2. Academic Validation
  3. Vitamin C enhances the sensitivity of osteosarcoma to arsenic trioxide via inhibiting aerobic glycolysis

Vitamin C enhances the sensitivity of osteosarcoma to arsenic trioxide via inhibiting aerobic glycolysis

  • Toxicol Appl Pharmacol. 2023 Dec 30:482:116798. doi: 10.1016/j.taap.2023.116798.
Ying Liu 1,  Jinrui Yue 2,  Zijing Ren 1,  Mingyu He 1,  Ao Wang 2,  Jiajie Xie 2,  Tao Li 1,  Guoxin Liu 1,  Xuting He 2,  Shiyu Ge 1,  Ye Yuan 3,  Lei Yang 4
Affiliations

Affiliations

  • 1 Department of Pharmacology (The State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.
  • 2 Department of Pharmacy (The University Key Laboratory of Drug Research, Heilongjiang Province), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China.
  • 3 Department of Pharmacy (The University Key Laboratory of Drug Research, Heilongjiang Province), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China; National key laboratory of frigid cardiovascular disease, Harbin, China. Electronic address: [email protected].
  • 4 Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Laboratory of Hepatosplenic Surgery of Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China; NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
PMID: 38160894 DOI: 10.1016/j.taap.2023.116798
Abstract

Osteosarcoma (OS) is a common malignant tumor disease in the department of orthopedics, which is prone to the age of adolescents and children under 20 years old. Arsenic trioxide (ATO), an ancient poison, has been reported to play a critical role in a variety of tumor treatments, including OS. However, due to certain poisonous side effects such as cardiotoxicity and hepatotoxicity, clinical application of ATO has been greatly limited. Here we report that low doses of ATO (1 μM) observably reduced the half-effective inhibitory concentration (IC50) of vitamin C on OS cells. Compared with the treatment alone, the synthetic application of vitamin C (VitC, 800 μM) and ATO (1 μM) significantly further inhibited the proliferation, migration, and invasion of OS cells and promoted cell Apoptosis in vitro. Meanwhile, we observed that the combined application of VitC and ATO directly suppresses the aerobic glycolysis of OS cells with the decreased production of pyruvate, lactate, and ATP via inhibiting the expression of the critical glycolytic genes (PGK1, PGM1, and LDHA). Moreover, the combination of VitC (200 mg/kg) and ATO (1 mg/kg) with tail vein injection significantly delayed OS growth and migration of nude mice by inhibiting aerobic glycolysis of OS. Thus, our results demonstrate that VitC effectively increases the sensitivity of OS to low concentrations of ATO via inhibiting aerobic glycolysis to alleviate the toxic side effects of high doses of arsenic trioxide, suggesting that synthetic application of VitC and ATO is a promising approach for the clinical treatment of human OS.

Keywords

Aerobic Glycolysis; Arsenic Trioxide; Osteosarcoma; Vitamin C; cancer Treatment.

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