2. Academic Validation
  3. Real-time profiling of brazilin-induced cytotoxic responses in HepG2 cells and exosome-associated metabolic signaling under lipid accumulation

Real-time profiling of brazilin-induced cytotoxic responses in HepG2 cells and exosome-associated metabolic signaling under lipid accumulation

  • Tissue Cell. 2026 May 22:102:103626. doi: 10.1016/j.tice.2026.103626.
Seongje Hong 1,  Yeon Jin Lim 2,  Do Su Lim 3,  Tae Woo Jung 3,  Dokyoung Kim 4,  Kyung Oh Jung 5
Affiliations

Affiliations

  • 1 Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea.
  • 2 Department of Precision Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
  • 3 Department of Pharmacology, College of Medicine, Graduate School of, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea.
  • 4 Department of Precision Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Core Research Institute (CRI), Kyung Hee University, Seoul 02447, Republic of Korea; Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Center for Converging Humanities, Kyung Hee University, Seoul 02447, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea; UC San Diego Materials Research Science and Engineering Center, La Jolla, CA 92093, USA. Electronic address: [email protected].
  • 5 Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea. Electronic address: [email protected].
PMID: 42184491 DOI: 10.1016/j.tice.2026.103626
Abstract

Hepatocellular carcinoma (HCC) frequently arises in metabolically altered livers and often exhibits limited responses to systemic therapies, highlighting the need for agents that target both tumor cell survival and metabolic vulnerabilities. Brazilin, a bioactive compound from Caesalpinia sappan, has been reported to exert Anticancer activities, yet its effects on intercellular communication under lipid-enriched conditions remain unclear. Here, we profiled brazilin-induced cytotoxic responses in HepG2 cells using real-time imaging-based monitoring of cell morphology, number, and area, together with viability assays. Brazilin reduced HepG2 viability in a concentration-dependent manner and suppressed pro-survival signaling (Akt phosphorylation and Bcl-2), accompanied by Caspase-3 cleavage and increased Annexin V positivity, indicating apoptosis-associated cytotoxicity. We then isolated extracellular vesicles released from brazilin-treated HepG2 cells and confirmed exosome-like characteristics by TEM, exosomal marker expression (CD9/CD63/CD81), and nanoparticle tracking analysis. Notably, in palmitate/oleate-loaded HepG2 cells, exosomes derived from brazilin-treated cells modulated metabolic and stress-associated proteins, including reduced CPT1A and SOD1 levels and increased p27 expression, consistent with altered fatty-acid oxidation-related signaling under lipid accumulation. Collectively, these findings suggest that brazilin exerts direct cytotoxic effects in HepG2 cells and that exosomes released upon brazilin exposure may contribute to metabolic signaling changes in lipid-loaded Cancer cells.

Keywords

Brazilin; Cytotoxicity; Exosomes; Hepatocellular carcinoma; Lipid accumulation.

Figures
Products