Research Progress in Flavonoids as Potential Anticancer Drug Including Synergy with Other Approaches

2020 ◽  
Vol 20 (20) ◽  
pp. 1791-1809 ◽  
Author(s):  
Yusuf Hussain ◽  
Suaib Luqman ◽  
Abha Meena
Keyword(s):  
Multidrug Resistance ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cell Signalling ◽  
Resistance Mechanisms ◽  
Research Progress ◽  
Potential Candidate ◽  
Proliferating Cells ◽  
Oncology Research

Background: In chemotherapy for cancer, conventional drugs aim to target the rapidly growing and dividing cells at the early stages. However, at an advanced stage, cancer cells become less susceptible because of the multidrug resistance and the recruitment of alternative salvage pathways for their survival. Besides, owing to target non-selectivity, healthy proliferating cells also become vulnerable to the damage. The combination therapies offered using flavonoids to cure cancer not only exert an additive effect against cancer cells by targetting supplementary cell carnage pathways but also hampers the drug resistance mechanisms. Thus, the review aims to discuss the potential and pharmacokinetic limitations of flavonoids in cancer treatment. Further successful synergistic studies reported using flavonoids to treat cancer has been described along with potential drug delivery systems. Methods: A literature search was done by exploring various online databases like Pubmed, Scopus, and Google Scholar with the specific keywords like “Anticancer drugs”, “flavonoids”, “oncology research”, and “pharmacokinetics”. Results: Dietary phytochemicals, mainly flavonoids, hinder cell signalling responsible for multidrug resistance and cancer progression, primarily targeting cancer cells sparing normal cells. Such properties establish flavonoids as a potential candidate for synergistic therapy. However, due to low absorption and high metabolism rates, the bioavailability of flavonoids becomes a challenge. Such challenges may be overcome using novel approaches like derivatization, and single or co-delivery nano-complexes of flavonoids with conventional drugs. These new approaches may improve the pharmacokinetic and pharmacodynamic of flavonoids. Conclusion: This review highlights the application of flavonoids as a potential anticancer phytochemical class in combination with known anti-cancer drugs/nanoparticles. It also discusses flavonoid’s pharmacokinetics and pharmacodynamics issues and ways to overcome such issues. Moreover, it covers successful methodologies employed to establish flavonoids as a safe and effective phytochemical class for cancer treatment.

Anticancer Activity of Diosgenin and its Semi-synthetic Derivatives: Role in Autophagy Mediated Cell Death and Induction of Apoptosis

2021 ◽  
Vol 21 ◽  
Author(s):  
Nivedita Bhardwaj ◽  
Nancy Tripathi ◽  
Bharat Goel ◽  
Shreyans K. Jain
Keyword(s):  
Cell Death ◽  
Cancer Treatment ◽  
Anticancer Activity ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Rational Approach ◽  
Potential Candidate ◽  
Potential Implication ◽  
Apoptosis Protein ◽  
Synthetic Derivatives

: During cancer progression, the unrestricted proliferation of cells is supported by the impaired cell death response provoked by certain oncogenes. Both autophagy and apoptosis are the signaling pathways of cell death, which are targeted for cancer treatment. Defects in apoptosis result in reduced cell death and ultimately tumor progression. The tumor cells lacking apoptosis phenomena are killed by ROS- mediated autophagy. The autophagic programmed cell death requires apoptosis protein for inhibiting tumor growth; thus, the interconnection between these two pathways determines the fate of a cell. The cross-regulation of autophagy and apoptosis is an important aspect to modulate autophagy, apoptosis and to sensibilise apoptosis-resistant tumor cells under metabolic stress and might be a rational approach for drug designing strategy for the treatment of cancer. Numerous proteins involved in autophagy have been investigated as the druggable target for anticancer therapy. Several compounds of natural origin have been reported, to control autophagy activity through the PI3K/Akt/mTOR key pathway. Diosgenin, a steroidal sapogenin has emerged as a potential candidate for cancer treatment. It induces ROS-mediated autophagy, inhibits PI3K/Akt/mTOR pathway, and produces cytotoxicity selectively in cancer cells. This review aims to focus on optimal strategies using diosgenin to induce apoptosis by modulating the pathways involved in autophagy regulation and its potential implication in the treatment of various cancer. The discussion has been extended to the medicinal chemistry of semi-synthetic derivatives of diosgenin exhibiting anticancer activity.

