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Blocking L-carnitine synthesis by meldonium prolongs the survival in mice with pancreatic cancer

Year: 2026
Type: article
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is the cancer with poorest prognosis, with metabolic reprogramming reported. We investigated metabolic alterations in mice with PDAC using capillary electrophoresis-mass spectrometry (CE-MS) and mass spectrometry imaging (MSI). o-Acetylcarnitine, a metabolite of carnitine, and acetyl-CoA increased during cancer progression in a PDAC mouse model by CE-MS, while MSI revealed that o-acetylcarnitine was mainly localized in PDAC cells. Also, immunohistochemistry showed overexpression of γ-butyrobetaine 2-oxoglutarate dioxygenase 1 (BBOX1), which synthesizes carnitine from γ-butyrobetaine, mainly in PDAC cells. Meldonium, an inhibitor of BBOX1, inhibited PDAC proliferation and cytokine secretion, thereby prolonging the survival of PDAC-bearing mice, accompanied by improved skeletal muscle atrophy. In patients undergoing PDAC resection, BBOX1 expression was determined as an independent poor prognostic factor for overall survival. Therefore, these results suggest that blocking L-carnitine synthesis would improve the prognosis of patients with PDAC.
Source: iScience
DOI: 10.1016/j.isci.2026.117071
Authors: Makoto Sano, Hideaki Ijichi, Sho Tabata, Akiyoshi Hirayama, Shuichi Shimma, Yohei Masugi, Yoshimi Ichimaru, Jinsuk Kim, Gen Kimura, Koji Miyabayashi, Ryota Takahashi, Hiroto Hatakeyama, Takahiro Suzuki, Atsushi Masamune, Tomoyoshi Soga, Mitsuhiro Fujishiro
Institutions: Nihon University, National Institute of Occupational Safety and Health, The University of Tokyo, Keio University, Keio University Shonan Fujisawa, The University of Osaka, Tokai University, Shonan University of Medical Sciences, Chiba University, Tohoku University
Language: English
Subfield: Cancer Research
Open Access status: gold
Estimated APC paid: $3,240
OpenAlex ID: W7196999300
FWCI:
Cites: 53
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