Differential antiangiogenic and anticancer activities of the active metabolites of ginsenoside Rg3.

Background: Epimers of ginsenoside Rg3 (Rg3) have a low bioavailability and are prone to deglycosylation, which produces epimers of ginsenoside Rh2 (S-Rh2 and R-Rh2) and protopanaxadiol (S-PPD and R-PPD). The aim of this study was to compare the efficacy and potency of these molecules as anti-cancer agents.

Methods: Crystal violet staining was used to study the anti-proliferatory action of the molecules on a human epithelial breast cancer cell line, MDA-MB-231, and human umbilical vein endothelial cells (HUVEC) and compare their potency.

Unravelling the Glioblastoma Tumour Microenvironment: Can Aptamer Targeted Delivery Become Successful in Treating Brain Cancers?

The key challenges to treating glioblastoma multiforme (GBM) are the heterogeneous and complex nature of the GBM tumour microenvironment (TME) and difficulty of drug delivery across the blood-brain barrier (BBB). The TME is composed of various neuronal and immune cells, as well as non-cellular components, including metabolic products, cellular interactions, and chemical compositions, all of which play a critical role in GBM development and therapeutic resistance. In this review, we aim to unravel the complexity of the GBM TME, evaluate current therapeutics targeting this microenvironment, and lastly identify potential targets and therapeutic delivery vehicles for the treatment of GBM.

Natural Blockers of PD-1/PD-L1 Interaction for the Immunotherapy of Triple-Negative Breast Cancer-Brain Metastasis.

The limited treatment options for triple-negative breast cancer with brain metastasis (TNBC-BM) have left the door of further drug development for these patients wide open. Although immunotherapy via monoclonal antibodies has shown some promising results in several cancers including TNBC, it cannot be considered the most effective treatment for brain metastasis. This is due to the protective role of the blood-brain barrier (BBB) which limits the entrance of most drugs, especially the bulky ones such as antibodies, to the brain.

A Flow Cytometry-based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer.

A key challenge in developing an anticancer aptamer is to efficiently determine the selectivity and specificity of the developed aptamer to the target protein. Due to its several advantages over monoclonal antibodies, aptamer development has gained enormous popularity among cancer researchers. Systematic evolution of ligands by exponential enrichment (SELEX) is the most common method of developing aptamers specific for proteins of interest.

Cytotoxic effects of aptamer-doxorubicin conjugates in an ovarian cancer cell line.

Despite medical advances in treatment strategies over the past 30-years, epithelial ovarian cancer (EOC) continues to be defined by poor patient survival rates and aggressive, drug resistant relapse. Traditional approaches to cancer chemotherapy are typically limited by severe off-target effects on healthy tissue and aggressive drug-resistant recurrence. Recent shifts towards targeted therapies offer the possibility of circumventing the obstacles experienced by these treatments.

Modelling of mass transport and distribution of aptamer in blood-brain barrier for tumour therapy and cancer treatment.

The blood-brain barrier (BBB) is a strong barrier against the entrance of drugs, which has made brain cancer treatment a major challenge. We have previously shown that targeting transferrin receptors using aptamers increased brain drug delivery. To get a better understanding of this phenomenon, in the present article, a mathematical model based on the finite element method was developed accounting for the fluid flow and mass transport of the aptamer molecule inside an 8 µm capillary vessel across a 14 µm blood-brain barrier domain.

Triple-negative breast cancer brain metastasis: An update on druggable targets, current clinical trials, and future treatment options.

The key challenges with the treatment of triple-negative breast cancer brain metastasis (TNBC-BM) are the lack of any targeted therapy and difficulties associated with drug delivery to the brain. These add to the high toxicity profile of existing treatments and the poor outcomes for patient. In this review, we introduce current drugs based on their molecular targets and look to improve brain drug delivery using more efficient and promising drug delivery systems.

Future of PD-1/PD-L1 axis modulation for the treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has the worst prognosis among the subtypes of breast cancer, with no targeted therapy available. Immunotherapy targeting programmed cell death protein-1 (PD-1) and its ligand (PD-L1) has resulted in some promising outcomes in cancer patients. The common treatments are monoclonal antibodies (mAbs).

