Plant Polyphenolic Compounds Potentiates Therapeutic Efficiency of Anticancer Chemotherapeutic Drugs: A Review.

2020 ◽  
Vol 20 ◽  
Author(s):  
Lokanatha Oruganti ◽  
Balaji Meriga
Keyword(s):  
Cancer Therapy ◽  
Adverse Effects ◽  
Combination Therapy ◽  
Synergistic Effects ◽  
Chemotherapeutic Agents ◽  
Polyphenolic Compounds ◽  
Systematic Research ◽  
Chemotherapeutic Drugs ◽  
Pharmaceutical Ingredients ◽  
Potential Synergy

Background: Scientific research continues to develop more efficacious drugs to treat and cure cancer, the dreadful disease threatening the human race. Chemotherapy is an essential means in cancer therapy, however, plant drugs having pharmacological safety, can be used alone or as additions to current chemotherapeutic agents to enhance therapeutic efficacy and minimize chemotherapy-induced adverse effects. Objective: A combination therapy where the synergistic effect on multiple targets is possible has gained significance, because since a one-drug one-target approach fails to yield the desired therapeutic effect. Therefore, a detailed description of important plant polyphenolic compounds with anticancer activity and their role in potentiating chemotherapeutic efficiency of existing anticancer drugs is provided in this review. Systematically screening combinations of active pharmaceutical ingredients for potential synergy with plant compounds may be especially valuable in cancer therapy. Methodology: We extensively have gone through reviews and research articles available in the literature. We made use of databases such as Google Scholar, Research Gate, PubMed, Science Direct, etc. The following keywords were used in our literature search: “Chemotherapy, drug development, cancer drugs, plant-derived polyphenolics, synergistic studies, combination therapy, diagnosis and genetics.” Conclusion: Systematic research studies on screening combinations of plant phytochemicals with potential chemotherapeutic pharmaceuticals throws light on their synergistic effects, mechanisms of actions paving the way to develop more efficient anticancer therapeutics to treat and cure the cancer menace, to nullify chemotherapy-induced adverse effects and our review substantially contributes in this direction.

Time and Dose Dependent Synergism Between Conventional Cytostatics and the p53-Modulating Small Molecule PRIMA-Meth in p53 Mutated Leukemic Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5029-5029
Author(s):  
Dina Ali ◽  
Christer Paul ◽  
S.ören Lehmann
Keyword(s):  
Synergistic Effect ◽  
Cell Survival ◽  
Synergistic Effects ◽  
Chemotherapeutic Agents ◽  
Stress Factors ◽  
Leukemic Cells ◽  
Chemotherapeutic Drugs ◽  
Cytostatic Drugs ◽  
Simultaneous Exposure ◽  
Survival Percentage

Abstract Background: P53 deletions and mutations can be found in 5 to 15% of patients with acute myeloid leukemia and in about 50% of all human cancers. Mutations in the p15 gene are associated with resistance to cancer chemotherapy. Furthermore, p53 is involved in the induction of apoptosis in response to many cellular stress factors. P53 mutations in AML are associated to poor prognosis and a decreased sensitivity to chemotherapeutic drugs. PRIMA-meth (APR-246) belongs to a new generation of the compounds proved to restore the function of p53. It has been shown that PRIMA-1 meth works synergistically with some cancer chemotherapeutic agents through mutant p53-dependent pathway. Aim: To identify a novel effective regimen for AML patients by incorporating PRIMA-meth. The study was performed in vitro in order to evaluate a regimen that can exert the most pronounced synergistic effect when combining PRIMA-meth with conventional chemotherapeutic drugs. Materials and Methods: After optimizing the doses of the drugs and the exposure time, cells were incubated with daunorubicin (0.01μM) cytarabine (0.5μM) and fludarabine (20μM) alone and in combination with PRIMA-meth (5, 10 and15μM). Three different timing schedules of the exposure were tested; one with 24 hours pretreatment with PRIMA-meth, one with 24 hours pretreatment with the cytostatic drugs and one with simultaneuous incubation of PRIMA-meth in combination with the cytostatics. After 96 hours of incubation, the cell viability was analyzed by a bioluminescence assay measuring ATP levels. Each experiment was done in triplicate. Results: Pre-incubation for 24 hours in PRIMA-meth exerted synergistic effects at 15μM in combination with all three tested drugs (table 1). This effect was superior to the combination effect seen when cells were pre-incubated with the cytostatic drugs where synergism was seen only with fludarabine. In the 24 hour pretreatment regimens, more potent synergism was found with fludarabine in combination with the higher PRIMA-meth concentrations (10μM and 15μM) irrespectively which drug was added first. Generally, the higher the prima-meth concentration, the better the response to combination therapy. With simultaneous exposure, synergism was found only with fludarabine in combination with PRIMA-meth at the highest concentration. N.B: Values represent ratio values between actual cell survival percentage and expected cell survival percentage (synergistic effect< or =0,8; additive effect >0,8<1,2). In conclusion, PRIMA-meth can exert synergistic effects in combination with conventional chemotherapeutic drugs in p53 mutated AML cells. Synergism could be seen with fludarabine irrespectively of the timing of the exposure whereas synergism with daunorubicin and cytarabine was seen only when preincubating cells with PRIMA-meth. Synergisms were seen when using PRIMA-meth at higher concentrations. This suggests that similar combinations are promising and should be used for combination treatments in clinical trials.

