RESUMEN
Apoptosis has traditionally been regarded as the desired cell death pathway activated by chemotherapeutic drugs due to its controlled and non-inflammatory nature. However, recent discoveries of alternative cell death pathways have paved the way for immune-stimulatory treatment approaches in cancer. Ferroptosis (dependent on iron) and cuproptosis (dependent on copper) hold promise for selective cancer cell targeting and overcoming drug resistance. Copper ionophores and iron-bearing nano-drugs show potential for clinical therapy as single agents and as adjuvant treatments. Here we review up-to-date evidence for the involvement of metal ion-dependent cell death pathways in the cytotoxicity of classical chemotherapeutic agents (alkylating agents, topoisomerase inhibitors, antimetabolites, and mitotic spindle inhibitors) and their combinations with cuproptosis and ferroptosis inducers, indicating the prospects, advantages, and obstacles of their use.
Asunto(s)
Antineoplásicos , Cobre , Ferroptosis , Neoplasias , Ferroptosis/efectos de los fármacos , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Cobre/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Hierro/metabolismo , Animales , Transducción de Señal/efectos de los fármacos , Muerte Celular/efectos de los fármacosRESUMEN
For decades, common chemotherapeutic drugs have been established to trigger apoptosis, the preferred immunologically "silent" form of cell death. The primary objective of this review was to show that various FDA-approved chemotherapeutic drugs, including cisplatin, cyclosporine, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, paclitaxel, or vinblastine can trigger necroptosis and pyroptosis. We aimed to provide the advantages and disadvantages of the induction of the given type of cell death by chemotherapeutical agents. Moreover, we give a short overview of the molecular mechanism of each type of cell death and indicate the existing crosstalks between cell death types. Finally, we provide a comparison of cell death types to facilitate the exploration of cell death types induced by other chemotherapeutical agents. Understanding the cell death pathway induced by a drug can lessen side effects and assist the discovery of new combinations with synergistic effects and low systemic toxicity.
Asunto(s)
Necroptosis , Piroptosis , Humanos , Apoptosis , Muerte Celular , Paclitaxel/farmacología , Paclitaxel/uso terapéuticoRESUMEN
Due to the richness of bioactive substances and easy accessibility, sea-buckthorn can be an ingredient of currently popular functional food supporting anti-cancer therapy. Low-polarity fractions from fruit (OL), twigs (GL) and leaves (LL) were investigated. Compared to the previous scientific reports a more detailed analysis of the chemical composition of individual fractions was performed. Cytotoxicity of low-polarity fractions has been investigated and activity compared in human tumor and normal cells cultured in vitro. The genotoxicity and pro-apoptotic properties of low-polarity fractions were also followed on selected cell lines that had proved to be the most sensitive. In the proposed research model being tested, low-polarity fractions act cytotoxically, even 3 times more strongly in cancer cells than normal ones. Measurement of caspase 3/7 activity indicated that cell death occurs through apoptosis. Furthermore, high concentrations of low-polarity fractions have moderate genotoxic properties. Data obtained on the biological properties of low-polarity fractions from sea-buckthorn show that these fractions can potentially support cancer cells elimination. Phytotochemical analysis indicates the key role of the triterpenoids in this process.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Elaeagnaceae , Neoplasias/tratamiento farmacológico , Extractos Vegetales/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Daño del ADN , Elaeagnaceae/química , Células HCT116 , Células HT29 , Humanos , Células MCF-7 , Neoplasias/metabolismo , Neoplasias/patología , Células PC-3 , Extractos Vegetales/aislamiento & purificaciónRESUMEN
Many patients being treated for cancer use dietary supplements, particularly antioxidants, in the hope of reducing the toxicity of chemotherapy or radiotherapy. However, clinicians should advise their patients against using antioxidant dietary supplements during chemotherapy. Irinotecan (CPT-11) is a common chemotherapeutic agent, but it causes side effects, including genotoxicity with damages the DNA of blood cells. The aim of this work was to evaluate the modulating effect of A, C and E vitamins on genotoxic activity of irinotecan (CPT-11) and to analyse the efficacy of DNA repair in lymphocytes of both patients with diagnosed colorectal carcinoma and healthy individuals in vitro. In healthy donors' cells CPT-11 did not exert a strong, genotoxic effect, both in the presence of vitamins and without them. In turn, a statistically significant increase of DNA migration in the comet tails was noted in patients' lymphocytes. The presence of vitamins A, C and E in incubation solutions acted synergistically, increasing the level of DNA lesions in cells caused by the exposure of the material on tested irinotecan concentrations. Analysis of the efficacy of DNA repair, performed after 2h of postincubation, showed the decrease of DNA percentage in comet tails in all experimental samples.
Asunto(s)
Ácido Ascórbico/farmacología , Camptotecina/análogos & derivados , Linfocitos/efectos de los fármacos , Vitamina A/farmacología , Vitamina E/farmacología , Adulto , Antineoplásicos Fitogénicos/toxicidad , Camptotecina/toxicidad , Ensayo Cometa , Daño del ADN , Reparación del ADN , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , MutágenosRESUMEN
The phenolics: anthocyanin (ATH), sinapoyl esters and activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (POX), ascorbate peroxidase (APX), glutathione peroxidase (GPX) and glutathione reductase (GR), in red cabbage seedlings subjected to Cu2+ stress were investigated. Cu2+ at low doses (0.5 mM), increased the levels of ATH and sinapoyl derivatives in red cabbage. High Cu2+ concentration (2.5 mM) provoked oxidative stress and enhanced thiobarbituric acid reactive substances (TBARS) content in tissues. A lower level of TBARS was correlated with high ATH content. It seems that synthesis of these isoflavonoids is an effective strategy against reactive oxygen species (ROS). The analysis of the antioxidant enzymes activity suggested that peroxidases were the most active enzymes in red cabbage seedlings exposed to Cu2+ stress. It could results from the fact that phenolic compounds (PhC), which could be also substrates for different peroxidases, were the first line of defence against metal stress.