Mechanism of anticancer effect of gambogic acid on gastric signet ring cell carcinoma


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Joha Z., Öztürk A., Yulak F., Karataş Ö., Ataseven H.

Medical Oncology, cilt.40, sa.9, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 40 Sayı: 9
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1007/s12032-023-02149-9
  • Dergi Adı: Medical Oncology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, MEDLINE
  • Anahtar Kelimeler: Anticancer, Apoptosis, Autophagy, Gambogic acid
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

Gambogic acid has demonstrated inhibitory effects on the growth of various cancer cell types, such as breast cancer, pancreatic cancer, prostate cancer, lung cancer, and osteosarcoma. This study aims to investigate the antiproliferative activity of Gambogic acid on SNU-16 cells derived from gastric signet ring cell carcinoma and elucidate the underlying mechanisms. The cytotoxic effect of gambogic acid was evaluated in SNU-16 cells by treating them with different concentrations of the compound, and the XTT cell viability assay was employed to assess cell viability. ELISA was used to measure bax, BCL-2, caspase 3, PARP, and 8-oxo-dG levels. Additionally, immunofluorescence staining was applied to assess 8-oxo-dG and LC3β levels in SNU-16 cells. It was observed that gambogic acid exerted a dose-dependent and statistically significant antiproliferative effect on SNU-16 cells. The IC50 value of gambogic acid in SNU-16 cells was found to be 655.1 nM for 24 h. Subsequent investigations conducted using the IC50 dose revealed a significant upregulation of apoptotic proteins including cleaved caspase 3, Bax, and cleaved PARP (p < 0.001), along with a downregulation of BCL-2 (p < 0.001), an anti-apoptotic protein. Moreover, the administration of this drug led to an upregulation of 8-oxo-dG (p < 0.001), a widely acknowledged biomarker indicating oxidative damage in DNA, as well as an increase in LC3β levels (p < 0.05), a marker associated with autophagy. The antiproliferative effect of gambogic acid against gastric signet ring cell carcinoma is attributed to its ability to induce apoptosis and autophagy. This discovery highlights the promising potential of gambogic acid as a treatment option for gastric signet ring cell carcinoma.