scholarly journals Enhanced Cancer Starvation Therapy Based on Glucose Oxidase/3-Methyladenine-Loaded Dendritic Mesoporous OrganoSilicon Nanoparticles

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1363
Author(s):  
Fan Wu ◽  
Yang Liu ◽  
Hui Cheng ◽  
Yun Meng ◽  
Jieyun Shi ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Glucose Oxidase ◽  
Adaptation Strategy ◽  
Cell Adaptation ◽  
Mesoporous Organosilica ◽  
Therapy Effect ◽  
Autophagy Inhibition ◽  
Tumor Growth Suppression

Cell autophagy is a well-known phenomenon in cancer, which limits the efficacy of cancer therapy, especially cancer starvation therapy. Glucose oxidase (GOx), which is considered as an attractive starvation reagent for cancer therapy, can effectively catalyze the conversion of glucose into gluconic acid and hydrogen peroxide (H2O2) in the presence of O2. However, tumor cells adapt to survive by inducing autophagy, limiting the therapy effect. Therefore, anti-cell adaptation via autophagy inhibition could be used as a troubleshooting method to enhance tumor starvation therapy. Herein, we introduce an anti-cell adaptation strategy based on dendritic mesoporous organosilica nanoparticles (DMONs) loaded with GOx and 3-methyladenine (3-MA) (an autophagy inhibition agent) to yield DMON@GOx/3-MA. This formulation can inhibit cell adaptative autophagy after starvation therapy. Our in vitro and in vivo results demonstrate that autophagy inhibition enhances the efficacy of starvation therapy, leading to tumor growth suppression. This anti-cell adaptation strategy will provide a new way to enhance the efficacy of starvation cancer therapy.

Enhanced Cancer Starvation Therapy via Autophagy Inhibition With a Functional Dendritic Mesoporous Organosilicon Nanoagent

2021 ◽  
Author(s):  
fan Wu ◽  
yang Liu ◽  
hui Cheng ◽  
yun Meng ◽  
yan Yi ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cancer Therapy ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Synergetic Effect ◽  
Therapy Effect ◽  
Autophagy Inhibition ◽  
Tumor Growth Suppression

Abstract Glucose oxidase (GOx) can effectively catalyze glucose intogluconic acid and hydrogen peroxide (H2O2) in the presence of O2, which is considered as an attractive starvation strategy for cancer therapy. However, the autophagy phenomenon protects tumor cells from starvation therapy, limiting the therapy effect, thus autophagy inhibition could be used as a troubleshooting method to enhance tumor starvation therapy. Herein, biodegradable dendritic mesoporous organosilicon nanoagent (DMON) was used as the nanocarrier to deliver GOx and 3-MA (an autophagyinhibition agent), designed as DMON@GOx/3-MA. T his formulation could have a synergetic effect on autophagy inhibition and starvation therapy. All in vitro and in vivo results demonstrated that autophagy inhibition obviously enhanced the efficacy of starvation therapy, leading to tumor growth suppression. Our strategy will provide a new way to enhance the efficacy of starvation cancer therapy.

scholarly journals YAP inhibits autophagy and promotes progression of colorectal cancer via upregulating Bcl-2 expression

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Lan Jin ◽  
Yunhe Chen ◽  
Dan Cheng ◽  
Zhikai He ◽  
Xinyi Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Transcriptional Coactivator ◽  
Inhibitory Protein ◽  
Potential Therapeutic Target ◽  
Related Cell ◽  
Autophagy Inhibition

AbstractColorectal cancer (CRC) is one of the most aggressive and lethal cancers. The role of autophagy in the pathobiology of CRC is intricate, with opposing functions manifested in different cellular contexts. The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor-suppressor pathway, functions as an oncoprotein in a variety of cancers. In this study, we found that YAP could negatively regulate autophagy in CRC cells, and consequently, promote tumor progression of CRC in vitro and in vivo. Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.

scholarly journals The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Fangfang Tao ◽  
Yanrong Zhang ◽  
Zhiqian Zhang
Keyword(s):  
Cancer Therapy ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Redox Status ◽  
Cancer Therapies ◽  
Bioactive Components ◽  
Atp Production

Mitochondria are highly dynamic double-membrane organelles which play a well-recognized role in ATP production, calcium homeostasis, oxidation-reduction (redox) status, apoptotic cell death, and inflammation. Dysfunction of mitochondria has long been observed in a number of human diseases, including cancer. Targeting mitochondria metabolism in tumors as a cancer therapeutic strategy has attracted much attention for researchers in recent years due to the essential role of mitochondria in cancer cell growth, apoptosis, and progression. On the other hand, a series of studies have indicated that traditional medicinal herbs, including traditional Chinese medicines (TCM), exert their potential anticancer effects as an effective adjunct treatment for alleviating the systemic side effects of conventional cancer therapies, for reducing the risk of recurrence and cancer mortality and for improving the quality of patients’ life. An amazing feature of these structurally diverse bioactive components is that majority of them target mitochondria to provoke cancer cell-specific death program. The aim of this review is to summarize the in vitro and in vivo studies about the role of these herbs, especially their bioactive compounds in the modulation of the disturbed mitochondrial function for cancer therapy.

