Pentadecanoic Acid (C15:0) at Naturally Occurring Circulating Concentrations Has Selective Anticancer Activities...

Area of Science:

• Nutritional biochemistry
• Cancer biology
• Pharmacology

Background:

• Pentadecanoic acid (C15:0), found in whole dairy fat, exhibits anticancer properties at high doses.
• Its efficacy at naturally occurring circulating concentrations remains less understood.

Purpose of the Study:

• To investigate the dose-dependent antiproliferation activities of C15:0 against human cancer cell lines.
• To compare oncogenic alterations in cell lines responsive versus non-responsive to C15:0.

Main Methods:

• The Eurofins OncoPanel™ Cell Proliferation Assay was used to screen C15:0.
• Ten concentrations of C15:0 (1.5 nM to 50 µM) were tested against 94 human cancer cell lines.
• Oncogenic alterations were analyzed using DepMap data.

Main Results:

• C15:0 demonstrated dose-dependent antiproliferation in 13.8% of cell lines (EC50 ≤ 50 µM), predominantly non-Hodgkin B-cell lymphomas.
• Robust activity was observed in four cell lines, all non-Hodgkin B-cell lymphomas.
• C15:0-responsive cell lines showed a significant association with CCND3 mutations (22% vs. 1.6%, p=0.007).

Conclusions:

• C15:0 possesses selective, dose-dependent anticancer activity at naturally occurring concentrations.
• C15:0's potential against cancers with CCND3 alterations warrants further investigation.
• Understanding C15:0 deficiency and CCND3 alterations may be crucial for certain cancer types, especially in young adults.