Cisplatin in Liver Cancer Therapy

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 10858 - 10858

Опубликована: Июнь 29, 2023

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and often diagnosed at an unresectable advanced stage. Systemic chemotherapy as well transarterial chemoembolization (TACE) hepatic arterial infusion (HAIC) are used to treat HCC. TACE HAIC have long been standard of care for patients with HCC but limited treatment intrahepatic lesions. doxorubicin or chemohormonal therapy tamoxifen also considered, neither has demonstrated survival benefits. In HCC, cisplatin administered transhepatic arterially local treatment. Subsequently, cisplatin-refractory cases due drug resistance, a shift systemic different mechanism action expected produce new antitumor effects. Cisplatin tumors other than This review summarizes resistance describes major hepatobiliary cancers which anticancer agent, focus on

Язык: Английский

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Chloroquine and Chemotherapeutic Compounds in Experimental Cancer Treatment

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 945 - 945

Опубликована: Янв. 12, 2024

Chloroquine (CQ) and its derivate hydroxychloroquine (HCQ), the compounds with recognized ability to suppress autophagy, have been tested in experimental works clinical trials as adjuvant therapy for treatment of tumors different origin increase efficacy cytotoxic agents. Such a strategy can be effective overcoming resistance cancer cells standard chemotherapy or anti-angiogenic therapy. This review presents results combined application CQ/HCQ conventional drugs (doxorubicin, paclitaxel, platinum-based compounds, gemcitabine, tyrosine kinases PI3K/Akt/mTOR inhibitors, other agents) malignancies obtained experiments on cultured cells, animal xenografts models, few trials. The effects such an approach viability tumor growth, well autophagy-dependent -independent molecular mechanisms underlying cellular responses CQ/HCQ, are summarized. Although majority vitro vivo studies shown that effectively sensitize agents potential chemotherapy, often inconsistent. Nevertheless, pharmacological suppression autophagy remains promising tool increasing development more specific inhibitors is required.

Язык: Английский

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Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin

Foods, Год журнала: 2023, Номер 12(8), С. 1733 - 1733

Опубликована: Апрель 21, 2023

Quercetin is an antioxidant phytochemical which belongs to the natural flavonoids group. Recently, compound has been reported inhibit glutathione reductase responsible for replenishing reduced forms of and thus leads depletion, triggering cell death. In this study, we examined if quercetin sensitizes tumors oxaliplatin by inhibiting activity in human colorectal cancer cells, thereby facilitates apoptotic A combined treatment with was found synergistically activity, lower intracellular level, increase reactive oxygen species production, reduce viability, compared alone HCT116 cells. Furthermore, incorporation sulforaphane, recognized its ability scavenge glutathione, combination oxaliplatin, substantially suppressed tumor growth xenograft mouse model. These findings suggest that depletion sulforaphane could strengthen anti-cancer efficacy oxaliplatin.

Язык: Английский

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Metal-Based Complexes in Cancer

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 7289 - 7289

Опубликована: Апрель 14, 2023

Metal-based drugs have attracted growing interest in biomedicine [...]

Язык: Английский

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Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells

Cancers, Год журнала: 2023, Номер 15(21), С. 5136 - 5136

Опубликована: Окт. 25, 2023

High-grade serous ovarian cancer (HGSOC) accounts for 70% of cases, and the survival rate remains remarkably low due to lack effective long-term consolidation therapies. Clinical remission can be temporarily induced by platinum-based chemotherapy, but death subsequently results from extensive growth a platinum-resistant component tumor. This work explores novel treatment against HGSOC using gold complex auranofin (AF). AF primarily functions as pro-oxidant inhibiting thioredoxin reductase (TrxR), an antioxidant enzyme overexpressed in cancer. We investigated effect on TrxR activity various mechanisms cytotoxicity cells that are clinically sensitive or resistant platinum. In addition, we studied interaction between another pro-oxidant, L-buthionine sulfoximine (L-BSO), anti-glutathione (GSH) compound. demonstrated potently inhibited reduced vitality viability regardless their sensitivities showed induces accumulation reactive oxygen species (ROS), triggers depolarization mitochondrial membrane, kills inducing apoptosis. Notably, AF-induced cell was abrogated ROS-scavenger N-acetyl cysteine (NAC). lethality associated with activation caspases-3/7 generation DNA damage, effects were also prevented presence NAC. Finally, when L-BSO combined, observed synergistic cells, which mediated further increase ROS decrease levels GSH. summary, our support concept used alone combination kill sensitivity platinum, suggesting depletion antioxidants is efficient strategy mitigate course this disease.

Язык: Английский

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Revisiting the Anti-cancer Toxicity of Clinically Approved Platinating Derivatives

Опубликована: Ноя. 15, 2022

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They canonically known as DNA damage inducers; however, that is only one their mechanisms cytotoxicity. CDDP mediates its effects through damage-induced transcription inhibition apoptotic signalling. In addition, targets the endoplasmic reticulum (ER) to induce ER-stress, mitochondria via mitochondrial leading ROS production, plasma membrane cytoskeletal components. CP acts in similar fashion by inducing damage, ER stress. Additionally, also able upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on other hand, at first induces all same CP, yet it capable immunogenic cell death stress can decrease ribosome biogenesis nucleolar effects. this comprehensive review, we provide detailed action agents, going beyond nuclear include cytoplasmic impact within cancer cells. cover current clinical limitations, including side resistance.

