MiRNAs: A New Approach to Predict and Overcome Resistance to Anticancer Drugs

2020 ◽  
Vol 7 (2) ◽  
pp. 65-77
Author(s):  
Noor Altaleb
Keyword(s):  
Cancer Treatment ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cancer Chemotherapy ◽  
Mirna Expression ◽  
Chemotherapeutic Agents ◽  
Tumour Suppressor ◽  
New Approach ◽  
Cancer Data ◽  
Fundamental Units

Although there are no 100% successful methods for treating cancer, chemotherapy is still one of the most commonly used approaches in its management. One of the most significant problems in cancer treatment is the resistance of cancer cells to chemotherapeutic agents. This review aims to unveil the factors contributing to this problem originally beginning with fundamental units like biomarkers and microRNAs. As more studies and researches carried out, various levels of miRNA expression were found among normal and cancer cells. Overexpression of oncomir and downregulation of tumour-suppressor miRNAs can lead to the emergence of cancer. Data collected from studying these miRNAs can help in the diagnosis, prognosis and developing therapies, which will assist in overcoming the emerged resistance.

Pathogenesis and Treatment of Prostate Cancer Bone Metastases: Targeting the Lethal Phenotype

2005 ◽  
Vol 23 (32) ◽  
pp. 8232-8241 ◽  
Author(s):  
Robert D. Loberg ◽  
Christopher J. Logothetis ◽  
Evan T. Keller ◽  
Kenneth J. Pienta
Keyword(s):  
Prostate Cancer ◽  
Endothelial Cells ◽  
Tumor Cell ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Advanced Prostate Cancer ◽  
Metastatic Potential ◽  
Chemotherapeutic Agents ◽  
Bone Microenvironment ◽  
Lethal Phenotype

Traditionally, prostate cancer treatment, as well as all cancer treatment, has been designed to target the tumor cell directly via various hormonal and chemotherapeutic agents. Recently, the realization that cancer cells exist in complex microenvironments that are essential for the tumorigenic and metastatic potential of the cancer cells is starting the redefine the paradigm for cancer therapy. The propensity of prostate cancer cells to metastasize to bone is leading to the design of novel therapies targeting both the cancer cell as well as the bone microenvironment. Tumor cells in the bone interact with the extracellular matrix, stromal cells, osteoblasts, osteoclasts, and endothelial cells to promote tumor-cell survival and proliferation leading to a lethal phenotype that includes increased morbidity and mortality for patients with advanced prostate cancer. Several strategies are being developed that target these complex tumor cell–microenvironment interactions and target the signal transduction pathways of other cells important to the development of metastases, including the osteoclasts, osteoblasts, and endothelial cells of the bone microenvironment. Current and new therapies in metastatic prostate cancer will comprise a multitargeted approach aimed at both the tumor cell and the tumor microenvironment. Here, we review the current therapeutic strategies for targeting the prostate cancer–bone microenvironment and several single- and multiagent targeted approaches to the treatment of advanced prostate cancer that are under development.

scholarly journals Tetrandrine Interaction with ABCB1 Reverses Multidrug Resistance in Cancer Cells Through Competition with Anti-Cancer Drugs Followed by Downregulation of ABCB1 Expression

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4383 ◽  
Author(s):  
Dan Liao ◽  
Wei Zhang ◽  
Pranav Gupta ◽  
Zi-Ning Lei ◽  
Jing-Quan Wang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cellular Localization ◽  
Treatment Time ◽  
Mrna Level ◽  
Chemotherapeutic Agents ◽  
Mdr1 Gene ◽  
P Glycoprotein ◽  
Abcb1 Transporter

The overexpression of ABC transporters induced by anticancer drugs has been found to be the main cause of multidrug resistance. It is actually also a strategy by which cancer cells escape being killed. Tetrandrine is a natural product extracted from the stem of Tinospora crispa. In this study, tetrandrine showed synergistic cytotoxic activity in combinational use with chemotherapeutic drugs, such as Doxorubicin, Vincristine, and Paclitaxel, in both drug-induced and MDR1 gene-transfected cancer cells that over-expressed ABCB1/P-glycoprotein. Tetrandrine stimulated P-glycoprotein ATPase activity, decreased the efflux of [3H]-Paclitaxel and increased the intracellular accumulation of [3H]-Paclitaxel in KB-C2 cells. Furthermore, SW620/Ad300 and KB-C2 cells pretreated with 1 μM tetrandrine for 72 h decreased P-glycoprotein expression without changing its cellular localization. This was demonstrated through Western blotting and immunofluorescence analysis. Interestingly, down-regulation of P-glycoprotein expression was not correlated with gene transcription, as the MDR1 mRNA level exhibited a slight fluctuation in SW620/Ad300 and KB-C2 cells at 0, 24, 48, and 72 h treatment time points. In addition, molecular docking analysis predicted that tetrandrine had inhibitory potential with the ABCB1 transporter. Our results suggested that tetrandrine can antagonize MDR in both drug-selected and MDR1 gene-transfected cancer cells by down regulating the expression of the ABCB1 transporter, followed by increasing the intracellular concentration of chemotherapeutic agents. The combinational therapy using tetrandrine and other anticancer drugs could promote the treatment efficiency of drugs that are substrates of ABCB1.

