Lauric acid (LAA) is a 12-carbon medium-chain fatty acid that reportedly has antitumor and muscle-protecting effects. However, the details of these antitumor effects remain unclear. Therefore, in this study, we investigated the mechanism underlying the antitumor effects of LAA in CT26 and HT29 colorectal cancer (CRC) cell lines. Our in vitro findings demonstrated that LAA suppressed CRC cell proliferation, induced mitochondrial oxidative stress (reactive oxygen species (ROS)), inhibited oxidative phosphorylation (OXPHOS), and induced apoptosis. Moreover, in vivo analysis of LAA showed a more pronounced antitumor effect in CT26 cells in a syngeneic mouse tumor model than in vitro; therefore, we further investigated its impact on host antitumor immunity. We observed that LAA increased the number of effector T cells in mouse tumors, while in vitro LAA activated mouse splenocytes (SplC) and promoted OXPHOS. In two-dimensional co-culture of SplC and CT26 cells, LAA induced cell death in cancer cells. In three-dimensional co-culture, LAA promoted SplC infiltration and suppressed the formation of tumor spheres. Thus, LAA may exert antitumor effects through increased ROS production in cancer cells and effector T cell activation via increased energy metabolism. These results suggest that LAA, when used in combination with existing anti-cancer drugs, is likely to exhibit sensitizing effects in terms of both antitumor and antitumor immune effects, and future clinical studies are anticipated.
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http://dx.doi.org/10.3390/ijms26051953 | DOI Listing |
J Cell Sci
March 2025
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Mitochondria perform diverse functions, such as producing ATP through oxidative phosphorylation, synthesizing macromolecule precursors, maintaining redox balance, and many others. Given this diversity of functions, we and others have hypothesized that cells maintain specialized subpopulations of mitochondria. To begin addressing this hypothesis, we developed a new dual-purification system to isolate subpopulations of mitochondria for chemical and biochemical analyses.
View Article and Find Full Text PDFFASEB J
March 2025
Cancer Center, The First Affiliated Hospital of Jilin University, Changchun, Jilin, China.
Breast cancer (BC) is one of the most common malignant tumors among women, accounting for 24.5% of all cancer cases and leading to 15.5% of cancer-related mortality.
View Article and Find Full Text PDFGlycobiology
March 2025
Department of Science and Technology, Seikei University, Tokyo 180-8633, Japan.
Calreticulin (CRT), a chaperone that possesses both lectin and chaperone domains, is localized in the endoplasmic reticulum (ER). CRT has diverse functions and localizations; thus, CRT is a multifunctional protein. Particularly in the ER, CRT mainly aids in the proper folding of nascent glycoproteins as lectin chaperones.
View Article and Find Full Text PDFClin Exp Immunol
March 2025
School of Medicine, Guizhou University, Guiyang 550025, China.
Introduction: Immunotherapy has rapidly become a primary treatment option for many lung cancer patients because of its success in treating this prevalent and deadly disease. However, the success of immunotherapy relies on overcoming the immunosuppressive tumour microenvironment, making remodelling this environment a potential strategy for lung cancer therapy. Research suggests that Toll-like receptor (TLR) agonists can impede tumour growth by promoting the conversion of tumour-associated macrophages into an M1-like state or enhancing dendritic cell development.
View Article and Find Full Text PDFAdv Healthc Mater
March 2025
Department of Ultrasound, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, 361000, P. R. China.
The abnormal tumor mechanical microenvironment due to specific cancer-associated fibroblasts (CAFs) subset and low tumor immunogenicity caused by inefficient conversion of active chemotherapeutic agents are two key obstacles that impede patients with desmoplastic tumors from achieving stable and complete immune responses. Herein, it is demonstrated that FAP-αCAFs-induced stromal stiffness accelerated tumor progression by precluding cytotoxic T lymphocytes. Subsequently, a cascade-responsive nanoprodrug capable of re-educating FAP-αCAFs and amplifying tumor immunogenicity for potentiated cancer mechanoimmunotherapy is ingeniously designed.
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