scholarly journals Mechanisms of Multidrug Resistance in Cancer Chemotherapy

2020 ◽  
Vol 21 (9) ◽  
pp. 3233 ◽  
Author(s):  
Karol Bukowski ◽  
Mateusz Kciuk ◽  
Renata Kontek
Keyword(s):  
Multidrug Resistance ◽  
Cancer Treatment ◽  
Anticancer Agents ◽  
Alkylating Agents ◽  
Gene Mutations ◽  
Resistance Mechanisms ◽  
Chemotherapeutic Agents ◽  
Future Research ◽  
Repair Capacity ◽  
Dna Repair Capacity

Cancer is one of the main causes of death worldwide. Despite the significant development of methods of cancer healing during the past decades, chemotherapy still remains the main method for cancer treatment. Depending on the mechanism of action, commonly used chemotherapeutic agents can be divided into several classes (antimetabolites, alkylating agents, mitotic spindle inhibitors, topoisomerase inhibitors, and others). Multidrug resistance (MDR) is responsible for over 90% of deaths in cancer patients receiving traditional chemotherapeutics or novel targeted drugs. The mechanisms of MDR include elevated metabolism of xenobiotics, enhanced efflux of drugs, growth factors, increased DNA repair capacity, and genetic factors (gene mutations, amplifications, and epigenetic alterations). Rapidly increasing numbers of biomedical studies are focused on designing chemotherapeutics that are able to evade or reverse MDR. The aim of this review is not only to demonstrate the latest data on the mechanisms of cellular resistance to anticancer agents currently used in clinical treatment but also to present the mechanisms of action of novel potential antitumor drugs which have been designed to overcome these resistance mechanisms. Better understanding of the mechanisms of MDR and targets of novel chemotherapy agents should provide guidance for future research concerning new effective strategies in cancer treatment.

Is metronomic vinorelbine (mVRL) able to inhibit both HUVEC and triple-negative breast cancer (TNBC) cells? The proof-of-concept VICTOR-0 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14014-e14014
Author(s):  
Maria Grazia Cerrito ◽  
Davide Pelizzoni ◽  
Marco De Giorgi ◽  
Nunzio Digiacomo ◽  
Marialuisa Lavitrano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Umbilical Vein ◽  
Metastatic Breast ◽  
Proof Of Concept ◽  
Proliferating Cells ◽  
Drug Concentrations

e14014 Background: TNBC represents an important clinical challenge because of poor prognosis. One of the emerging strategy to achieve disease control while reducing toxicity is metronomic chemotherapy (mCHT) which targets the endothelial cells (ECs) and inhibits the tumor growth. mVRL is a promising option in patients (pts) with metastatic breast cancer (MBC), resulting in a median PFS of 7.7 months and median OS of 15.9. To better explain the effect of mVRL we studied the effects of metronomic doses of VRL in in vitro models and compared them with standard doses of the same drug. Methods: Cell viability and cytotoxicity assays were performed on TNBC cancer cells (MDA-MB-231) and Human Umbilical Vein Endothelial Cells (HUVEC). Cell lines were exposed to different concentration (0,01nM-1mM) of VRL for 4 and 96 h. To simulate the metronomic dosing schedule, we replaced the drug-enriched medium every 24h, while to simulate the conventional administration protocol (sCHT) cells were exposed to VRL for 4h, then the medium was changed and replaced with fresh medium without drug every 24 h. The IC50was calculated by non-linear regression fit of the mean values of data obtained in triplicate experiments. Results: A significant anti-proliferative activity was observed on both HUVEC and MDA cells treated with VRL in mCHT as compared to sCHT protocol (see Table). These lower drug concentrations did not have remarkable effects on cell death. Conversely, the higher dose utilized in sCHT produced important cell death in MDA as well as in HUVEC, even if in vivo, the higher dose of drug inducing the largest apoptosis of cancer cells also affectd healthy proliferating cells causing toxicity. Our findings suggest that mCHT inhibited the proliferation of both endothelial and tumour cells and can block cancer progression with minor side effects. Conclusions: This study provides the proof-of-concept that metronomic doses of VRL, but not the standard ones, are able to inhibit, at the same concentration, both the ECs and the TNBC cells. The clinical trial TEMPO-BREAST, which compares metronomic vs standard VRL, is ongoing in MBC pts. [Table: see text]

scholarly journals Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1346 ◽  
Author(s):  
Naffouje ◽  
Grover ◽  
Yu ◽  
Sendilnathan ◽  
Wolfe ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Cancer Progression ◽  
De Novo ◽  
Malignant Tumors ◽  
Inosine Monophosphate Dehydrogenase ◽  
Variable Response ◽  
Purine Nucleotides ◽  
Proliferating Cells ◽  
Anti Cancer ◽  
Impdh Inhibitors

