Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo

Abstract

Erianin, a natural product derived from Dendrobium chrysotoxum, has exhibited potential antitumor activity in various malignancies, including hepatocarcinoma, melanoma, and promyelocytic leukemia. Here we explored the effects of erianin on osteosarcoma (OS) in vitro and in vivo and further elucidated the underlying molecule mechanisms. In this study, we found that erianin potently suppressed cell viability in various OS cell lines. Treatment with erianin induced G2/M-phase arrest, apoptosis, and autophagy in OS cells. Further studies showed that erianin-induced apoptosis and autophagy was attributed to reactive oxygen species (ROS), as N-acetyl cysteine (NAC), an ROS scavenger, attenuated them. Moreover, we found that erianin induced activation of c-Jun N-terminal kinase (JNK) signal pathway, which was also blocked by NAC. Downregulation of JNK by its specific inhibitor SP600125 could attenuate apoptosis and autophagy induced by erianin. Finally, erianin in vivo markedly reduced the growth with little organ-related toxicity. In conclusion, erianin induced cell cycle G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human OS. In light of these results, erianin may be a promising agent for anticancer therapy against OS.

Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma

“…Natural bioactive compounds derived from traditional Chinese medicinal herbs have been widely investigated because of their antiproliferative, antiangiogenic, and antitumor effects on various diseases, as well as their safety, efficacy and immediate availability. The effects of natural compounds on the inhibition of osteosarcoma have previously been reported by our research team . For instance, we found that pectolinarigenin significantly suppressed osteosarcoma cell proliferation, induced apoptosis and inhibited migration and invasion in osteosarcoma cells .…”

“…Alternol, a novel compound purified from microbial fermentation products, not only inhibited osteosarcoma cell proliferation and migration and induced caspase‐dependent apoptosis and G2/M cell cycle arrest in vitro, but also suppressed tumor growth in an orthotopic tibial osteosarcoma model . In addition, our team has demonstrated that two natural compounds, toosendanin and erianin, suppress human osteosarcoma growth and metastasis . The results of the present research indicate that RA, a natural bioactive compound, significantly suppressed cell proliferation and induced apoptosis in a dose‐ and time‐dependent method.…”

“…We found that RA significantly reduced cell proliferation, blocked clone for- The effects of natural compounds on the inhibition of osteosarcoma have previously been reported by our research team. [25][26][27]36 For instance, we found that pectolinarigenin significantly suppressed osteosarcoma cell proliferation, induced apoptosis and inhibited migration and invasion in osteosarcoma cells. 26 Alternol, a novel compound purified from microbial fermentation products, not only inhibited osteosarcoma cell proliferation and migration and induced caspase-dependent apoptosis and G2/M cell cycle arrest in vitro, but also suppressed tumor growth in an orthotopic tibial osteosarcoma model.…”

PTEN Activation by DNA Damage Induces Protective Autophagy in Response to Cucurbitacin B in Hepatocellular Carcinoma Cells

“…This crosstalk could be mediated by the interactions between Beclin-1 and Bcl-2/Bcl-xL and between FADD and Atg5, caspase- and calpain-mediated cleavage of autophagy-related proteins, and autophagic degradation of caspases [9–13]. Reactive oxygen species (ROS) plays important roles in mediating apoptosis and autophagy in response to a panel of natural products such as evodiamine [14], oridonin [15], graveoline [16], total tanshinones [17], and erianin [18]. …”

Phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog as therapeutic targets in breast cancer

“…144 Schmid et al 145 reported the substantially greater potency of bpV (phen), bpV (pic), and bpV (HOpic) against PTEN than against the classical protein tyrosine phosphatases (PTPs), protein tyrosine phosphatase 1B (PTP1B), and protein tyrosine phosphatase B (PTPb). Moreover, they detected a bpV-mediated enhancement of insulin-stimulated AKT activation that was observed in cells expressing 154,155 SF1126 (LY294002) LY294002 is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5/0.57/0.97 µM in cell-free assays, respectively, more stable in solution than Wortmannin, and also blocks autophagosome formation Mbengue et al, 156 Bolen et al, 157 Sapey et al 158 XL147 XL147 analogue is a selective and reversible class I PI3K inhibitor for PI3Kα/δ/γ with IC50 of 39/36/23 nM in cell-free assays, less potent to PI3Kβ. Phase 1/2…”