scholarly journals Evaluation of the Synergistic Antibacterial Effects of Fosfomycin in Combination with Selected Antibiotics against Carbapenem–Resistant Acinetobacter baumannii

2021 ◽  
Vol 14 (3) ◽  
pp. 185
Author(s):  
Ozioma F. Nwabor ◽  
Pawarisa Terbtothakun ◽  
Supayang P. Voravuthikunchai ◽  
Sarunyou Chusri
Keyword(s):  
Combination Therapy ◽  
Synergistic Effects ◽  
Cost Effective ◽  
Experimental Models ◽  
Chemotherapeutic Agents ◽  
Multi Drug Resistance ◽  
Bacterial Cells ◽  
Fold Reduction ◽  
Time Kill

The spread of multi-drug resistant (MDR) pathogens and the lagging pace in the development of novel chemotherapeutic agents warrant the use of combination therapy as a reliable, cost-effective interim option. In this study, the synergistic effects of fosfomycin in combination with other antibiotics were assessed. Of the 193 isolates, 90.6% were non-susceptible to fosfomycin, with minimum inhibitory concentrations (MICs) of ≥128 µg/mL. Antibacterial evaluation of fosfomycin-resistant isolates indicated multi-drug resistance to various antibiotic classes. Combinations of fosfomycin with 12 commonly used antibiotics synergistically inhibited most fosfomycin-resistant isolates. The fractional inhibitory concentration index indicated that combining fosfomycin with either aminoglycosides, glycylcyclines, fluoroquinolones, or colistin resulted in 2- to 16-fold reduction in the MIC of fosfomycin. Time-kill kinetics further confirmed the synergistic bactericidal effects of fosfomycin in combination with either amikacin, gentamicin, tobramycin, minocycline, tigecycline, or colistin, with more than 99.9% reduction in bacterial cells. Fosfomycin-based combination therapy might serve as an alternative option for the treatment of MDR A. baumannii. Further steps including in vivo efficacy and toxicity in experimental models of infection are required prior to clinical applications.

Cardiotoxicity of Cancer Therapy

2005 ◽  
Vol 23 (30) ◽  
pp. 7685-7696 ◽  
Author(s):  
Justin D. Floyd ◽  
Duc T. Nguyen ◽  
Raymond L. Lobins ◽  
Qaiser Bashir ◽  
Donald C. Doll ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Adverse Effects ◽  
Antineoplastic Agents ◽  
The United States ◽  
Chemotherapeutic Agents ◽  
Therapeutic Modalities ◽  
Normal Tissues ◽  
Neoplastic Processes ◽  
Multiple Organs ◽  
Number Of Patients