scholarly journals Folate-Functionalized Mesoporous Hollow SnO2 Nanofibers as a Targeting Drug Carrier to Improve the Antitumor Effect of Paclitaxel for Liver Cancer Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Huiling Lv ◽  
Chao Wu ◽  
Xuan Liu ◽  
Andi Bai ◽  
Yue Cao ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Liver Cancer ◽  
Drug Carrier ◽  
In Vitro Release ◽  
Hollow Structure ◽  
Amorphous State ◽  
Outer Diameter ◽  
Drug Delivery Carrier

In this study, we prepared PTX-loaded mesoporous hollow SnO2 nanofibers conjugated with folic acid (SFNFP) for liver cancer therapy. According to SEM and TEM characterization, SFNF showed a mesoporous hollow structure. The average outer diameter was 200 nm, and the wall thickness was 50 nm. The DSC and XRD study showed that PTX in the channels of nanofibers was present in an amorphous state. The in vitro release experiments demonstrated that SFNF could efficiently improve the dissolution rate of PTX. Both in vitro cell experiments and in vivo antitumor experiments showed that SFNFP could efficiently inhibit the growth of liver cancer cells. Therefore, SFNF is a promising targeting antitumor drug delivery carrier.

scholarly journals Numerical Investigation of Ferrofluid Preparation during In-Vitro Culture of Cancer Therapy for Magnetic Nanoparticle Hyperthermia

Sensors ◽  
2021 ◽  
Vol 21 (16) ◽  
pp. 5545 ◽  
Author(s):  
Izaz Raouf ◽  
Piotr Gas ◽  
Heung Soo Kim
Keyword(s):  
Numerical Model ◽  
Cancer Therapy ◽  
Magnetic Nanoparticle ◽  
Research Work ◽  
Thermal Response ◽  
Linear Response Theory ◽  
Novel Approach ◽  
Magnetic Nanoparticle Hyperthermia

Recently, in-vitro studies of magnetic nanoparticle (MNP) hyperthermia have attracted significant attention because of the severity of this cancer therapy for in-vivo culture. Accurate temperature evaluation is one of the key challenges of MNP hyperthermia. Hence, numerical studies play a crucial role in evaluating the thermal behavior of ferrofluids. As a result, the optimum therapeutic conditions can be achieved. The presented research work aims to develop a comprehensive numerical model that directly correlates the MNP hyperthermia parameters to the thermal response of the in-vitro model using optimization through linear response theory (LRT). For that purpose, the ferrofluid solution is evaluated based on various parameters, and the temperature distribution of the system is estimated in space and time. Consequently, the optimum conditions for the ferrofluid preparation are estimated based on experimental and mathematical findings. The reliability of the presented model is evaluated via the correlation analysis between magnetic and calorimetric methods for the specific loss power (SLP) and intrinsic loss power (ILP) calculations. Besides, the presented numerical model is verified with our experimental setup. In summary, the proposed model offers a novel approach to investigate the thermal diffusion of a non-adiabatic ferrofluid sample intended for MNP hyperthermia in cancer treatment.

scholarly journals Targeting Sphingolipids for Cancer Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Osmel Companioni ◽  
Cristina Mir ◽  
Yoelsis Garcia-Mayea ◽  
Matilde E. LLeonart
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Cancer Therapy ◽  
Preclinical Studies ◽  
Hepatic Toxicity ◽  
Multiple Cancers ◽  
Extensive Class ◽  
Effective Drugs

Sphingolipids are an extensive class of lipids with different functions in the cell, ranging from proliferation to cell death. Sphingolipids are modified in multiple cancers and are responsible for tumor proliferation, progression, and metastasis. Several inhibitors or activators of sphingolipid signaling, such as fenretinide, safingol, ABC294640, ceramide nanoliposomes (CNLs), SKI-II, α-galactosylceramide, fingolimod, and sonepcizumab, have been described. The objective of this review was to analyze the results from preclinical and clinical trials of these drugs for the treatment of cancer. Sphingolipid-targeting drugs have been tested alone or in combination with chemotherapy, exhibiting antitumor activity alone and in synergism with chemotherapy in vitro and in vivo. As a consequence of treatments, the most frequent mechanism of cell death is apoptosis, followed by autophagy. Aslthough all these drugs have produced good results in preclinical studies of multiple cancers, the outcomes of clinical trials have not been similar. The most effective drugs are fenretinide and α-galactosylceramide (α-GalCer). In contrast, minor adverse effects restricted to a few subjects and hepatic toxicity have been observed in clinical trials of ABC294640 and safingol, respectively. In the case of CNLs, SKI-II, fingolimod and sonepcizumab there are some limitations and absence of enough clinical studies to demonstrate a benefit. The effectiveness or lack of a major therapeutic effect of sphingolipid modulation by some drugs as a cancer therapy and other aspects related to their mechanism of action are discussed in this review.

