Molecular mechanism of palmitic acid and its derivatives in tumor progression

Abstract

Palmitic acid (PA) is a saturated fatty acid commonly found in coconut oil and palm oil. It serves as an energy source for the body and plays a role in the structure and function of cell membranes. Beyond its industrial applications, PA has gained attention for its potential therapeutic properties. Modern pharmacological studies have demonstrated that PA exhibits anti-inflammatory, antioxidant, and immune-enhancing effects. In recent years, PA has emerged as a promising anti-tumor agent with demonstrated efficacy against various malignancies including gastric cancer, liver cancer, cervical cancer, breast cancer, and colorectal cancer. Its anti-tumor effects encompass inducing apoptosis in tumor cells, inhibiting tumor cell proliferation, suppressing metastasis and invasion, enhancing sensitivity to chemotherapy, and improving immune function. The main anticancer mechanism of palmitic acid (PA) involves the induction of cell apoptosis through the mitochondrial pathway, facilitated by the promotion of intracellular reactive oxygen species (ROS) generation. PA also exhibits interference with the cancer cell cycle, leading to cell cycle arrest predominantly in the G1 phase. Moreover, PA induces programmed cell autophagy death, inhibits cell migration, invasion, and angiogenesis, and synergistically enhances the efficacy of chemotherapy drugs while reducing adverse reactions. PA acts on various intracellular and extracellular targets, modulating tumor cell signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), endoplasmic reticulum (ER), B Cell Lymphoma-2 (Bcl-2), P53, and other signaling pathways. Furthermore, derivatives of PA play a significant regulatory role in tumor resistance processes. This paper provides a comprehensive review of recent studies investigating the anti-tumor effects of PA. It summarizes the underlying mechanisms through which PA exerts its anti-tumor effects, aiming to inspire new perspectives for the treatment of malignant tumors in clinical settings and the development of novel anti-cancer drugs.

Tetrastigma hemsleyanum (Sanyeqing) root extracts evoke S phase arrest while inhibiting the migration and invasion of human pancreatic cancer PANC-1 cells

“…Fatty acids [ 35 – 37 ] including linoleic acid (14.37%) and 9,12,15-all-cis-Octadecatrienoic acid (9.46%) have shown activity in cancer prevention and treatment. In recent years, a number of studies have shown that palmitic acid has become a promising antineoplastic agent with demonstrated effects on various malignancies including stomach cancer, liver cancer, cervical cancer, breast cancer and colorectal cancer [ 38 – 43 ]. The anti-tumor effects include inducing apoptosis of tumor cells, inhibiting proliferation of tumor cells, inhibiting metastasis and invasion, increasing sensitivity to chemotherapy, and improving immune function.…”

Plasma free fatty acid levels in cervical cancer: concurrent chemoradiotherapy improves abnormal profile

“…Palmitic acid, one of the most common saturated fatty acids, which is both obtained through food and synthesized in the body, accounts for approximately 20%–30% of total fatty acids ( Carta et al, 2017 ). It has been shown that palmitic acid has a particular antitumor effect in malignant tumors such as CC, hepatocellular carcinoma, and intestinal cancer and has achieved a certain degree of therapeutic efficacy ( Wang et al, 2023a ). In recent years, the regulation of autophagy has received much attention in relation to cancer development and treatment ( Yamazaki et al, 2021 ), Ulva intestinalis and Ulva lactuca have been shown to induce autophagic cell death in SiHa cells by up-regulating the expression of Bax and p53 and downregulating the expression of Bcl2, and they also reduced the expression of the viral oncogene HPV-E6 by 1.8 to 2-fold.…”

“…In recent years, the regulation of autophagy has received much attention in relation to cancer development and treatment ( Yamazaki et al, 2021 ), Ulva intestinalis and Ulva lactuca have been shown to induce autophagic cell death in SiHa cells by up-regulating the expression of Bax and p53 and downregulating the expression of Bcl2, and they also reduced the expression of the viral oncogene HPV-E6 by 1.8 to 2-fold. Both algae were characterized and analyzed by GC-MS, and the main active component of both was palmitic acid ( Pal et al, 2021 ; Wang et al, 2023a ). However, Gu et al found that berberine can cause substantial antiproliferative effects on the cervical cancer cell line HeLa by inhibiting intracellular fatty acid synthesis through the activation of AMPK, thereby decreasing the activity of acetyl coenzyme a carboxylase, and exogenous supplementation with palmitic acid rescued this inhibitory effect ( Gu et al, 2020 ).…”

Association between dietary intake of saturated fatty acid subgroups and breast cancer risk

“…14,25,34 A recent study suggested that palmitic acid (C16:0), commonly found in coconut oil and palm oil, exerts anti-tumour effects through inducing apoptosis in tumour cells and so on. 35 Meanwhile, previous research stated that palmitic acid (C16:0) inhibits the autophagy flux in hypothalamic neurons, increasing the risk of developing breast cancer. 36 No prior research has delved into the associations between very long-chain SFAs and breast cancer risk, despite recent findings of negative associations of very long-chain SFAs with other types of cancers, such as colorectal cancer, 37 pancreatic cancer, 38 and prostate cancer.…”