Antitumor effect of dimethyl itaconate on thymic carcinoma by targeting LDHA-mTOR axis

• Published in: Life sciences (1973) Vol. 282; p. 119847
• Main Authors: Hayashi, Keitaro, Nakazato, Yoshimasa, Ouchi, Motoshi, Fujita, Tomoe, Endou, Hitoshi, Chida, Masayuki
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.10.2021; Elsevier BV
• Subjects: Amino acids; Anticancer properties; Antitumor activity; Apoptosis; Cancer; Cell viability; Dimethyl itaconate; Dimethylitaconate; Immunohistochemistry; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; LAT1; LDHA; mTOR; Rapamycin; Thymic carcinoma; Thymus; TOR protein; Western blotting; LAT1; LDHA; Dimethyl itaconate; DI; Thymic carcinoma; mTOR; S6K
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119847

Thymic carcinoma is a rare type of cancer without an established standard pharmaceutical treatment. This study investigated the antitumor effect of dimethyl itaconate (DI), a cell-permeable derivative of itaconate, on human thymic carcinoma cell line. Human thymic carcinoma cell line Ty82 was used to evaluate the effect of DI on cell viability. Western blotting and immunohistochemistry were performed to determine the molecular mechanism of antitumor effects of DI on Ty82. DI suppressed cell growth and promoted apoptosis of Ty82. The suppressive effect of DI on Ty82 was mediated by the downregulation of lactate dehydrogenase A (LDHA), and the subsequent decrease in the activity of mechanistic target of rapamycin (mTOR). DI exhibited synergistic antitumor effects with a specific inhibitor of large neutral amino acid transporter 1 (LAT1), an amino acid transporter currently being investigated as a novel target for cancer therapy. Our findings demonstrate that DI is a novel potential strategy for thymic carcinoma treatment.