Enhancing cisplatin efficacy in hepatocellular carcinoma with selenocystine: The suppression of DNA repair and inhibition of proliferation in hepatoma cells

Pei Yi Wu, Ulfah Hasanah, Sheng Hua Yang, Sin Yi Chen, Yueh Hsia Luo, Chien Chin Chen, Ssu Ching Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Cisplatin (cDDP) is a crucial chemotherapy drug for treating various cancers, including hepatocellular carcinoma (HCC). However, its effectiveness is often hindered by side effects and drug resistance. Selenocystine (SeC) demonstrates potential as an anticancer agent, particularly by inhibiting DNA repair mechanisms. This study explored the synergistic potential of SeC combined with cDDP for treating HCC. Our results show that SeC pretreatment followed by cDDP significantly suppresses HCC cell proliferation more effectively than either treatment alone, with minimal toxicity to normal liver cells. The combination induces significant DNA damage by inhibiting homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Xenograft experiments confirmed that the combined therapy strongly inhibits tumor growth. SeC boost the effectiveness of cDDP by amplifying DNA damage and inhibiting DNA repair, presenting a promising approach to enhancing liver cancer treatment.

Original languageEnglish
Article number111291
JournalChemico-Biological Interactions
Volume405
DOIs
StatePublished - 5 Jan 2025

Keywords

  • Cisplatin
  • DNA damage
  • DNA repair activity
  • Hepatocellular carcinoma
  • Selenocystine

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