2. Academic Validation
  3. Proline metabolism supports the hepatocellular carcinoma cell survival by mitigating ROS generation under nutrient starvation

Proline metabolism supports the hepatocellular carcinoma cell survival by mitigating ROS generation under nutrient starvation

  • Biochem Biophys Res Commun. 2026 Mar 19:805:153392. doi: 10.1016/j.bbrc.2026.153392.
Jinglian Mo 1,  Ziming Liu 2,  Jialin Fu 3,  Qichao Ge 2,  Yiying Qu 4,  Nan Ge 2,  Yang Liu 5
Affiliations

Affiliations

  • 1 Department of Pharmacy, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Hainan Province, China. Electronic address: [email protected].
  • 2 Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
  • 3 Innovative Research Center for Integrated Cancer Omics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
  • 4 Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China; Innovative Research Center for Integrated Cancer Omics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
  • 5 Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China; Innovative Research Center for Integrated Cancer Omics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China. Electronic address: [email protected].
PMID: 41650851 DOI: 10.1016/j.bbrc.2026.153392
Abstract

Background: Proline supplementation promotes proliferation and invasion in cancers under acute nutrient deprivation. However, its molecular basis in hepatocellular carcinoma is not fully understood yet. This study investigates how proline metabolism promotes hepatocellular carcinoma (HCC) cell proliferation and survival during nutrient starvation.

Methods: Proline metabolism-related protein expression in HCC versus paracarcinoma tissues was analyzed using The Cancer Genome Atlas database. HCC cell viability was quantified via Cell Counting Kit 8 assays, and colony formation capacity was evaluated. Intracellular ROS levels were measured by flow cytometry. Autophagic flux was assessed by GFP/mCherry fluorescence ratio and autophagy-related proteins by immunoblotting. Lipid droplet deposition was visualized using Hoechst 33342 and BODIPY 493/503 staining.

Results: Proline metabolism-related proteins were significantly upregulated in HCC tissues compared to paracarcinoma controls. Under acute nutrient stress, exogenous proline reduced cellular ROS levels, attenuated lipid droplet accumulation, and suppressed excessive Autophagy in HCC cells. Proline rescued nutrient deprivation-induced tumor growth inhibition, which could be reversed by H2O2 and rapamycin.

Conclusion: Proline metabolism sustains HCC cell survival during nutrient restriction by reducing ROS accumulation, thereby inhibiting lipid droplet formation and Autophagy.

Keywords

Autophagy; Hepatocellular carcinoma; Oxidative stress; Proliferation; Proline.

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