A Review on Targeting Nanoparticles for Breast Cancer

2019 ◽  
Vol 20 (13) ◽  
pp. 1087-1107 ◽  
Author(s):  
Hasanain Gomhor J. Alqaraghuli ◽  
Soheila Kashanian ◽  
Ronak Rafipour
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Targeted Drug Delivery ◽  
Breast Cancer Cells ◽  
Pharmaceutical Research ◽  
Chemotherapeutic Agents ◽  
Great Promise ◽  
Targeted Drug

Chemotherapeutic agents have been used extensively in breast cancer remedy. However, most anticancer drugs cannot differentiate between cancer cells and normal cells, leading to toxic side effects. Also, the resulted drug resistance during chemotherapy reduces treatment efficacy. The development of targeted drug delivery offers great promise in breast cancer treatment both in clinical applications and in pharmaceutical research. Conjugation of nanocarriers with targeting ligands is an effective therapeutic strategy to treat cancer diseases. In this review, we focus on active targeting methods for breast cancer cells through the use of chemical ligands such as antibodies, peptides, aptamers, vitamins, hormones, and carbohydrates. Also, this review covers all information related to these targeting ligands, such as their subtypes, advantages, disadvantages, chemical modification methods with nanoparticles and recent published studies (from 2015 to present). We have discussed 28 different targeting methods utilized for targeted drug delivery to breast cancer cells with different nanocarriers delivering anticancer drugs to the tumors. These different targeting methods give researchers in the field of drug delivery all the information and techniques they need to develop modern drug delivery systems.

scholarly journals Imidazole-modified deferasirox encapsulated polymeric micelles as pH-responsive iron-chelating nanocarrier for cancer chemotherapy

RSC Advances ◽  
2017 ◽  
Vol 7 (18) ◽  
pp. 11158-11169 ◽  
Author(s):  
Man Theerasilp ◽  
Punlop Chalermpanapun ◽  
Kanyawan Ponlamuangdee ◽  
Dusita Sukvanitvichai ◽  
Norased Nasongkla
Keyword(s):  
Iron Deficiency ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Chemotherapy ◽  
Polymeric Micelles ◽  
Iron Level ◽  
Release Behavior ◽  
Ph Responsive ◽  
Cellular Iron ◽  
Novel Strategy

Modified deferasirox encapsulated polymeric micelles demonstrate pH-responsive and ON–OFF release behavior to deplete the iron level in cancer cells. The cellular iron deficiency is a novel strategy for cancer treatment.

scholarly journals The role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Demet Cansaran-Duman ◽  
Sevcan Yangın ◽  
Betül Çolak
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Real Time ◽  
Microarray Analysis ◽  
Mirna Expression ◽  
Breast Cancer Cells ◽  
Mcf 7

