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

Abstract

BackgroundGambogic 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. Material and MethodsThe 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, immuno uorescence staining was applied to assess 8-oxo-dG and LC3β levels in SNU-16 cells. ResultsIt was observed that gambogic acid exerted a dose-dependent and statistically signi cant antiproliferative effect on SNU-16 cells. The IC 50 value of gambogic acid in SNU-16 cells was found to be 655.1 nM for 24 hours. Subsequent investigations conducted using the IC 50 dose revealed a signi cant 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. ConclusionThe 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.

Nanostructured lipid carriers loaded with morellic acid for enhanced anticancer efficacy: preparation, characterization, pharmacokinetics and anticancer evaluation

“…GA demonstrated the ability to induce apoptosis in esophageal squamous cell carcinoma cells in a dose-dependent manner, which was achieved by reducing Bcl-2 levels and increasing the levels of Bax, cleaved-PARP1 and cleaved caspase 3/9 [44]. In a study involving gastric signet ring cell carcinoma, GA revealed an upregulation of cleaved caspase 3, Bax, and cleaved PARP, along with a downregulation of Bcl-2 [45]. GA-loaded NLCs have also been reported to inhibit tumor and metastasis growth, potentially due to alterations in MMP-9, BCL-2, and E-cadherin levels [46], and GA has been found to influence the expression of Bax, caspase 3, and caspase 9 in human osteosarcoma [47].…”

Emerging tendencies for the nano-delivery of gambogic acid: a promising approach in oncotherapy

“…Thus, the capacity of GA to promote apoptosis and autophagy is thought to be the cause of its antiproliferative action against cancer cells. 33 …”