DOI: 10.32571/ijct.1883946 ISSN: 2602-277X

Comparative Evaluation of Oleanolic Acid and Ursolic Acid Reveals Pathway-Selective Anticancer Effects in SH-SY5Y Neuroblastoma Cells

Ozden Ozgun Acar
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Cancer continues to impose a major global health burden, largely driven by the aberrant regulation of cell growth and survival pathways. This has prompted sustained investigations into bioactive compounds of natural origin. This study presents a comparative evaluation of oleanolic acid (OA) and ursolic acid (UA) in SH-SY5Y neuroblastoma cells using integrated experimental and computational approaches. Cell viability assays revealed concentration-dependent cytotoxic effects for both compounds. Gene expression analyses demonstratedcoordinated modulation of pathways related to apoptosis, cell cycle regulation, oncogenic signaling, and inflammation. OA showed stronger modulation of apoptosis-related and proliferation-associated gene expression patterns, including increased expression of caspase-related transcripts and downregulation of KRAS and C-MYC. In contrast, UA preferentially influenced tumor suppressor and stress-response signaling, with notable increased in p53 and PTEN expression. p53- mediated transcriptional activation was further supported by a luciferase reporter assay in HEK293 cells, which demonstrated higher transcriptional activity following UA treatment compared to OA. Molecular docking and molecular dynamics simulations provided complementary insights, suggesting preferential interactions of OA with KRAS and UA with MDM2. Overall, these findings highlight structure–function relationships underlying pathway-selective anticancer mechanisms of pentacyclic triterpenoids.

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