Targeting lipid metabolism with natural products: A novel strategy for gastrointestinal cancer therapy

Abstract

Gastrointestinal cancer (GIC), including gastric cancer and colorectal cancer, is a common malignant tumor originating from gastrointestinal epithelial cells. Although the pathogenesis of GIC remains unclear, aberrant lipid metabolism has emerged as a hallmark of cancer. Several enzymes, proteins, and transcription factors are involved in lipid metabolism reprogramming in GIC, and their abnormal expression can promote lipid synthesis and accumulation of lipid droplets through numerous mechanisms, thereby affecting the growth, proliferation, and metastasis of GIC cells.Studies show that some natural compounds, including flavonoids, alkaloids, and saponins, can inhibit the de novo synthesis of lipids in GIC, reduce the level of lipid accumulation, and subsequently, inhibit the occurrence and development of GIC by regulating Sterol regulatory element-binding protein 1 (SREBP-1), adenosine monophosphate-activated protein kinase (AMPK), 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR), phosphatidylinositol-3-kinase/Akt and the mammalian target of rapamycin PI3K/Akt/mTOR, amongst other targets and pathways. Therefore, targeting tumor lipid metabolism is the focus of anti-gastrointestinal tumor therapy. Although most natural products require further high-quality studies to firmly establish their clinical efficacy, we review the potential of natural products in the treatment of GIC and summarize the application prospect of lipid metabolism as a new target for the treatment of GIC, hoping to provide a reference for drug development for gastrointestinal tumors.

Discovery of a novel lipid metabolism-related gene signature to predict outcomes and the tumor immune microenvironment in gastric cancer by integrated analysis of single-cell and bulk RNA sequencing

“…Through inflammatory reactions, abnormalities in lipid metabolism may contribute to the growth of stomach cancer. Abnormal lipid metabolism can activate inflammatory cells and release inflammatory factors, thereby exerting an influence on the development of GC [ 25 , 43 ]. Recent studies have employed LMRGs to create novel predictive models for a variety of tumor types, including papillary thyroid cancer, colon adenocarcinoma, and bladder cancer.…”

“…Specific lipid molecules, including phosphatidylinositol, fatty acids, and cholesterol metabolites, also regulate signaling pathways linked to tumor growth, invasion, and metastasis. Furthermore, the involvement of lipid metabolism in drug resistance poses a significant challenge in treating GC [ 23 – 25 ]. It was reported that reprogrammed lipid metabolism allows GC cells to use lipids as an energy source, supporting their rapid growth and division.…”

Natural products targeting the MAPK-signaling pathway in cancer: overview

“…Alkaloids are a class of basic nitrogen-containing organic compounds found in nature, most of which have complex circular structures. Alkaloids are one of the clinically effective ingredients in the treatment of diseases (Gjorgieva Ackova et al 2023 ; Guo et al 2023 ). Wang et al ( 2018a , b , c , d ) found that evodiamine could upregulate the phosphorylation levels of p38 and JNK in glioblastoma multiforme cells, which led cancer cell apoptosis.…”

Gypenoside Inhibits Gastric Cancer Proliferation by Suppressing Glycolysis via the Hippo Pathway

“…In recent years, accumulated studies have explored the potential of targeting metabolism to in uence cancer progression 9 . Natural products are gaining recognition as a therapeutic modality to modulate metabolic reprogramming and serve as convenient natural remedies 10,11 . Some natural products have been proven to exhibit superior inhibitory effects on cancer progression and have shown promise in mitigating toxic side effects induced by radiotherapy, chemotherapy, or targeted therapies 12 .…”