Язык: Английский

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Ru(II) Complexes with 3,4-Dimethylphenylhydrazine: Exploring In Vitro Anticancer Activity and Protein Affinities

Biomolecules, Год журнала: 2025, Номер 15(3), С. 350 - 350

Опубликована: Фев. 28, 2025

Two new Ru(II) complexes, mononuclear [RuCl2(η6-p-cymene)(3,4-dmph-κN)] (1) and the binuclear complex [{RuCl(η6-p-cymene)}2(μ-Cl)(μ-3,4-dmph-κ2N,N′)]Cl (2; 3,4-dmph = 3,4-dimethylphenylhydrazine), are synthesized experimentally theoretically structurally characterized utilizing 1H 13C NMR FTIR spectroscopy, as well DFT calculations. Degradation product of 2, thus ([{RuCl(η6-p-cymene)}2(μ-Cl)(μ-3,4-dmph-κ2N,N′)][RuCl3(η6-p-cymene)] (2b) was with SC-XRD. In crystals 2b, cationic anionic parts interact through N-H...Cl hydrogen bridges. The spectrofluorimetric measurements proved spontaneity binding processes both complexes HSA. Spin probing EPR implied that 1 2 decreased amount bound 16-doxylstearate implicated their potential to bind HSA more strongly than spin probe. cytotoxicity assessment against MDA-MB-231 MIA PaCa-2 cancer cell lines demonstrated a clear dose-dependent decrease in viability no effect on healthy HS-5 cells. Determination malondialdehyde protein carbonyl concentrations indicated could offer protective antioxidant benefits specific contexts. Gel electrophoresis showed reduction MMP9 activity limiting cells’ invasion. annexin V/PI apoptotic assay results exhibit different selectivity towards A comparative molecular docking analysis binding, specifically targeting acetylcholinesterase (ACHE), matrix metalloproteinase-9 (MMP-9), human serum albumin (HSA), distinct interactions for each complex.

Язык: Английский

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Involvement of Ferroptosis Induction and Oxidative Phosphorylation Inhibition in the Anticancer-Drug-Induced Myocardial Injury: Ameliorative Role of Pterostilbene

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 3015 - 3015

Опубликована: Март 5, 2024

Patients with cancer die from cardiac dysfunction second only to the disease itself. Cardiotoxicity caused by anticancer drugs has been emphasized as a possible cause; however, details remain unclear. To investigate this mechanism, we treated rat cardiomyoblast H9c2 cells sunitinib, lapatinib, 5-fluorouracil, and cisplatin examine their effects. All increased ROS, lipid peroxide, iron (II) levels in mitochondria decreased glutathione peroxidase-4 GSH/GSSG ratio. Against background, mitochondrial accumulates through unregulated expression of haem oxygenase-1 ferrochelatase. Anticancer-drug-induced cell death was suppressed N-acetylcysteine, deferoxamine, ferrostatin, indicating ferroptosis. Anticancer drug treatment impairs DNA inhibits oxidative phosphorylation cells. Similar results were observed hearts cancer-free rats vitro. In contrast, pterostilbene inhibited induction ferroptosis rescued energy restriction induced both vitro vivo. These findings suggest that inhibition are mechanisms which cause myocardial damage. As ameliorates these mechanisms, it is expected have significant clinical applications.

Язык: Английский

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Functionalized Polymeric Micelles for Targeted Cancer Therapy: Steps from Conceptualization to Clinical Trials

Pharmaceutics, Год журнала: 2024, Номер 16(8), С. 1047 - 1047

Опубликована: Авг. 6, 2024

Cancer is still ranked among the top three causes of death in 30- to 69-year-old age group most countries and carries considerable societal macroeconomic costs that differ depending on cancer type, geography, patient gender. Despite advances several pharmacological approaches, lack stability specificity, dose-related toxicity, limited bioavailability chemotherapy (standard therapy) pose major obstacles treatment, with multidrug resistance being a driving factor failure. The past decades have been stage for intense research activity topic nanomedicine, which has resulted many nanotherapeutics reduced increased bioavailability, improved pharmacokinetics therapeutic efficacy employing smart drug delivery systems (SDDSs). Polymeric micelles (PMs) become an auspicious DDS medicinal compounds, used encapsulate hydrophobic drugs also exhibit substantial toxicity. Through preclinical animal testing, PMs pharmacokinetic profiles efficacy, resulting higher safety profile drugs. This review focuses are already clinical trials, traveling pathways from studies until introduction market.

Язык: Английский

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Equilibrium Studies on Pd(II)–Amine Complexes with Bio-Relevant Ligands in Reference to Their Antitumor Activity

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4843 - 4843

Опубликована: Март 2, 2023

This review article presents an overview of the equilibrium studies on Pd-amine complexes with bio-relevant ligands in reference to their antitumor activity. Pd(II) amines different functional groups, were synthesized and characterized many studies. The complex formation equilibria Pd(amine)2+ amino acids, peptides, dicarboxylic acids DNA constituents, extensively investigated. Such systems may be considered as one models for possible reactions occurring drugs biological systems. stability formed depends structural parameters ligands. evaluated speciation curves can help provide a pictorial presentation solutions pH values. data sulfur donor compared those reveal information regarding deactivation caused by donors. binuclear constituents was investigated support significance this class complexes. Most studied low dielectric constant medium, resembling that medium. Investigations thermodynamic species is exothermic.

Язык: Английский

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