Abstract Background Breast cancer is the most frequently diagnosed cancer, and no effective treatment solution has yet been found. The number of studies based on the research of novel natural compounds in the treatment of breast cancer has been increasing in recent years. The anticancer properties of natural compounds are related to the regulation of microRNA (miRNA) expression. Therefore, changing the profile of miRNAs with the use of natural products is very important in cancer treatment. However, the role of vulpinic acid and related miRNAs in breast cancer progression remains unknown. Vulpinic acid, methyl (as2E)-2-(3-hydroxy-5-oxo-4-phenylfuran-2-ylidene)-2 phenylacetate, is a natural product extracted from the lichen species and shows an anticancer effect on different cancer cells. Methods This study examines the effects of vulpinic acid on the miRNA levels of breast cancer (MCF-7) cells and its relationship with cell proliferation and apoptosis levels. The antiproliferative effect of vulpinic acid was screened against MCF-7 breast cancer cells and MCF-12A breast epithelial cells using the xCELLigence real-time cell analysis system. We analyzed the altered miRNA expression profile in MCF-7 breast cancer cells versus MCF-12A cells following their response to vulpinic acid through microarray analysis. The microarray analysis results were confirmed through quantitative real-time PCR and bioinformatics analysis. Results The results of the miRNA array and bioinformatic analyses demonstrated that 12 miRNAs were specifically responsive to vulpinic acid in MCF-7 breast cancer cells. This is the first study to reveal that vulpinic acid inhibits the expression of 12 miRNAs and suppresses breast cancer cell proliferation. The study also revealed that vulpinic acid may downregulate the expression of 12 miRNAs by repressing the FOXO-3 gene. The miRNA targets were mainly found to play a role in the apoptosis, cell cycle and MAPK pathways. Moreover, Bcl-2, Bax, procaspase-3 and procaspase-9 protein levels were assessed by western blot analysis for validation of apoptosis at the protein level. Conclusion This study revealed the molecular mechanisms of vulpinic acid on breast cancer and showed that vulpinic acid regulates apoptosis signaling pathways by decreasing the expression of miRNAs. The miRNA expression patterns illuminate the underlying effect of vulpinic acid in breast cancer treatment. Graphical Abstract

scholarly journals Capsaicin Potentiates Anticancer Drug Efficacy Through Autophagy-Mediated Ribophorin II Downregulation and Necroptosis in Oral Squamous Cell Carcinoma Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Ching Huang ◽  
Tien-Ming Yuan ◽  
Bang-Hung Liu ◽  
Kai-Li Liu ◽  
Chiung-Hua Wung ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Anticancer Drugs ◽  
Apoptotic Cell ◽  
Squamous Carcinoma ◽  
Chemotherapeutic Agents ◽  
Carcinoma Cells ◽  
Down Regulation ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma

The ability of capsaicin co-treatment to sensitize cancer cells to anticancer drugs has been widely documented, but the detailed underlying mechanisms remain unknown. In addition, the role of ribophorin II turnover on chemosensitization is still uncertain. Here, we investigated capsaicin-induced sensitization to chemotherapeutic agents in the human oral squamous carcinoma cell lines, HSC-3 and SAS. We found that capsaicin (200 μM) did not induce remarkable apoptotic cell death in these cell lines; instead, it significantly enhanced autophagy with a concomitant decrease of ribophorin II protein. This capsaicin-induced decrease in ribophorin II was intensified by the autophagy inducer, rapamycin, but attenuated by the autophagy inhibitors, ULK1 inhibitor and chloroquine, indicating that the autophagic process was responsible for the capsaicin-induced down-regulation of ribophorin II. Co-administration of capsaicin with conventional anticancer agents did, indeed, sensitize the cancer cells to these agents. In co-treated cells, the induction of apoptosis was significantly reduced and the levels of the necroptosis markers, phospho-MLKL and phospho-RIP3, were increased relative to the levels seen in capsaicin treatment alone. The levels of DNA damage response markers were also diminished by co-treatment. Collectively, our results reveal a novel mechanism by which capsaicin sensitizes oral cancer cells to anticancer drugs through the up-regulation of autophagy and down-regulation of ribophorin II, and further indicate that the induction of necroptosis is a critical factor in the capsaicin-mediated chemosensitization of oral squamous carcinoma cells to conventional anticancer drugs.

scholarly journals Flowers for cancer treatment: From beauty to duty

TAYACAJA ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 193-202
Author(s):  
Jorge L. Gutierrez-Pajares ◽  
Amr Abdelkhalek
Keyword(s):  
Side Effects ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Chemotherapeutic Drugs ◽  
Target Cancer

Cancer is a worldwide disease that affects millions of people every year. Although there are several approved chemotherapeutic drugs for cancer treatment, there is s constant search for new molecules. This search is supported by the need of new molecules that could target cancer cells specifically reducing side effects or that could act synergistically with approved anticancer drugs. In this review, research on flower extracts and flower-derived molecules is presented.

scholarly journals Nigericin decreases the viability of multidrug-resistant cancer cells and lung tumorspheres and potentiates the effects of cardiac glycosides

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769431 ◽  
Author(s):  
Juan Sebastian Yakisich ◽  
Neelam Azad ◽  
Vivek Kaushik ◽  
George A O’Doherty ◽  
Anand Krishnan V Iyer
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Multidrug Resistant ◽  
Culture Conditions ◽  
Chemotherapeutic Agents ◽  
Serum Starvation ◽  
Synthetic Analog ◽  
Antitumor Effects ◽  
Anticancer Effects

