cancer drug resistance are needed. Methods A novel resistance evaluation methodology was validated in this present study by establishing sunitinib resistance in renal cell carcinoma cells and assessing the cross-resistance of five different anti-cancer drugs. Results It was confirmed in this present study that the IC50 does not reflect the cell proliferation rates in a way that represents anti-cancer drug resistance. An alternative indicator that can also be clinically meaningful when using in vitro cell line systems is GI100. Additionally, the GR100 allows different cell populations to be calibrated on the same basis when multiple experimental results are compared. Conclusion Since the GR100 has properties that indicate the efficiency of anti-cancer drugs, both the efficacy and GR100 of a particular anti-cancer drug can be used to effectively assess the resistance.

scholarly journals GDSCTools for Mining Pharmacogenomic Interactions in Cancer

2017 ◽  
Author(s):  
Thomas Cokelaer ◽  
Elisabeth Chen ◽  
Francesco Iorio ◽  
Michael P. Menden ◽  
Howard Lightfoot ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Data Structures ◽  
Human Cancer ◽  
Genomic Data ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Data Sets ◽  
Drug Responses ◽  
Anti Cancer

AbstractMotivationLarge pharmacogenomic screenings integrate heterogeneous cancer genomic data sets as well as anti-cancer drug responses on thousand human cancer cell lines. Mining this data to identify new therapies for cancer sub-populations would benefit from common data structures, modular computational biology tools and user-friendly interfaces.ResultsWe have developed GDSCTools: a software aimed at the identification of clinically relevant genomic markers of drug response. The Genomics of Drug Sensitivity in Cancer (GDSC) database (www.cancerRxgene.org) integrates heterogeneous cancer genomic data sets as well as anti-cancer drug responses on a thousand cancer cell lines. Including statistical tools (ANOVA) and predictive methods (Elastic Net), as well as common data structures, GDSCTools allows users to reproduce published results from GDSC, to analyse their own drug responses or genomic datasets, and to implement new analytical [email protected]

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