The purine nucleotides ATP and GTP are essential precursors to DNA and RNA synthesis and fundamental for energy metabolism. Although de novo purine nucleotide biosynthesis is increased in highly proliferating cells, such as malignant tumors, it is not clear if this is merely a secondary manifestation of increased cell proliferation. Suggestive of a direct causative effect includes evidence that, in some cancer types, the rate-limiting enzyme in de novo GTP biosynthesis, inosine monophosphate dehydrogenase (IMPDH), is upregulated and that the IMPDH inhibitor, mycophenolic acid (MPA), possesses anti-tumor activity. However, historically, enthusiasm for employing IMPDH inhibitors in cancer treatment has been mitigated by their adverse effects at high treatment doses and variable response. Recent advances in our understanding of the mechanistic role of IMPDH in tumorigenesis and cancer progression, as well as the development of IMPDH inhibitors with selective actions on GTP synthesis, have prompted a reappraisal of targeting this enzyme for anti-cancer treatment. In this review, we summarize the history of IMPDH inhibitors, the development of new inhibitors as anti-cancer drugs, and future directions and strategies to overcome existing challenges.

LPS/TLR4 pathways in breast cancer: insights into cell signalling

2021 ◽  
Vol 28 ◽  
Author(s):  
Rizwana Afroz ◽  
E M Tanvir ◽  
Mousumi Tania ◽  
Junjiang Fu ◽  
Mohammad Amjad Kamal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Vaccine Development ◽  
Cell Signalling ◽  
Signal Transduction Pathway ◽  
Cancer Cell Proliferation ◽  
Invasion And Metastasis ◽  
Oncology Research ◽  
Tlr4 Activation

Background: Cancer cells are usually recognized as foreign particles by the immune cells. Mounting evidences suggest important link between toll like receptors (TLRs) and carcinogenesis. This review article focused on the role of TLRs, especially TLR4 in breast cancer. Methods: Research data on TLRs and cancer was explored in PubMed, Scopus, Google Scholar, and reviewed. Although some pioneer works are referenced, papers published in last ten years were mostly cited. Results: TLRs are widely investigated pattern recognition receptors (PRR), and TLR4 is the most studied TLRs, implicated with occurrence of several types of cancers including breast cancer. TLR4 activation occurs via the binding of its ligand lipopolysaccharide (LPS), a component of the outer membrane of gram negative bacteria. Upon LPS binding, TLR4 dimerizes and recruits downstream signalling and/or adapter molecules leading to gene expression related to cancer cell proliferation, survival, invasion, and metastasis. Although LPS/TLR4 signalling seems a single signal transduction pathway, the TLR4 activation results in the activation of multiple diverse intracellular networks with huge cellular responses in both immune and cancer cells. The role of TLR4 in growth, invasion and metastasis of breast cancer is attracting huge attention in oncology research. Several clinical and preclinical studies utilize both TLR4 agonists and antagonists as treatment option for cancer therapy either as monotherapy or adjuvants for vaccine development. Conclusion: This review narrates the role of LPS/TLR4 signalling in breast cancer development and future prospective for targeting LPS/TLR4 axis in the treatment of breast cancer.

scholarly journals hPEBP4 Resists TRAIL-induced Apoptosis of Human Prostate Cancer Cells by Activating Akt and Deactivating ERK1/2 Pathways

2006 ◽  
Vol 282 (7) ◽  
pp. 4943-4950 ◽  
Author(s):  
Hongzhe Li ◽  
Xiaojian Wang ◽  
Nan Li ◽  
Jianming Qiu ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Potential Candidate ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Efficient Treatment ◽  
Akt Activation ◽  
Du145 Cells ◽  
Induced Apoptosis