Multiple factors including tumor heterogeneity and intrinsic or acquired resistance have been associated with drug resistance in lung cancer. Increased stemness and the plasticity of cancer cells have been identified as important mechanisms of resistance; therefore, treatments targeting cancer cells independent of stemness phenotype would be much more effective in treating lung cancer. In this article, we have characterized the anticancer effects of the antibiotic Nigericin in cells displaying varying degrees of stemness and resistance to anticancer drugs, arising from (1) routine culture conditions, (2) prolonged periods of serum starvation. These cells are highly resistant to conventional anticancer drugs such as Paclitaxel, Hydroxyurea, Colchicine, Obatoclax, Wortmannin, and LY294002, and the multidrug-resistant phenotype of cells growing under prolonged periods of serum starvation is likely the result of extensive rewiring of signaling pathways, and (3) lung tumorspheres that are enriched for cancer stem-like cells. We found that Nigericin potently inhibited the viability of cells growing under routine culture conditions, prolonged periods of serum starvation, and lung tumorspheres. In addition, we found that Nigericin downregulated the expression of key proteins in the Wnt canonical signaling pathway such as LRP6, Wnt5a/b, and β-catenin, but promotes β-catenin translocation into the nucleus. The antitumor effects of Nigericin were potentiated by the Wnt activator HLY78 and by therapeutic levels of the US Food and Drug Administration–approved drug Digitoxin and its novel synthetic analog MonoD. We believe that Nigericin may be used in a co-therapy model in combination with other novel chemotherapeutic agents in order to achieve potent inhibition of cancers that display varying degrees of stemness, potentially leading to sustained anticancer effects.

scholarly journals Use ofClostridium perfringensEnterotoxin and the Enterotoxin Receptor-Binding Domain (C-CPE) for Cancer Treatment: Opportunities and Challenges

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Zhijian Gao ◽  
Bruce A. McClane
Keyword(s):  
Cancer Treatment ◽  
Cancer Cells ◽  
Receptor Binding ◽  
Membrane Surface ◽  
Gastrointestinal Diseases ◽  
Chemotherapeutic Agents ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Development Of Resistance ◽  
Domain I

Clostridium perfringensenterotoxin (CPE) causes the symptoms associated with several common gastrointestinal diseases. CPE is a 35 kDa polypeptide consisting of three structured domains, that is, C-terminal domain I (responsible for receptor binding), domain II (responsible for oligomerization and membrane insertion), and domain III (which may participate in physical changes when the CPE protein inserts into membranes). Native CPE binds to claudin receptors, which are components of the tight junction. The bound toxin then assembles into a hexameric prepore on the membrane surface, prior to the insertion of this oligomer into membranes to form an active pore. The toxin is especially lethal for cells expressing large amounts of claudin-3 or -4, which includes many cancer cells. Initial studies suggest that native CPE has potential usefulness for treating several cancers where claudin CPE receptors are overexpressed. However, some challenges with immunogenicity, toxicity, and (possibly) the development of resistance may need to be overcome. An alternative approach now being explored is to utilize C-CPE, which corresponds approximately to receptor binding domain I, to enhance paracellular permeability and delivery of chemotherapeutic agents against cancer cells. Alternatively, C-CPE fusion proteins may prove superior to use of native CPE for cancer treatment. Finally, C-CPE may have application for other medical treatments, including vaccination or increasing drug absorption. The coming years should witness increasing exploitation of this otherwise formidable toxin.

Hydrogen-bonded supramolecular micelle-mediated drug delivery enhances the efficacy and safety of cancer chemotherapy

2020 ◽  
Vol 11 (16) ◽  
pp. 2791-2798
Author(s):  
Chih-Chia Cheng ◽  
Ya-Ting Sun ◽  
Ai-Wei Lee ◽  
Shan-You Huang ◽  
Wen-Lu Fan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cancer Chemotherapy ◽  
Drug Uptake ◽  
Supramolecular Polymers ◽  
Efficacy And Safety ◽  
Spherical Micelles ◽  
Oppositely Charged ◽  
Hydrogen Bonded

Multiple hydrogen-bonded supramolecular polymers tend to form stable spherical micelles with oppositely charged anticancer drugs in biological environments, which improves cellular drug uptake and more effectively induces apoptosis in cancer cells.

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