Anti-Cancer Effects of an Optimised Combination of Ginsenoside Rg3 Epimers on Triple Negative Breast Cancer Models.

Key problems of chemotherapies, as the mainstay of treatment for triple-negative breast cancer (TNBC), are toxicity and development of tumour resistance. Using response surface methodology, we previously optimised the combination of epimers of ginsenoside Rg3 (Rg3) for anti-angiogenic action. Here, we show that the optimised combination of 50 µM SRg3 and 25 µM RRg3 (C3), derived from an RSM model of migration of TNBC cell line MDA-MB-231, inhibited migration of MDA-MB-231 and HCC1143, in 2D and 3D migration assays ( < 0.

In Vitro Synergistic Inhibition of HT-29 Proliferation and 2H-11 and HUVEC Tubulogenesis by Bacopaside I and II Is Associated with Ca Flux and Loss of Plasma Membrane Integrity.

We previously showed how triterpene saponin bacopaside (bac) II, purified from the medicinal herb , induced cell death in colorectal cancer cell lines and reduced endothelial cell migration and tube formation, and further demonstrated a synergistic effect of a combination of bac I and bac II on the inhibition of breast cancer cell line growth. Here, we assessed the effects of bac I and II on the colorectal cancer HT-29 cell line, and mouse (2H-11) and human umbilical vein endothelial cell (HUVEC) lines, measuring outcomes including cell viability, proliferation, migration, tube formation, apoptosis, cytosolic Ca levels and plasma membrane integrity. Combined bac I and II, each applied at concentrations below IC values, caused a synergistic reduction of the viability and proliferation of HT-29 and endothelial cells, and impaired the migration of HT-29 and tube formation of endothelial cells.

Anti-Angiogenic Properties of Ginsenoside Rg3 Epimers: In Vitro Assessment of Single and Combination Treatments.

Tumour angiogenesis plays a key role in tumour growth and progression. The application of current anti-angiogenic drugs is accompanied by adverse effects and drug resistance. Therefore, finding safer effective treatments is needed.

Anti-Angiogenic Properties of Ginsenoside Rg3.

Ginsenoside Rg3 (Rg3) is a member of the ginsenoside family of chemicals extracted from . Like other ginsenosides, Rg3 has two epimers: 20(S)-ginsenoside Rg3 (SRg3) and 20(R)-ginsenoside Rg3 (RRg3). Rg3 is an intriguing molecule due to its anti-cancer properties.

Druggable Molecular Targets for the Treatment of Triple Negative Breast Cancer.

Breast cancer (BC) is still the most common cancer among women worldwide. Amongst the subtypes of BC, triple negative breast cancer (TNBC) is characterized by deficient expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. These patients are therefore not given the option of targeted therapy and have worse prognosis as a result.

Bacopasides I and II Act in Synergy to Inhibit the Growth, Migration and Invasion of Breast Cancer Cell Lines.

Bacopaside (bac) I and II are triterpene saponins purified from the medicinal herb . Previously, we showed that bac II reduced endothelial cell migration and tube formation and induced apoptosis in colorectal cancer cell lines. The aim of the current study was to examine the effects of treatment with combined doses of bac I and bac II using four cell lines representative of the breast cancer subtypes: triple negative (MDA-MB-231), estrogen receptor positive (T47D and MCF7) and human epidermal growth factor receptor 2 (HER2) positive (BT-474).

Stereoselective Anti-Cancer Activities of Ginsenoside Rg3 on Triple Negative Breast Cancer Cell Models.

Ginsenoside Rg3 (Rg3) has two epimers, 20(S)-ginsenoside Rg3 (SRg3) and 20(R)-ginsenoside Rg3 (RRg3), and while Rg3 itself has been reported to have anti-cancer properties, few studies have been reported on the anti-cancer effects of the different epimers. The aim was to investigate the stereoselective effects of the Rg3 epimers on triple negative breast cancer (TNBC) cell lines, tested using cell-based assays for proliferation, apoptosis, cell cycle arrest, migration and invasion. Molecular docking showed that Rg3 interacted with the aquaporin 1 (AQP1) water channel (binding score -9.

Bumetanide-Derived Aquaporin 1 Inhibitors, AqB013 and AqB050 Inhibit Tube Formation of Endothelial Cells through Induction of Apoptosis and Impaired Migration In Vitro.

