Abstract
Background The detail of mechanism involving in PP-10 anti-cancer activity remains to be elucidated, and the effect on HCC cells is unknown. Methods: MTT and colony formation assays were used to determine the effect of PP-10 on cell growth. Flow cytometry analysis and Hoechst 33258 were used to assess apoptosis. Gene set enrichment analysis (GSEA) was used to explore changes in apoptosis-associated pathways. Western blotting was used to detect protein expression levels. Results: In our study, PP-10 significantly suppressed cancer cell viability while had low toxicity to normal cells, with the HCC cell lines HepG2 and HuH7 being particularly sensitive to PP-10 treatment. PP-10 induced mitochondrial-related apoptosis in HepG2 and HuH7 cells. Moreover, GSEA showed that the MAPK signaling pathway could be correlated with PP-10–induced apoptosis. We used western blotting to confirm that PP-10 induced apoptosis in HepG2 and HuH7 cells by modulating the JNK/SPAK signaling and inhibiting the STAT3 signaling pathway. Conclusion: Collectively, our results show that PP-10 induces apoptosis via the JNK/SPAK and STAT3 signaling pathways in HepG2 and HuH7 hepatocarcinoma cells.
Highlights
Primary liver cancer is the second leading cause of cancerrelated death worldwide and is a major public health challenge
We explored the molecular mechanism of PP-10, a compound isolated from Paris polyphylla var. yunnanensis that inhibits the proliferation of human hepatocellular carcinoma (HCC) cells
The expression levels of c-JUN were increased (Figure 4CDEF). These results show that the JNK/SPAK signaling pathway was activated by PP-10 and induced apoptosis in Hepg2 and HuH7 cells
Summary
Primary liver cancer is the second leading cause of cancerrelated death worldwide and is a major public health challenge. Primary liver cancer includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, and other rare tumors that together account for more than 90% of patients with hepatocellular carcinoma (Sia et al, 2017). Gene set enrichment analysis (GSEA) was used to explore changes in apoptosis-associated pathways. Results: In our study, PP-10 significantly suppressed cancer cell viability while had low toxicity to normal cells, with the HCC cell lines HepG2 and HuH7 being sensitive to PP-10 treatment. PP-10 induced mitochondrial-related apoptosis in HepG2 and HuH7 cells. We used western blotting to confirm that PP-10 induced apoptosis in HepG2 and HuH7 cells by modulating the JNK/SPAK signaling and inhibiting the STAT3 signaling pathway. Conclusion: Collectively, our results show that PP-10 induces apoptosis via the JNK/SPAK and STAT3 signaling pathways in HepG2 and HuH7 hepatocarcinoma cells
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