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<p>Developing targeted therapeutic drugs for liver cancer remains a significant scientific and clinical challenge. Previous research by the authors showed that taraxasterol (TS) can enhance the antitumor immune response of T-lymphocytes, inhibiting the growth of liver cancer cells both in vivo and in vitro. To improve the targeting ability and efficacy of TS, the authors synthesized a novel compound, Bio-SS-TS, which utilizes the high expression of biotin receptors on tumor cell membranes to link biotin to TS for increased targeting to hepatocellular carcinoma cells, and its disulfide bond can be specifically hydrolyzed by high - level glutathione (GSH) in tumor cells to release the active component TS. In vitro, Bio-SS-TS reduced liver cancer cell (HepG2 and Huh7) proliferation, impaired mitochondrial membrane potential, decreased intracellular GSH content in tumor cells, increased the reactive oxygen species level, and promoted the release of cytochrome c. Endogenous GSH in cancer cells reduced the disulfide bond in Bio-SS-TS, releasing active TS components. In vivo, treatment with Bio-SS-TS caused no significant change in mouse body weight and no toxicity to the main organs. The present study comprehensively demonstrates that Bio-SS-TS exerts a potent anti - liver cancer effect by enhancing mitochondria-dependent apoptosis, which may provide a new candidate for targeted liver cancer therapy.</p>

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Bio-SS-TS as a Targeted Antitumor Drug Exerts an Anti-Liver Cancer Effect by Enhancing Mitochondria-Dependent Apoptosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月28日

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  • Jian Li,
  • Yuanhua Qin,
  • Mengjuan Li,
  • Jingli Shang,
  • Hang Chen,
  • Yadi Liu,
  • Bingjie Liu,
  • Pingxin Zhou,
  • Tiesuo Zhao,
  • Ge Wang,
  • Chunpo Ge,
  • Yu Zhang,
  • Huijie Jia,
  • Feng Ren

摘要

Developing targeted therapeutic drugs for liver cancer remains a significant scientific and clinical challenge. Previous research by the authors showed that taraxasterol (TS) can enhance the antitumor immune response of T-lymphocytes, inhibiting the growth of liver cancer cells both in vivo and in vitro. To improve the targeting ability and efficacy of TS, the authors synthesized a novel compound, Bio-SS-TS, which utilizes the high expression of biotin receptors on tumor cell membranes to link biotin to TS for increased targeting to hepatocellular carcinoma cells, and its disulfide bond can be specifically hydrolyzed by high - level glutathione (GSH) in tumor cells to release the active component TS. In vitro, Bio-SS-TS reduced liver cancer cell (HepG2 and Huh7) proliferation, impaired mitochondrial membrane potential, decreased intracellular GSH content in tumor cells, increased the reactive oxygen species level, and promoted the release of cytochrome c. Endogenous GSH in cancer cells reduced the disulfide bond in Bio-SS-TS, releasing active TS components. In vivo, treatment with Bio-SS-TS caused no significant change in mouse body weight and no toxicity to the main organs. The present study comprehensively demonstrates that Bio-SS-TS exerts a potent anti - liver cancer effect by enhancing mitochondria-dependent apoptosis, which may provide a new candidate for targeted liver cancer therapy.