RESUMO
Breast cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese medicine, Boswellia carterii has been extensively used to treat various cancers, such as BC. However, the anti-BC effect and underlying mechanism of Boswellia carterii remain largely unclear. The aim of this study is to explore the therapeutic effect of Boswellia carterii n-hexane extract (BCHE) against BC as well as its underlying mechanism. The present study showed that BCHE significantly suppressed the viability of human BC cells. Moreover, BCHE exhibited potent anti-BC activity in vivo with no significant toxic effects. Additionally, BCHE induced ferroptosis via increased Transferrin expression and the intracellular accumulation of Fe2+, as well as decreased glutathione peroxidase 4 (GPX4) expression and the upregulation of reactive oxygen species (ROS)-induced lipid peroxidation in BC cells. In vivo experimental results also demonstrated that BCHE effectively induced ferroptosis through GPX4 downregulation and Transferrin upregulation in tumor-bearing mice. Overall, BCHE inhibited the growth of BC cells by inducing ferroptosis mediated by modulating the iron accumulation pathway and the lipid peroxidation pathway. Therefore, BCHE could serve as a potential ferroptosis-targeting drug for treating BC.
Assuntos
Boswellia , Neoplasias da Mama , Ferroptose , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Extratos Vegetais , Transferrina , Ferroptose/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Animais , Transferrina/metabolismo , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Linhagem Celular Tumoral , Boswellia/química , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células/efeitos dos fármacos , Hexanos/química , Regulação para Baixo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos Nus , Camundongos Endogâmicos BALB CRESUMO
The gut microbiota, known as the "forgotten organ" and "human second genome," comprises a complex microecosystem. It significantly influences the development of various tumors, including colorectal, liver, stomach, breast, and lung cancers, through both direct and indirect mechanisms. These mechanisms include the "gut-liver" axis, the "lung-intestine" axis, and interactions with the immune system. The intestinal flora exhibits dual roles in cancer, both promoting and suppressing its progression. Traditional Chinese medicine (TCM) can alter cancer progression by regulating the intestinal flora. It modifies the intestinal flora's composition and structure, along with the levels of endogenous metabolites, thus affecting the intestinal barrier, immune system, and overall body metabolism. These actions contribute to TCM's significant antitumor effects. Moreover, the gut microbiota metabolizes TCM components, enhancing their antitumor properties. Therefore, exploring the interaction between TCM and the intestinal flora offers a novel perspective in understanding TCM's antitumor mechanisms. This paper succinctly reviews the association between gut flora and the development of tumors, including colorectal, liver, gastric, breast, and lung cancers. It further examines current research on the interaction between TCM and intestinal flora, with a focus on its antitumor efficacy. It identifies limitations in existing studies and suggests recommendations, providing insights into antitumor drug research and exploring TCM's antitumor effectiveness. Additionally, this paper aims to guide future research on TCM and the gut microbiota in antitumor studies.