Polyphyllin VII induces apoptosis and autophagy via mediating H2O2 levels and the JNK pathway in human osteosarcoma U2OS cells

Abstract

Polyphyllin VII, a compound extracted from the rhizomes of Paris polyphylla, has strong antitumor effects on various human tumor cell lines. However, few studies have reported the possible effect of Polyphyllin VII on human osteosarcoma (OS) cell lines. The present study revealed that Polyphyllin VII promoted OS cell apoptosis and inhibited cell proliferation via upregulating the expression of LC3II, Atg5, Atg7 and the Atg12-Atg5 complex. By contrast, treatment of OS cells with Polyphyllin VII downregulated Atg12 and p62 expression. Following treatment with class III PI 3-kinase inhibitor (3-MA; an autophagy inhibitor), the Polyphyllin VII-mediated apoptotic effect was reversed. These findings indicated that the inhibition of autophagy could attenuate U2OS cell apoptosis in cells treated with high concentrations of Polyphyllin VII. The present study also demonstrated that Polyphyllin VII upregulated the intracellular hydrogen peroxide (H 2 O 2) levels in U2OS cells. However, treatment of U2OS cells with N-acetyl-L cysteine (NAC) effectively reversed this effect. The western blot analysis results indicated that the c-Jun N-terminal kinase (JNK) signaling pathway was closely associated with Polyphyllin VII-induced apoptosis and autophagy. In conclusion, the results of the present study demonstrated that Polyphyllin VII could effectively inhibit cell viability and promote autophagy and apoptosis in U2OS cells. In addition, the mechanism underlying these effects could be associated with the intracellular H 2 O 2 levels and the JNK signaling pathway.

Polyphyllin VII induces autophagy‐dependent ferroptosis in human gastric cancer through targeting T‐lymphokine‐activated killer cell‐originated protein kinase

“…Previous studies have reported that PPVII induces a variety of cell death modes, such as apoptosis, autophagy, and programmed necrosis, by activating c‐Jun N‐terminal kinase (JNK) signaling or inhibiting protein kinase B (Akt) signaling in a variety of tumor types (Ahmad, Gamallat, et al, 2021; X. Li et al, 2021; D. Pang et al, 2019; C. Zhang, Jia, Wang, et al, 2016; Zhang, et al, 2015). Both JNK and Akt are downstream kinases of TOPK, activated by TOPK phosphorylation but not limited to the regulation of TOPK (Song et al, 2019; Wu et al, 2019).…”

Polyphyllin VII induces CTC anoikis to inhibit lung cancer metastasis through EGFR pathway regulation

“…Polyphyllin VII, a steroidal saponin derived from Paris polyphylla Sm., possesses potent anticancer activity against various human cancer cell lines 13 , 14 . Previous studies have reported the inhibitory effects of polyphyllin VII on the proliferation and apoptosis induction of different types of cancer cells, including human lung cancer cells (A549 and NCI-H1299 cells), human oral cancer cells (SAS and OECM-1 cells), human liver cancer cells (HepG2 cells), human nasopharyngeal cancer cells (HONE-1 and NPC-039 cells) and human colorectal cancer cells (HCT-116 and HT-29 cells) 12 - 14 , 25 , 26 . In our study, we utilized our own established human lung cancer cell line CTC-TJH-01, which possesses metastatic capabilities, as well as the commercial lung cancer cell line H1975, to investigate the anticancer efficacy of polyphyllin VII.…”

Therapeutic effects on cancer of the active ingredients in rhizoma paridis

“…These results suggest that polyphyllin VII may induce autophagic cell death in HepG2 cells by inhibiting the PI3K/AKT/mTOR and activating the JNK pathways ( Zhang et al, 2016b ). Moreover, polyphyllin VII induced apoptosis and autophagy in human osteosarcoma U2OS cells by regulating the JNK pathway ( Li X. et al, 2021 ). Another study showed that polyphyllin VII promoted ROS production in HepG2 cells, leading to depolarization of mitochondrial membrane potential, upregulation of the Bax/BCL2 ratio and protein levels in cleaved forms of caspase-3, caspase-8, and caspase-9, and poly (ADP ribose) polymerase, which eventually led to apoptosis.…”