Revisiting the Anti-Cancer Toxicity of Clinically Approved Platinating Derivatives

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(23), С. 15410 - 15410

Опубликована: Дек. 6, 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, 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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Polymeric and non-polymeric oxaliplatin nanomedicine for cancer therapy: A comprehensive review

European Polymer Journal, Год журнала: 2024, Номер 208, С. 112870 - 112870

Опубликована: Фев. 23, 2024

Язык: Английский

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Protective effects of naringin against oxaliplatin-induced testicular damage in rats: Involvement of oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and histopathology.

PubMed, Год журнала: 2024, Номер 27(4), С. 466 - 474

Опубликована: Янв. 1, 2024

Oxaliplatin (OXL) is a platinum-based chemotherapeutic agent widely used in the treatment of colorectal cancer. Unfortunately, this important drug also causes unwanted side effects such as neuropathy, ototoxicity, and testicular toxicity. This study aimed to investigate possible protective naringin (NRG) against OXL-induced toxicity rats.

Язык: Английский

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New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(22), С. 13990 - 13990

Опубликована: Ноя. 13, 2022

There is new and increasing evidence from in vitro, vivo clinical studies implicating the pivotal role of iron associated metabolic pathways initiation, progression development cancer metastasis. New toxicity mechanisms pathways, as well genomic, transcription other factors, have been linked to many are related iron. Accordingly, a number targets for chelators identified characterized anticancer strategies, addition classical restriction of/reduction supply, inhibition transferrin delivery, ribonucleotide reductase DNA synthesis high antioxidant potential. The include removal excess iron-laden macrophages, which affects activity; modulation ferroptosis; ferritin control hyperferritinemia; hypoxia hypoxia-inducible factor (HIF); function molecular species such STEAP4 metalloreductase metastasis suppressor N-MYC downstream-regulated gene-1 (NDRG1); oxidative stress damage affecting mitochondrial function, etc. Many these new, but also previously known appear affect all stages cancer, drug resistance. Iron-chelating drugs especially deferiprone (L1), has shown recent fulfill multi-target above targets, proposed phase II trials patients. In contrast, lipophilic their complexes induction ferroptosis some refractory or recurring tumors resistance where effective treatments absent. need readdress therapy therapeutic strategies targeting multifactorial processes, including application multi-targeting involving iron-chelator complexes. protocols combinations with L1 chelating could increase activity, decrease metastasis, improve treatments, reduce overall survival

Язык: Английский

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Antidiabetic drug sitagliptin blocks cyclophosphamide cerebral neurotoxicity by activating Nrf2 and suppressing redox cycle imbalance, inflammatory iNOS/NO/NF-κB response and caspase-3/Bax activation in rats

International Immunopharmacology, Год журнала: 2023, Номер 116, С. 109816 - 109816

Опубликована: Фев. 11, 2023

Язык: Английский

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The Vital Role Played by Deferiprone in the Transition of Thalassaemia from a Fatal to a Chronic Disease and Challenges in Its Repurposing for Use in Non-Iron-Loaded Diseases

Pharmaceuticals, Год журнала: 2023, Номер 16(7), С. 1016 - 1016

Опубликована: Июль 18, 2023

The iron chelating orphan drug deferiprone (L1), discovered over 40 years ago, has been used daily by patients across the world at high doses (75–100 mg/kg) for more than 30 with no serious toxicity. level of safety and simple, inexpensive synthesis are some many unique properties L1, which played a major role in contribution transition thalassaemia from fatal to chronic disease. Other valuable clinical L1 relation pharmacology metabolism include: oral effectiveness, improved compliance compared prototype therapy subcutaneous deferoxamine; highly effective removal all iron-loaded organs, particularly heart, is target organ toxicity cause mortality thalassaemic patients; an ability achieve negative balance, completely remove excess iron, maintain normal stores rapid absorption stomach clearance body, allowing greater frequency repeated administration overall increased efficacy excretion, dependent on dose also concentration achieved site action; its cross blood–brain barrier treat malignant, neurological, microbial diseases affecting brain. Some differential pharmacological activity among generally shown absorption, distribution, metabolism, elimination, (ADMET) drug. Unique exhibited comparison other drugs include specific protein interactions antioxidant effects, such as transferrin lactoferrin; inhibition copper catalytic production free radicals, ferroptosis, cuproptosis; iron-containing proteins associated different pathological conditions. have attracted interest investigators repurposing use conditions, including cancer, neurodegenerative renal radical pathology, metal intoxication Fe, Cu, Al, Zn, Ga, In, U, Pu, diseases. Similarly, increase prospects wider optimizing therapeutic efforts fields medicine, synergies drugs.

Язык: Английский

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Vitamin e succinate-glycol chitosan modified copper ferrite nanocomposites for lung cancer: Targeted oxidative stress regulation induces cuproptosis and ferroptosis

Chemical Engineering Journal, Год журнала: 2024, Номер 493, С. 152408 - 152408

Опубликована: Май 22, 2024

Язык: Английский

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Anti-liver cancer effects and mechanisms and its application in nano DDS of polysaccharides: A review

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 279, С. 135181 - 135181

Опубликована: Авг. 30, 2024

Язык: Английский

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The mechanistic insights of the antioxidant Keap1-Nrf2 pathway in oncogenesis: a deadly scenario

Medical Oncology, Год журнала: 2023, Номер 40(9)

Опубликована: Июль 22, 2023

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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