The treatment options available for prostate cancer are limited because of its resistance to therapeutic agents. Thus, a better understanding of the underlying mechanisms of the resistance of prostate cancer will facilitate the discovery of more efficient treatment protocols. Human phosphatidylethanolamine-binding protein 4 (hPEBP4) is recently identified by us as an anti-apoptotic molecule and a potential candidate target for breast cancer treatment. Here we found the expression levels of hPEBP4 were positively correlated with the severity of clinical prostate cancer. Furthermore, hPEBP4 was not expressed in TRAIL-sensitive DU145 prostate cancer cells, but was highly expressed in TRAIL-resistant LNCaP cells, which show highly activated Akt. Interestingly, hPEBP4 overexpression in TRAIL-sensitive DU145 cells promoted Akt activation but inhibited ERK1/2 activation. The hPEBP4-overexpressing DU145 cells became resistant to TRAIL-induced apoptosis consequently, which could be reversed by PI3K inhibitors. In contrast, silencing of hPEBP4 in TRAIL-resistant LNCaP cells inhibited Akt activation but increased ERK1/2 activation, resulting in their sensitivity to TRAIL-induced apoptosis that was restored by the MEK1 inhibitor. Therefore, hPEBP4 expression in prostate cancer can activate Akt and deactivate ERK1/2 signaling, leading to TRAIL resistance. We also demonstrated that hPEBP4-mediated resistance to TRAIL-induced apoptosis occurred downstream of caspase-8 and at the level of BID cleavage via the regulation of Akt and ERK pathways, and that hPEBP4-regulated ERK deactivation was upstream of Akt activation in prostate cancer cells. Considering that hPEBP4 confers cellular resistance to TRAIL-induced apoptosis and is abundantly expressed in poorly differentiated prostate cancer, silencing of hPEBP4 suggests a promising approach for prostate cancer treatment.

scholarly journals Sorcin, a Calcium Binding Protein Involved in the Multidrug Resistance Mechanisms in Cancer Cells

Molecules ◽  
2014 ◽  
Vol 19 (9) ◽  
pp. 13976-13989 ◽  
Author(s):  
Gianni Colotti ◽  
Elena Poser ◽  
Annarita Fiorillo ◽  
Ilaria Genovese ◽  
Valerio Chiarini ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Calcium Binding ◽  
Binding Protein ◽  
Resistance Mechanisms ◽  
Calcium Binding Protein

scholarly journals Magnetic Compression of Tumor Spheroids Increases Cell Proliferation In Vitro and Cancer Progression In Vivo

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 366
Author(s):  
Gaëtan Mary ◽  
Brice Malgras ◽  
Jose Efrain Perez ◽  
Irène Nagle ◽  
Nathalie Luciani ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Peritoneal Cancer Index ◽  
Colon Cancer Cells ◽  
Tumor Spheroids ◽  
Proliferating Cells ◽  
The Impact

A growing tumor is submitted to ever-evolving mechanical stress. Endoscopic procedures add additional constraints. However, the impact of mechanical forces on cancer progression is still debated. Herein, a set of magnetic methods is proposed to form tumor spheroids and to subject them to remote deformation, mimicking stent-imposed compression. Upon application of a permanent magnet, the magnetic tumor spheroids (formed from colon cancer cells or from glioblastoma cells) are compressed by 50% of their initial diameters. Such significant deformation triggers an increase in the spheroid proliferation for both cell lines, correlated with an increase in the number of proliferating cells toward its center and associated with an overexpression of the matrix metalloproteinase−9 (MMP−9). In vivo peritoneal injection of the spheroids made from colon cancer cells confirmed the increased aggressiveness of the compressed spheroids, with almost a doubling of the peritoneal cancer index (PCI), as compared with non-stimulated spheroids. Moreover, liver metastasis of labeled cells was observed only in animals grafted with stimulated spheroids. Altogether, these results demonstrate that a large compression of tumor spheroids enhances cancer proliferation and metastatic process and could have implications in clinical procedures where tumor compression plays a role.

scholarly journals Nanoparticles for Cancer Therapy: Current Progress and Challenges

2021 ◽  
Author(s):  
Shreelaxmi Gavas ◽  
Sameer Quazi ◽  
Tomasz Karpiński
Keyword(s):  
Multidrug Resistance ◽  
Cancer Treatment ◽  
Resistance Mechanisms ◽  
Multi Drug Resistance ◽  
Cancer Therapies ◽  
Therapeutic Implications ◽  
Current Perspective ◽  
Reduced Toxicity

Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1-100nm) can be used in the treatment of cancer owing to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nano-formulations have created brand new perspectives for cancer treatment. However, a majority of the research is limited to in vivo and in vitro studies, and the number of nano-drugs that are approved has not much amplified over the years. In this review, we discuss numerous types of nanoparticles, targeting mechanisms along with approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation.

Sign in / Sign up

Export Citation Format

Share Document