Because cancer is a leading cause of mortality in the United States, the number of therapeutic modalities available for the treatment of neoplastic processes has increased. This has resulted in a large number of patients being exposed to a wide variety of cancer therapy. Historically, it has been well recognized that antineoplastic agents may have adverse effects on multiple organs and normal tissues. The most commonly associated toxicities occur in tissues composed of rapidly dividing cells and may spontaneously reverse with minimal long-term toxicity. However, the myocardium consists of cells that have limited regenerative capability, which may render the heart susceptible to permanent or transient adverse effects from chemotherapeutic agents. Such toxicity encompasses a heterogeneous group of disorders, ranging from relatively benign arrhythmias to potentially lethal conditions such as myocardial ischemia/infarction and cardiomyopathy. In some instances, the pathogenesis of these toxic effects has been elucidated, whereas in others the precise etiology remains unknown. We review herein the various syndromes of cardiac toxicity that are reported to be associated with antineoplastic agents and discuss their putative mechanisms and treatment.

scholarly journals Chemotherapy Based on Supramolecular Chemistry: A Promising Strategy in Cancer Therapy

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 292 ◽  
Author(s):  
Fahmy ◽  
Brüßler ◽  
Alawak ◽  
El-Sayed ◽  
Bakowsky ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Adverse Effects ◽  
Self Assembly ◽  
Targeted Delivery ◽  
Water Solubility ◽  
Chemotherapeutic Agents ◽  
Supramolecular Systems ◽  
Promising Strategy ◽  
Selective Targeting ◽  
Cancerous Cells

Chemotherapeutic agents are considered one of the strategies in treating cancer. However, their use is faced by many challenges, such as poor water solubility leading to poor bioavailability and non-selective targeting of cancerous cells leading to diminished therapeutic actions and systemic adverse effects. Many approaches were adopted to overcome these drawbacks and to achieve the targeted delivery of the chemotherapeutic agents to the cancerous cells while minimizing adverse effects. Recently, supramolecular systems such as macrocycles have gained attention in the field of cancer therapy for being able to encapsulate different anticancer drugs via either host-guest complexation or self-assembly leading to a myriad of advantages. This review highlights the most recent studies concerned with the design of such novel systems for cancer therapy.

Landscape of Combination Therapy – Which Way Forward? Proceedings of the Satellite Symposium Held at the ESH European Meeting on Hypertension and Cardiovascular Protection, 27 April 2012, London

2012 ◽  
Vol 8 (3) ◽  
pp. 192
Author(s):  
Patricia Fonseca ◽  
Anna F Dominiczak ◽  
Stephen Harrap ◽  
◽  
◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Risk ◽  
Combination Therapy ◽  
Enzyme Inhibitor ◽  
Synergistic Effects ◽  
Term Treatment ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Hypertensive Patients ◽  
Long Term Treatment

Early combination therapy is more effective for hypertension control in high-risk patients than monotherapy, and current guidelines recommend the use of either an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) for first-line therapy in patients younger than 55 years. Recent evidence shows that ACEIs reduce mortality, whereas ARBs show no apparent benefit despite their blood pressure lowering action. However, it is important to consider which blood pressure parameters should be targeted given that different drugs have distinct effects on key parameters. Remarkably, a high percentage of hypertensive patients whose treatment has brought these parameters within target ranges still remain at high risk of cardiovascular disease due to additional risk factors. Combination therapy with synergistic effects on blood pressure and metabolic control should thus be considered for the long-term treatment of hypertensive patients with co-morbid conditions.

KIDNEY INJURY IN CANCER THERAPY

2018 ◽  
Vol 22 (5) ◽  
pp. 17-24 ◽  
Author(s):  
E. V. Burnasheva ◽  
Y. V. Shatokhin ◽  
I. V. Snezhko ◽  
A. A. Matsuga
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Cancer Therapy ◽  
Cancer Patients ◽  
Cytotoxic Effect ◽  
Tumor Lysis Syndrome ◽  
Kidney Injury ◽  
Chemotherapeutic Agents ◽  
Oxygen Intermediates ◽  
Circulating Blood Volume