AqB013 and AqB050 compounds inhibit aquaporin 1 (AQP1), a dual water and ion channel implicated in tumour angiogenesis. We tested AqB013 and AqB050 either as monotherapy or in combination on tube formation of murine endothelial cells (2H-11 and 3B-11) and human umbilical vascular endothelial cells (HUVECs). The mechanism underlying their anti-tubulogenic effect was explored by examining cell viability, induction of apoptosis and migration using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2-tetrazolium (MTS) assay, Annexin V/propidium iodide apoptosis assay and scratch wound assay.

Reduced aquaporin-1 transcript expression in colorectal carcinoma is associated with promoter hypermethylation.

Aquaporin-1 (AQP1) is a homo-tetrameric transmembrane protein that facilitates rapid movement of water and ions across cell membranes. The clinical significance of AQP1 expression in colorectal carcinoma (CRC) is controversial. The aim of this study was to investigate the prognostic significance of AQP1 transcript expression and the association between expression and promoter methylation in normal colonic mucosa, CRC tissues and cell lines.

Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer.

Breast cancer is still one of the most prevalent cancers and a leading cause of cancer death worldwide. The key challenge with cancer treatment is the choice of the best therapeutic agents with the least possible toxicities on the patient. Recently, attention has been drawn to herbal compounds, in particular ginsenosides, extracted from the root of the Ginseng plant.

Evaluation of Silibinin Effects on the Viability of HepG2 (Human hepatocellular liver carcinoma) and HUVEC (Human Umbilical Vein Endothelial) Cell Lines.

Human hepatocellular carcinoma is one of the most common recurrent malignancies since there is no effective therapy for it. Silibinin, a widely used drug and supplement for various liver disorders, demonstrated anti-cancer effects on human hepatocellular carcinoma, human prostate adenocarcinoma cells, human breast carcinoma cells, human ectocervical carcinoma cells, and human colon cancer cells. Considering the anti-hepatotoxic activity of silibinin and its strong preventive and anti-cancer efficacy against various epithelial cancers, we investigated the efficacy of silibinin against human HCC and HUVEC cell lines.

Effect of steroid and serum starvation on a human breast cancer adenocarcinoma cell line.

Breast cancer is one of the most frequent cancers in women. Although there are many treatment protocols for this disease, there are still many patients who do not respond satisfactorily to the current treatment protocols. A better understanding of the nature of the tumor cells might provide a guide for better therapeutic procedures.

Cellular glutathione level does not predict ovarian cancer cells' resistance after initial or repeated exposure to cisplatin.

Objective: Cisplatin resistance development is a major obstacle in ovarian cancer treatment. One of the most important mechanisms underlying cisplatin resistance is drug detoxification by glutathione. In the present study, the importance of initial or repeated exposure to cisplatin in glutathione dependent resistance was investigated.

Human Lung Carcinoma Reaction against Metabolic Serum Deficiency Stress.

Cancer treatment is still of the greatest challenges that health care providers and patients are facing. One of the unsolved problems in cancer treatment is cells' reaction to metabolic stress caused by harsh nutritional conditions around tumor. In order to be able to treat this disease properly, it is important to understand the true nature of the disease.

Cytotoxicity of selected novel chalcone derivatives on human breast, lung and hepatic carcinoma cell lines.

Cancer is considered as a challenging deathly disease and discovering or synthesis of new cytotoxic agents is a worldwide attempt. In this study, a group of recently synthesized chalcones, with the structure of 1,3-diarylprop-2-en-1-one having different COX-1 and/or COX-2 selectivities have been examined on human hepatocarcinoma (HepG2), lung carcinoma (A549), and breast adenocarcinoma (MCF-7) cell line, using Sulforhodamine B (SRB) assay. Briefly, cells were treated with 1-100 μM of each compound for 72, 96 and 168 hours.

FTIR-Microspectroscopy Detection of Metronidazole Teratogenic Effects on Mice Fetus.

Metronidazole is used to treat trichomoniasis, bacterial vaginosis, and other diseases. There are controversy aspects about its teratogenicity. A teratogenic agent can alter morphology or subsequent function of the fetus.