Prospects for Prostate Cancer Chemotherapy: Cytotoxic Evaluation and Mechanistic Insights of Quinolinequinones with ADME/PK Profile.

The evaluation of in vitro biological activity of several previously reported quinolinequinones () against 60 human cancer cell lines (NCI-60) used by the National Cancer Institute's Developmental Therapeutics Program (DTP) contributed to our earlier research on possible anticancer and/or antibacterial agents. Of interest, NCI-60 screening revealed that two quinolinequinones ( and ) significantly reduced the proliferation of several cancer genotypes. Following the administration of a single dose and five additional doses, all quinolinequinones demonstrated a significant inhibitory effect on the growth of leukemia and other cancer cell lines.

Cytotoxic activity of quinolinequinones in cancer: In vitro studies, molecular docking, and ADME/PK profiling.

Lead molecules containing 1,4-quinone moiety are intriguing novel compounds that can be utilized to treat cancer owing to their antiproliferative activities. Nine previously reported quinolinequinones (AQQ1-9) were studied to better understand their inhibitory profile to produce potent and possibly safe lead molecules. The National Cancer Institute (NCI) of Bethesda chose all quinolinequinones (AQQ1-9) based on the NCI Developmental Therapeutics Program and tested them against a panel of 60 cancer cell lines.

Molecular Cardiotoxic Effects of Proteasome Inhibitors Carfilzomib and Ixazomib and Their Combination with Dexamethasone Involve Mitochondrial Dysregulation.

With the development and approval of new proteasome inhibitors, proteasome inhibition is increasingly recognized in cancer therapy. Besides successful anti-cancer effects in hematological cancers, side effects such as cardiotoxicity are limiting effective treatment. In this study, we used a cardiomyocyte model to investigate the molecular cardiotoxic mechanisms of carfilzomib (CFZ) and ixazomib (IXZ) alone or in combination with the immunomodulatory drug dexamethasone (DEX) which is frequently used in combination therapies in the clinic.

Ubiquitin proteasomal system is a potential target of the toxic effects of organophosphorus flame retardant triphenyl phosphate.

The consumption of the widely used flame retardant Triphenyl phosphate (TPP) is increasing. It is now frequently detected in the environment and also domestically. Although the possibility of dermal exposure to TPP is quite high, little is known about its potential molecular toxicity mechanisms.

and Study to Assess Toxic Mechanisms of Hybrid Molecules of Quinone-Benzocaine as Plastoquinone Analogues in Breast Cancer Cells.

We managed to obtain three different series of 2,3-dimethyl-1,4-benzoquinones, named nonhalogenated and halogenated (brominated and chlorinated) PQ analogues, the molecular hybridization strategy. Sixteen of eighteen hybrid molecules were selected by the National Cancer Institute (NCI) of Bethesda for their antiproliferative potential against the full NCI 60 cell line panel. The hybrid molecules (, , and ) showed good growth inhibition at 10 μM concentration, particularly against breast cancer cell lines.

Exploring the Anticancer Effects of Brominated Plastoquinone Analogs with Promising Cytotoxic Activity in MCF-7 Breast Cancer Cells via Cell Cycle Arrest and Oxidative Stress Induction.

Plastoquinone analogs are privileged structures among the known antiproliferative natural product-based compound families. Exploiting one of these analogs as a lead structure, we report the investigation of the brominated PQ analogs (BrPQ) in collaboration with the National Cancer Institute of Bethesda within the Developmental Therapeutics Program (DTP). These analogs exhibited growth inhibition in the micromolar range across leukemia, non-small cell lung cancer (EKVX, HOP-92, and NCI-H522), colon cancer (HCT-116, HOP-92), melanoma (LOX IMVI), and ovarian cancer (OVCAR-4) cell lines.

Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking.

In the present study, we designed and synthesized thiolated analogs () along with an extensive antimicrobial study. After the evaluation of the antibacterial and antifungal activity against various bacterial and fungal strains, we presented an initial structure-activity relationship study on these analogs. In particular, four thiolated analogs exhibited superior biological potency against some Gram-positive bacterial strains, including (ATCC 29213) and (ATCC 29212).

Zoledronic acid-induced oxidative damage and endoplasmic reticulum stress-mediated apoptosis in human embryonic kidney (HEK-293) cells.

Zoledronic acid, a nitrogen-containing bisphosphonate drug, is used for the treatment of osteoporosis, Paget's disease of bone, and tumor-induced osteolysis. Zoledronic acid has also gained a place in cancer treatment due to its cytotoxic and antiproliferative effects in many cancer cells. Although zoledronic acid is considered safe, kidney damage is still one of the concerns in therapeutic doses.

Determination of the Phototoxicity Potential of Commercially Available Tattoo Inks Using the 3T3-neutral Red Uptake Phototoxicity Test.

Objectives: Tattooing is an ancient practice and its popularity has been increasing in the recent years. After tattooing, complications may occur related to compose tattoo inks. In this study, the phototoxicity potential of the blue, red and black colors of the most commonly used three different commercially-available tattoo ink brands have been examined by performing 3T3-neutral red uptake (NRU) phototoxicity test.

Anticancer agents based on Plastoquinone analogs with N-phenylpiperazine: Structure-activity relationship and mechanism of action in breast cancer cells.

