Iron(III)-salophene catalyzes redox cycles that induce phospholipid peroxidation and deplete cancer cells of ferroptosis-protecting cofactors.

Ferroptosis, a lipid peroxidation-driven cell death program kept in check by glutathione peroxidase 4 and endogenous redox cycles, promises access to novel strategies for treating therapy-resistant cancers. Chlorido [N,N'-disalicylidene-1,2-phenylenediamine]iron (III) complexes (SCs) have potent anti-cancer properties by inducing ferroptosis, apoptosis, or necroptosis through still poorly understood molecular mechanisms. Here, we show that SCs preferentially induce ferroptosis over other cell death programs in triple-negative breast cancer cells (LC ≥ 0.

Cancer Stem Cells: What Do We Know about Them?

During past decades, survival rates in cancer patients have drastically improved due to the successful development of novel, promising chemical compounds and therapeutic schedules [...

Simvastatin is effective in killing the radioresistant breast carcinoma cells.

Background: Statins, small molecular 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are widely used to lower cholesterol levels in lipid-metabolism disorders. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer by increasing recurrence free survival. Unfortunately, the underlying mechanisms remain elusive.

Molecular heterogeneity in breast carcinoma cells with increased invasive capacities.

Background Metastatic progression of breast cancer is still a challenge in clinical oncology. Therefore, an elucidation how carcinoma cells belonging to different breast cancer subtypes realize their metastatic capacities is needed. The aim of this study was to elucidate a similarity of activated molecular pathways underlying an enhancement of invasiveness of carcinoma cells belonging to different breast carcinoma subtypes.

Targeting Cancer Stem Cells Pathways for the Effective Treatment of Cancer.

Resistance to chemotherapy and relapse are major hurdles for the effective treatment of cancer. Major reason for this is a small sub population of cancer stem cells (CSCs) and its microenvironment. CSCs are critical driving force for several types of cancer, such as gastric, colon, breast and many more.

Olaparib is effective in combination with, and as maintenance therapy after, first-line endocrine therapy in prostate cancer cells.

A number of prostate cancer (PCa)-specific genomic aberrations (denominated BRCAness genes) have been discovered implicating sensitivity to PARP inhibition within the concept of synthetic lethality. Recent clinical studies show favorable results for the PARP inhibitor olaparib used as single agent for treatment of metastatic castration-resistant PCa. Using 2D and 3D cell culture models mimicking the different treatment and progression stages of PCa, we evaluated a potential use for olaparib in combination with first-line endocrine treatments, androgen deprivation, and complete androgen blockade, and as a maintenance therapy following on from endocrine therapy.

Promising Targets in Anti-cancer Drug Development: Recent Updates.

Cancer is a multifactorial disease and its genesis and progression are extremely complex. The biggest problem in the anticancer drug development is acquiring of multidrug resistance and relapse. Classical chemotherapeutics directly target the DNA of the cell, while the contemporary anticancer drugs involve molecular-targeted therapy such as targeting the proteins possessing abnormal expression inside the cancer cells.

Mechanisms of Tubulin Binding Ligands to Target Cancer Cells: Updates on their Therapeutic Potential and Clinical Trials.

Background: A number of chemically diverse substances bind to the tubulin and inhibit cell proliferation by disrupting microtubule dynamics. There are four binding sites for the ligands binding to the tubulin; taxane/epothilone and laulimalide/peloruside binding ligands stabilize microtubule while vinca and colchicine binding site agents promote microtubule depolymerization. Most of the tubulin binding ligands disturb the tubulin-microtubule dynamic equilibrium but these may exhibit anticancer activities through different mechanisms.

Radiation resistance: Cancer stem cells (CSCs) and their enigmatic pro-survival signaling.

Despite the fact that radiation therapy is a highly effective therapeutic approach, a small intratumoral cell subpopulation known as "cancer stem cells" (CSCs) is radiation-resistant and possesses specific molecular properties protecting it against radiation-induced damage. The exact mechanisms of this radioresistance are still not fully elucidated, but they relate to these cells' enhanced DNA repair capacities and their low intracellular ROS concentrations, resulting from their up-regulation of ROS scavengers. The low ROS content is accompanied by disturbances in cell cycle regulation, so it can be assumed that either CSCs are quiescent or dormant themselves, or that this cell population consists of at least two cell subpopulations: the normally and the slowly proliferating cells (quiescent or dormant cells).

Proteomic approach to understand metastatic spread.

The majority of tumor-related deaths are due to metastasis. Despite the clinical importance of understanding metastasis, we lack knowledge of the molecular mechanisms underlying tumor cell spreading and cell survival far from the primary tumor. Elucidating the molecular characteristics of highly metastatic carcinoma cells would help identify biomarkers or therapeutic targets relevant to predicting or combatting metastasis, and for this the phenotype of metastatic cells could be much more important than their genotype.

Crosstalk between DNA repair and cancer stem cell (CSC) associated intracellular pathways.

DNA damaging agents (ionizing radiation and chemotherapeutics) are considered as most effective in cancer treatment. However, there is a subpopulation of carcinoma cells within the tumour demonstrating resistance to DNA damaging treatment approaches. It is suggested that limited tumour response to this kind of therapy can be associated with specific molecular properties of carcinoma stem cells (CSCs) representing the most refractory cell subpopulation.

Putative biomarkers and therapeutic targets associated with radiation resistance.

Radiation therapy plays an important role in the management of malignant tumors, however, the problem of radiation resistance resulting in tumor recurrences after treatment is still unsolved. The emergence of novel biomarkers to predict cancer cell insensitivity to ionizing radiation could help to improve therapy results in cancer patients receiving radiation therapy. The proteomic approach could be effectively used to identify proteins associated with cancer radiation resistance.

Proteomics of cancer stem cells.

Purpose: New understanding of cancer stem cell (CSC) biology continues to emerge due to development of novel methods in genomics and proteomics. Analysis of nucleic acids (RNA, DNA) is widely used to elucidate molecular perturbations in malignant tumors and carcinoma cells, however genome data do not reflect the functional activities of encoded proteins. Therefore proteome-based methods could enhance knowledge about deregulation of pathways as a result of altered expression and activities of proteins in CSC.

Profilin 1: do we have a novel proteome-found biomarker predicting response to anticancer therapy?

About three decades ago, profilin 1 was described as a 15 kDa small protein. It was later shown that profilin 1 is a tumor suppressor in human carcinomas. Recent proteome-based data additionally demonstrated that the levels of profilin 1 expression could help to predict malignant tumor aggressiveness, response to anticancer therapy and risk of recurrence development.

Radioresistant head and neck squamous cell carcinoma cells: intracellular signaling, putative biomarkers for tumor recurrences and possible therapeutic targets.

Purpose: Treatment of local and distant head and neck cancer recurrences after radiotherapy remains an unsolved problem. In order to identify potential targets for use in effective therapy of recurrent tumors, we have investigated protein patterns in radioresistant (FaDu-IRR and SCC25-IRR, "IRR cells") as compared to parental (FaDu and SCC25) head and neck carcinoma cells.

Methods And Materials: Radiation resistant IRR cells were derived from parental cells after repeated exposure to ionizing radiation 10 times every two weeks at a single dose of 10 Gy, resulting in a total dose of 100 Gy.