Plant derived secondary metabolites in cancer therapy: actions, applications, and future prospective of dietaryflavonol (quercetin)

2019 ◽  
Vol 1 (6) ◽  
pp. 135-143
Author(s):  
Krishnagowdu Saravanan ◽  
Jayachandran Halka ◽  
Kumaresan Kowsalya ◽  
Muthukrishnan Arun
Keyword(s):  
Cancer Therapy ◽  
Secondary Metabolites ◽  
Anticancer Agents ◽  
Higher Plants ◽  
Lung Tumor ◽  
Chemical Constituents ◽  
Food Additives ◽  
Antioxidant Agents

Higher plants are prominent sources for several bioactive chemical constituents (secondary metabolites) who include photochemical, flavoring agents, fragrant molecules, and food additives. According to WHO estimates, it has been reported that more than 80% of population in developing countries prefer these natural bioactive active compounds for their primary health requirement. At present, conventional chemotherapy is constrained due to the nonselective toxicity to human organs and their usage is limited now a days. In a recent survey, more than 60% of cancer patients have been preferring adjuvant phototherapy along with chemotherapy. Thus, photochemical are being widely used as anticancer agents to target specific pathological pathways underlying cancer with low toxic profiles and side effects. These photochemical are cost-effective and easily accessible to the public to treat cancer diseases. These bioactive photochemical are meticulously belongs to secondary metabolites such as alkaloids, flavonoids, polyphenols.Among them, the flavonoids are polyphenolic substances, which are found in all parts of the plant such as flowers, fruits, leaves, roots, seeds, and bark. They possess high medicinal properties like being anti-cancer, anti-hypertensive, anti-inflammatory, anti-obesity, anti-malarial, antioxidant agents. Quercetin is major flavones associated with a profound antioxidant and medicinal property to prevent the oxidation of lipids in vitro and in vivo, and also exhibits direct proapoptotic effects on tumor cells. This compound has proven efficacy in targeting several cancer cells of breast, colon, prostate, ovarian, and lung tumor in vitro. The present review focuses on the effect of quercetin in cancer therapy.

PEGylated liposomes as an emerging therapeutic platform for oral nanomedicine in cancer therapy: in vitro and in vivo assessment

2020 ◽  
Vol 303 ◽  
pp. 112649 ◽  
Author(s):  
Archu Singh ◽  
Yub Raj Neupane ◽  
Sadat Shafi ◽  
Bharti Mangla ◽  
Kanchan Kohli
Keyword(s):  
Cancer Therapy ◽  
Pegylated Liposomes ◽  
Therapeutic Platform ◽  
In Vivo Assessment

scholarly journals Pharmacophore hybridisation and nanoscale assembly to discover self-delivering lysosomotropic new-chemical entities for cancer therapy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhao Ma ◽  
Jin Li ◽  
Kai Lin ◽  
Mythili Ramachandran ◽  
Dalin Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Self Assembly ◽  
The Self ◽  
Single Drug ◽  
Drug Nanoparticles ◽  
Lysosomal Dysfunction ◽  
New Chemical Entities ◽  
Autophagy Inhibition

Abstract Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here we propose a self-delivering one-component new-chemical-entity nanomedicine (ONN) strategy to improve cancer therapy through incorporation of the self-assembly principle into drug design. A lysosomotropic detergent (MSDH) and an autophagy inhibitor (Lys05) are hybridised to develop bisaminoquinoline derivatives that can intrinsically form nanoassemblies. The selected BAQ12 and BAQ13 ONNs are highly effective in inducing lysosomal disruption, lysosomal dysfunction and autophagy blockade and exhibit 30-fold higher antiproliferative activity than hydroxychloroquine used in clinical trials. These single-drug nanoparticles demonstrate excellent pharmacokinetic and toxicological profiles and dramatic antitumour efficacy in vivo. In addition, they are able to encapsulate and deliver additional drugs to tumour sites and are thus promising agents for autophagy inhibition-based combination therapy. Given their transdisciplinary advantages, these BAQ ONNs have enormous potential to improve cancer therapy.

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