Scholarlink

<p>The search for novel drugs based on natural products combined with nanosystems has circumvented limitations and barriers in cancer treatment. Citrinin (CIT), a mycotoxin produced by the fungus <i>Penicillium citrinum</i>, has demonstrated cytotoxicity in tumor models and may represent a promising antitumor agent. In this study, we aimed to evaluate the cytotoxic, genotoxic, and mutagenic effects of CIT and a liposomal nanoformulation containing CIT (LP-CIT) in MCF7 breast cancer cells. The selected concentrations were based on preliminary range-finding assays to determine optimal cytotoxicity while maintaining assay reliability. The toxicogenetic evaluations and mechanistic analyses included MTT, trypan blue exclusion, cytokinesis-block micronucleus (CBMN) assays, fluorescence confocal microscopy, and molecular docking studies. CIT and LP-CIT showed cytotoxicity in MCF7 cells, with LP-CIT presenting significantly reduced IC50 values (0.90&#xa0;µg/mL) compared to free CIT (18.25&#xa0;µg/mL), possibly due to enhanced cellular uptake via liposomal delivery. Confocal microscopy revealed that both treatments significantly reduced cell viability and increased apoptosis. In addition, CBMN assays demonstrated equivalent cytostatic and mutagenic effects for CIT and LP-CIT. Docking analysis suggested interactions of CIT with mitogen-activated protein kinases, including MAPK-1, B-Raf, and ERK, indicating possible activation of apoptotic pathways via ERK1/2. In conclusion, CIT and its liposomal nanoformulation (LP-CIT) exhibited cytotoxic and mutagenic activity in human breast tumor cells by inducing apoptosis and modulating oncogenic pathways.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Molecular docking and antitumor evaluation of liposomal nanoformulations containing citrinin

  • 期刊论文

  • 发表日期：

    2025年5月1日

查看全文
  • Ag-Anne Pereira Melo de Menezes,
  • Michely Laiany Vieira Moura,
  • José Williams Gomes de Oliveira Filho,
  • Maria Luisa Lima Barreto do Nascimento,
  • Juan Carlos Ramos Gonçalves,
  • Marianna Vieira Sobral,
  • Karinne Kelly Gadelha Marques,
  • Felipe Cavalcanti Carneiro da Silva,
  • Guilherme Barroso L. De Freitas,
  • Vladimir Costa Silva,
  • Shamya Gabriella Corrêa Coêlho,
  • Marjorie Pereira Gualter,
  • Helber Alves Negreiros,
  • João Pedro Alves Damaceno do Lago,
  • Igor Gabriel Barbosa de Sousa,
  • Hercília Maria Lins Rolim,
  • João Marcelo de Castro e Sousa

摘要

The search for novel drugs based on natural products combined with nanosystems has circumvented limitations and barriers in cancer treatment. Citrinin (CIT), a mycotoxin produced by the fungus Penicillium citrinum, has demonstrated cytotoxicity in tumor models and may represent a promising antitumor agent. In this study, we aimed to evaluate the cytotoxic, genotoxic, and mutagenic effects of CIT and a liposomal nanoformulation containing CIT (LP-CIT) in MCF7 breast cancer cells. The selected concentrations were based on preliminary range-finding assays to determine optimal cytotoxicity while maintaining assay reliability. The toxicogenetic evaluations and mechanistic analyses included MTT, trypan blue exclusion, cytokinesis-block micronucleus (CBMN) assays, fluorescence confocal microscopy, and molecular docking studies. CIT and LP-CIT showed cytotoxicity in MCF7 cells, with LP-CIT presenting significantly reduced IC50 values (0.90 µg/mL) compared to free CIT (18.25 µg/mL), possibly due to enhanced cellular uptake via liposomal delivery. Confocal microscopy revealed that both treatments significantly reduced cell viability and increased apoptosis. In addition, CBMN assays demonstrated equivalent cytostatic and mutagenic effects for CIT and LP-CIT. Docking analysis suggested interactions of CIT with mitogen-activated protein kinases, including MAPK-1, B-Raf, and ERK, indicating possible activation of apoptotic pathways via ERK1/2. In conclusion, CIT and its liposomal nanoformulation (LP-CIT) exhibited cytotoxic and mutagenic activity in human breast tumor cells by inducing apoptosis and modulating oncogenic pathways.