Microbiota-gut-brain axis and the central nervous system Microbiota-gut-brain axis and the central nervous system

Luteolin is a flavonoid, which has been extensively investigated due to its antitumor effects; however, the underlying mechanisms of its action remain largely unknown. The present study aimed to investigate the role of luteolin in breast cancer (BC), and explored how luteolin suppresses the growth and induces the apoptosis of BC cells. The MTS assay was used to determine the anticancer activity of luteolin. Colony formation and Transwell assays were performed to evaluate the effects of luteolin on cell growth and invasion. Cell cycle progression and apoptosis were analyzed by flow cytometry. In addition, western blotting was performed to analyze cellular apoptosis and signaling pathways elicited by luteolin. The present study revealed that the proliferation of the BC cell line MDA‑MB‑231 was effectively suppressed by luteolin in a dose‑dependent manner. Additionally, luteolin was revealed to increase apoptotic rates in BC cells. Dose‑dependent cell cycle arrest in S phase was observed following treatment with luteolin in MDA‑MB‑231 cells. Mechanistically, luteolin reduced telomerase levels in a dose‑dependent manner. Additionally, luteolin inhibited phosphorylation of the nuclear factor‑κB inhibitor α and its target gene c‑Myc, to suppress human telomerase reverse transcriptase (hTERT) expression, which encodes the catalytic subunit of telomerase. Collectively, the results of the present study indicated that luteolin may inhibit BC cell growth by targeting hTERT, suggesting that the mechanism of hTERT regulation by luteolin may justify further study regarding its potential as a therapeutic target for BC treatment.

Cancer immunotherapy is exploited for the treatment of disease by modulating the immune system. Since the conventional in vivo animal and 2D in vitro models insufficiently recapitulate the complex tumor immune microenvironment (TIME) of the original tumor. In addition, due to the involvement of the immune system in cancer immunotherapy, more physiomimetic cancer models, such as patient-derived organoids (PDOs), are required to evaluate the efficacy of immunotherapy agents. On the other hand, the dynamic interactions between the neoplastic cells and non-neoplastic host components in the TIME can promote carcinogenesis, tumor metastasis, cancer progression, and drug resistance of cancer cells. Indeed, tumor organoid models can properly recapitulate the TIME by preserving endogenous stromal components including various immune cells, or by adding exogenous immune cells, cancer-associated fibroblasts (CAFs), vasculature, and other components. Therefore, organoid culture platforms could model immunotherapy responses and facilitate the immunotherapy preclinical testing. Here, we discuss the various organoid culture approaches for the modeling of TIME and the applications of complex tumor organoids in testing cancer immunotherapeutics and personalized cancer immunotherapy.

Branched-chain amino acids (BCAAs), including valine, leucine, and isoleucine, are crucial amino acids with significant implications in tumorigenesis across various human malignancies. Studies have demonstrated that altered BCAA metabolism can influence tumor growth and progression. Increased levels of BCAAs have been associated with tumor growth inhibition, indicating their potential as anti-cancer agents. Conversely, a deficiency in BCAAs can promote tumor metastasis to different organs due to the disruptive effects of high BCAA concentrations on tumor cell migration and invasion. This disruption is associated with tumor cell adhesion, angiogenesis, metastasis, and invasion. Furthermore, BCAAs serve as nitrogen donors, contributing to synthesizing macromolecules such as proteins and nucleotides crucial for cancer cell growth. Consequently, BCAAs exhibit a dual role in cancer, and their effects on tumor growth or inhibition are contingent upon various conditions and concentrations. This review discusses these contrasting findings, providing valuable insights into BCAA-related therapeutic interventions and ultimately contributing to a better understanding of their potential role in cancer treatment.

Tumor organoid models have emerged as valuable 3D in vitro systems to study cancer behavior in a physiologically relevant environment. The composition and architecture of the extracellular matrix (ECM) play critical roles in tumor organoid culture by influencing the tumor microenvironment and tumor behavior. Traditional matrices such as Matrigel and collagen, have been widely used, but their batch-to-batch variability and limited tunability hinder their reproducibility and broader applications. To address these challenges, researchers have turned to synthetic/engineered matrices and biopolymer-based matrices, which offer precise tunability, reproducibility, and chemically defined compositions. However, these matrices also present challenges of their own. In this review, we explore the significance of ECMs in tumor organoid culture, discuss the limitations of commonly used matrices, and highlight recent advancements in engineered/synthetic matrices for improved tumor organoid modeling.