XSJ151 is a topoisomerase I inhibitor that stabilizes the DNA-topoisomerase I covalent complex, inducing DNA double-strand breaks. The DNA damage caused by XSJ151 activates the p53-p21 signaling pathway, specifically regulating the expression of cyclins, resulting in G2/M phase cell cycle arrest. Additionally, it disrupts the dynamic equilibrium of Bcl-2 family proteins, thereby triggering apoptosis in gastric cancer cells. XSJ151 is applicable for research in gastric cancer.

XSJ151 exhibits significant cytotoxicity against several gastric cancer cell lines, including AGS (IC₅₀ = 0.088 μM), MGC803 (IC₅₀ = 0.592 μM), HGC27 (IC₅₀ = 1.951 μM), and SGC7901 (IC₅₀ = 11.121 μM), while showing lower toxicity to normal cell lines such as GES-1 (IC₅₀ = 0.202 μM) and HIEC (IC₅₀ > 40 μM). It inhibits colony formation in gastric cancer cells in a concentration-dependent manner at 0.1-2.5 nM over 7-10 days, reducing AGS colonies from 74 to 22 and MGC803 colonies from 68 to 21 at 2.5 nM. At 2.5-10 nM for 24 hours, XSJ151 induces G2/M phase arrest in AGS and MGC803 cells, significantly enriching G2/M phase cell populations. It also upregulates G2/M phase-associated proteins (p53, p21, CCNB) and S phase marker CCNA while downregulating G1 phase-specific protein CCNE at 44-600 nM for 48 hours. XSJ151 at 88-600 nM (48 hours) induces apoptosis in AGS and MGC803 cells by upregulating BAD and BAX proteins and downregulating Bcl-2. It increases the number of γ-H2AX foci in the nuclei of these cells, indicating DNA double-strand breaks, and elevates γ-H2AX protein levels significantly. Furthermore, XSJ151 effectively inhibits topoisomerase I-mediated DNA relaxation at 150-200 μM for 30 minutes and downregulates topoisomerase I protein expression at 44-600 μM over 48 hours.