Triptolide Induces Growth Inhibition and Apoptosis of Human Laryngocarcinoma Cells by Enhancing p53 Activities and Suppressing E6-Mediated p53 Degradation

Abstract

Triptolide, an active compound extracted from Chinese herb Leigongteng (Tripterygium wilfordii Hook F.), shows a broad-spectrum of anticancer activity through its cytotoxicity. However, the efficacy of triptolide on laryngocarcinoma rarely been evaluated, and the mechanism by which triptolide-induced cellular apoptosis is still not well understood. In this study, we found that triptolide significantly inhibited the laryngocarcinoma HEp-2 cells proliferation, migration and survivability. Triptolide induces HEp-2 cell cycle arrest at the G1 phase and apoptosis through intrinsic and extrinsic pathways since both caspase-8 and -9 are activated. Moreover, triptolide enhances p53 expression by increasing its stability via down-regulation of E6 and E6AP. Increased p53 transactivates down-stream target genes to initiate apoptosis. In addition, we found that short time treatment with triptolide induced DNA damage, which was consistent with the increase in p53. Furthermore, the cytotoxicity of triptolide is decreased by p53 knockdown or use of caspases inhibitor. In conclusion, our results demonstrated that triptolide inhibits cell proliferation and induces apoptosis in laryngocarcinoma cells by enhancing p53 expression and activating p53 functions through induction of DNA damage and suppression of E6 mediated p53 degradation. These studies indicate that triptolide is a potential anti-laryngocarcinoma drug.

Triptolide inhibits transforming growth factor‐β1‐induced proliferation and migration of rat airway smooth muscle cells by suppressing nuclear factor‐κB but not extracellular signal‐regulated kinase 1/2

“…Triptolide (PG‐490), which is a diterpenoid triepoxide purified from a Chinese herb Tripterygium wilfordii Hook F, is the major component responsible for the immunosuppressive and anti‐inflammatory effects of T. wilfordii . Besides, triptolide has the effects of inhibiting proliferation and inducing apoptosis . We confirmed that triptolide inhibited airway remodelling in ovalbumin‐sensitized mice in our previous work .…”

“…Besides, triptolide has the effects of inhibiting proliferation and inducing apoptosis. 7,8 We confirmed that triptolide inhibited airway remodelling in ovalbumin-sensitized mice in our previous work. 9 However, the mechanism of how triptolide affects airway remodelling remains unclear.…”

Triptolide inhibits TGF-β1-induced cell proliferation in rat airway smooth muscle cells by suppressing Smad signaling

“…Besides, triptolide has the effects of inhibiting proliferation and inducing apoptosis [5][6][7]. We have confirmed that triptolide inhibited airway remodeling in OVA-sensitized mice [8].…”

Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells

“…Furthermore, the anti-cancer effect of TPL is attributed to its cytotoxicity. We found that TPL is cytotoxic to both cancer cells and normal cells in vitro , although the cytotoxic effect of TPL on normal cells is less than on cancer cells 53. The toxicity of TPL is dose-dependent.…”