Betulinic Acid Inhibits Cell Proliferation in Human Oral Squamous Cell Carcinoma Via Modulating ROS-Regulated p53 Signaling.

Betulinic Acid Inhibits Cell Proliferation in Human Oral Squamous Cell Carcinoma Via Modulating ROS-Regulated p53 Signaling.

Oncol Res. 2017 Jan 20;:

Authors: Shen H, Liu L, Yang Y, Xun W, Wei K, Zeng G

Abstract
Oral squamous cell carcinoma (OSCC) is a common cancer of the head and neck. Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid. The present study was designed to explore the effects of BA on OSCC KB cell proliferation <em>in vitro</em> and implanted tumor growth <em>in vivo</em> and to examine the possible molecular mechanisms. The results showed that BA dose-dependently inhibited KB cell proliferation and decreased implanted tumor volume. In addition, BA significantly promoted mitochondrial apoptosis, as reflected by increase of TUNEL-positive cells and activities of caspase 3 and 9, increase of Bax expression and decrease of Bcl-2 expression and mitochondrial oxygen consumption rate. BA also significantly increased cell population in G0/G1 phase and decreases S phase cell number, indicating the occurrence of G0/G1 cell cycle arrest. ROS generation was significantly increased by BA and antioxidant NAC treatment markedly inhibited the effect of BA on apoptosis, cell cycle arrest, and proliferation. BA dose-dependently increased p53 expression in KB cells and implanted tumors. p53 reporter gene activity and p53 binding in the promoters of Bax were significantly increased by BA. Knock-down of p53 blocked BA-induced increase of apoptosis, cell cycle arrest and inhibition of cell proliferation. NAC treatment suppressed BA-induced increase of p53 expression. Furthermore, phosphorylation of signal transducer and activator of transcription 3 (STAT3) was increased by BA. Taken together, the data demonstrated that ROS-p53 signaling was crucial for BA-exhibited anti-tumor effect in OSCC. BA may serve as a potential drug for the treatment of oral cancer.

PMID: 28109089 [PubMed - as supplied by publisher]

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