Кidney injury is a frequent and significant complication of cancer and cancer therapy. The kidneys are susceptible to injury from malignant infiltration, damage by metabolites of malignant cells, glomerular  injury, nephrotoxic drugs including chemotherapeutic agents. Also  bone marrow transplantation complications, infections with immune  suppression (including septicemia), tumor lysis syndrome should be  taken into account. Chemotherapeutic agents are a common cause  of acute kidney injury but can potentially lead to chronic kidney  disease development in cancer patients. This article summarizes risk  factors of acute kidney injury in cancer patients. Risk factors are  divided into two groups. The systemic are decrease of total  circulating blood volume, infiltration of kidney tissue by tumor cells,  dysproteinemia, electrolyte disturbances. The local (renal) risk  factors are microcirculation disturbances, drugs biotransformation  with formation of reactive oxygen intermediates, high concentration of nephrotoxic agents in proximal tubules and its  sensitivity to ischemia. Drug-related risk factors include: drugs  combination with cytotoxic effect high doses long term use necessity, direct cytotoxic effect of not only chemotherapeutic agents but also its metabolites, mean solubility forming intratubular  precipitates. Early diagnosis, timely prevention and treatment of  these complications provide significantly improve nononcologic results of treatment.

Discovery of an Unexpected Similarity in Ligand Binding Between BRD4 and PPARγ

2019 ◽  
Author(s):  
Lina Humbeck ◽  
Jette Pretzel ◽  
Saskia Spitzer ◽  
Oliver Koch
Keyword(s):  
Cancer Therapy ◽  
Drug Targets ◽  
Synergistic Effects ◽  
Complex Structure ◽  
Peroxisome Proliferator ◽  
Resistance Development ◽  
Peroxisome Proliferator Activated Receptor ◽  
Starting Point ◽  
Fundamental Research ◽  
Important Drug

Knowledge about interrelationships between different proteins is crucial in fundamental research for the elucidation of protein networks and pathways. Furthermore, it is especially critical in chemical biology to identify further key regulators of a disease and to take advantage of polypharmacology effects. A comprehensive scaffold-based analysis uncovered an unexpected relationship between bromodomain-containing protein 4 (BRD4) and peroxisome-proliferator activated receptor gamma (PPARγ). They are both important drug targets for cancer therapy and many more important diseases. Both proteins share binding site similarities near a common hydrophobic subpocket which should allow the design of a polypharmacology-based ligand targeting both proteins. Such a dual-BRD4-PPARγ-modulator could show synergistic effects with a higher efficacy or delayed resistance development in, for example, cancer therapy. Thereon, a complex structure of sulfasalazine was obtained that involves two bromodomains and could be a potential starting point for the design of a bivalent BRD4 inhibitor.

Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Side Effects ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Anticancer Drugs ◽  
Chemotherapeutic Agents ◽  
Oxidation Reactions ◽  
Hybrid Compounds ◽  
Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

Lipid-based Nanoplatforms in Cancer Therapy: Recent Advances and Applications

2020 ◽  
Vol 20 (4) ◽  
pp. 271-287 ◽  
Author(s):  
Kuldeep Rajpoot
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Adverse Effects ◽  
Targeted Drug Delivery ◽  
Tumor Therapy ◽  
Cancer Therapies ◽  
Medication Delivery ◽  
Lipid Nanocarriers ◽  
Targeted Drug ◽  
Drug Nanocarriers

Though modern available cancer therapies are effective, they possess major adverse effects, causing non-compliance to patients. Furthermore, the majority of the polymeric-based medication platforms are certainly not universally acceptable, due to their several restrictions. With this juxtaposition, lipid-based medication delivery systems have appeared as promising drug nanocarriers to replace the majority of the polymer-based products because they are in a position to reverse polymer as well as, drug-associated restrictions. Furthermore, the amalgamation of the basic principle of nanotechnology in designing lipid nanocarriers, which are the latest form of lipid carriers, has tremendous chemotherapeutic possibilities as tumor-targeted drug-delivery pertaining to tumor therapy. Apart from this, it is reported that nearly 40% of the modern medication entities are lipophilic. Moreover, research continues to be efficient in attaining a significant understanding of the absorption and bioavailability of the developed lipids systems.

Cytoprotective Agents to Avoid Chemotherapy Induced Sideeffects on Normal Cells: A Review

2019 ◽  
Vol 19 (10) ◽  
pp. 765-781
Author(s):  
Seema Rohilla ◽  
Harish Dureja ◽  
Vinay Chawla
Keyword(s):  
Adverse Effects ◽  
Anticancer Agents ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Vital Role ◽  
Normal Cells ◽  
Normal Tissues ◽  
Organ Specific ◽  
Delay In Treatment

Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.

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