2,3-Dimethyl-1,4-benzoquinones named as Plastoquinone (PQ) analogs have antiproliferative activity and are promising new members of molecules that can be used to cope with cancer. In an attempt to develop effective and potentially safe antiproliferative agents, previously reported twelve Plastoquinone analogs (PQ1-12) have been obtained to understand their antiproliferative profile. All PQ analogs have been selected by the National Cancer Institute (NCI) of Bethesda based on the NCI Developmental Therapeutics Program and tested against the panel of 60 cancer cell lines.

Interactome analysis of Bag-1 isoforms reveals novel interaction partners in endoplasmic reticulum-associated degradation.

Bag-1 is a multifunctional protein that regulates Hsp70 chaperone activity, apoptosis, and proliferation. The three major Bag-1 isoforms have different subcellular localizations and partly non-overlapping functions. To identify the detailed interaction network of each isoform, we utilized mass spectrometry-based proteomics and found that interactomes of Bag-1 isoforms contained many common proteins, with variations in their abundances.

Mitochondrial dynamics imbalance and mitochondrial dysfunction contribute to the molecular cardiotoxic effects of lenvatinib.

Lenvatinib is a tyrosine kinase inhibitor (TKI) approved for the treatment of resistant differentiated thyroid cancer, advanced renal cell carcinoma, unresectable hepatocellular carcinoma, and endometrial carcinoma. Although it is successful in cancer treatment, it can cause life-threatening side effects such as cardiotoxicity. The molecular mechanism of cardiotoxicity caused by lenvatinib is not fully known.

assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells.

Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as "spice," "herbal incense," or "herbal blend," as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use.

Extended regorafenib treatment can be linked with mitochondrial damage leading to cardiotoxicity.

Regorafenib (RGF) has a great success in the treatment of colorectal cancer, gastrointestinal stromal tumours and hepatocellular carcinoma by inhibiting angiogenic, stromal and oncogenic kinases. However, RGF can induce life-threatening cardiotoxicity including hypertension and cardiac ischemia/infarction. The molecular mechanism of the adverse effects has not been elucidated.

Synergistic Induction of Apoptosis by Quercetin and Curcumin in Chronic Myeloid Leukemia (K562) Cells: II. Signal Transduction Pathways Involved.

Flavonoids are phenolic substances with chemo-preventive and chemotherapeutic properties. They are widely found in fruits and vegetables. The polyphenols quercetin and curcumin have antioxidant, anti-inflammatory, anti-carcinogenic, and pro-apoptotic properties.

Higher proteotoxic stress rather than mitochondrial damage is involved in higher neurotoxicity of bortezomib compared to carfilzomib.

Proteasome inhibitors have great success for their therapeutic potential against hematologic malignancies. First generation proteasome inhibitor bortezomib induced peripheral neuropathy is considered as a limiting factor in chemotherapy and its second-generation counterpart carfilzomib is associated with lower rates of neurotoxicity. The mitochondrial toxicity (mitotoxicity) hypothesis arises from studies with animal models of bortezomib induced peripheral neuropathy.

Celastrol pretreatment as a therapeutic option against cisplatin-induced nephrotoxicity.

Celastrol is a natural bioactive compound extracted from the medicinal plant Hook F. It exhibits immunosuppressive, anti-inflammatory, and antioxidant activities. Cisplatin is a commonly used chemotherapeutic drug in the treatment of a wide range of tumors.

Discovery of a new family of heterocyclic amine linked plastoquinone analogs for antimicrobial evaluation.

A series of aminobenzoquinones, denoted as PQ analogs (PQ1-13), were synthesized by employing a green methodology approach using water as solvent developed by Tandon et al. Subsequently, in vitro antimicrobial potential of all PQ analogs was evaluated in a panel of seven bacterial strains (three gram positive and four gram negative bacteria) and three fungi. The antifungal profile of all PQ analogs indicated that four analogs (while PQ2, PQ9, and PQ10 were effective against Candida tropicalis, PQ11 is effective against Candida albicans) have potent antifungal activity.

Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib.

The proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical applications.

Telomerase Reverse Transcriptase (TERT) Gene Variations and Susceptibility of Colorectal Cancer.

Aim: Colorectal cancer is the third most common cause of cancer-related mortality. Previous studies demonstrated increased telomerase activity in colorectal cancer tissue and suggested a prognostic value for patients with colorectal carcinoma. Telomerase reverse transcriptase (TERT), one of the main functional subunits of the telomerase, is an important factor in modulating telomerase activity, telomere length, and genomic stability.

Evaluation of DNA damage and DNA repair capacity in occupationally lead-exposed workers.

Occupational lead (Pb) exposure remains a significant concern for workers in Turkey. Health hazards of Pb exposure have been investigated in various test systems, but results regarding its potential genotoxic effects on exposed populations are contradictory. In this study, a control group and an exposed group were studied, each consisting of 25 male subjects.

VEGF gene polymorphisms and susceptibility to colorectal cancer.

Aims: Colorectal cancer (CRC) is the third most common cancer in the world and its etiology involves the interaction of genetic and environmental factors. New blood vessels form through a process called angiogenesis and have an essential role in tumor growth, progression, and metastasis of malignant tumors. The vascular endothelial growth factor (VEGF), one of the most important angiogenic factors, is a specific mitogen for vascular endothelial cells.