PPT1 Reduction Contributes to Erianin-Induced Growth Inhibition in Oral Squamous Carcinoma Cells

Abstract

The anticancer properties of erianin have been recently discovered. However, the antitumor effect of erianin in oral squamous cell carcinoma (OSCC) remains unclear. In this study, we demonstrated that erianin can hamper OSCC cells growth both in vitro and in vivo. Erianin induced obvious G2/M arrest as well as apoptosis and gasdermin E (GSDME)-dependent pyroptosis in OSCC cells. Moreover, erianin increased autophagosome formation but decreased autolysosome function. Further study indicated that erianin significantly suppressed the expression of protein-palmitoyl thioesterase 1 (PPT1) and mTOR signaling. PPT1 has been reported to be a critical regulator of cancer progression by its modulation of autophagy and mTOR signaling. According to online databases, higher expression of PPT1 has been observed in OSCC tissues and is associated with poorer patient prognosis. As overexpression of PPT1 significantly reversed erianin-induced growth inhibition in OSCC cells, we identified the importance of PPT1 reduction in erianin-induced growth suppression. With the xenograft model, we confirmed the antitumor effect of erianin in vivo. Erianin efficiently decreased the tumor sizes, together with visibly reduced expression of PPT1 and phosphorylation of mTOR in the xenograft tumor tissues. Therefore, the present study indicated that erianin may be potentially used in OSCC therapy.

ROS-dependent palmitoylation is an obligate licensing modification for GSDMD pore formation

“…Specifically, palmitoylation was detected at GSDME-NT, which is different from the previously reported GSDME-CT palmitoylation ( 24 ) . Since CT is not part of the transmembrane pore, we propose that the observed inhibition of chemotherapy-induced pyroptosis by 2-BP ( 24 ) is from its effect on GSDME-NT, and the GSDME-dependent anticancer effect of Erianin is through suppression of a depalmitoylase that enzymatically removes the palmitate ( 28 ). These data suggest that palmitoylation, possibly all at GSDM-NTs, is an obligate requirement for GSDM pore formation.…”

Exploring beyond Common Cell Death Pathways in Oral Cancer: A Systematic Review

“…Among the selected studies, 46 studies evaluated ferroptosis , 22 studies focused on pyroptosis [28,33,[64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83], 8 studies on necroptosis [84][85][86][87][88][89][90][91] and 5 studies on other types of cell death [92][93][94][95][96]. One study [28] explored both ferroptosis and pyroptosis, Among the selected studies, 46 studies evaluated ferroptosis , 22 studies focused on pyroptosis [28,33,[64][65][66][67][68][69][70][71][72][73]…”

“…Pyroptosis, as a form of lytic cell death, amplifies the release of mature interleukin-1 (IL-1) and interleukin-18 (IL-18), potentially influencing the development of cancer [151]. Furthermore, pyroptosis serves as the mechanism for inflammatory cell death in cancer cells, thereby restraining the proliferation and migration of these cancer cells [28,33,[68][69][70]78,79]. Consequently, pyroptosis assumes a dual role, both promoting and inhibiting tumorigenesis [152].…”

Mechanism of Erianin anti-triple negative breast cancer based on transcriptomics methods and network pharmacology

“…When the tumor size reached approximately 15 mm 3 , all mice were randomly divided into two groups: the experimental group and the control group (five mice in each group). The mice in the experimental group were injected with 4 mg/kg Erianin (based on previous studies [9,12,[18][19][20][21][22][23] and our experimental validation), while the control group received an injection of the same volume of 1% DMSO. Every two days, the tumor volume was measured.…”