Brucea javanica oil emulsion suppresses tumor growth in human cervical cancer cells through inhibition of the E6 oncogene and induction of apoptosis

Ling Ye, Jian-Fu Zhao, Yi-Ming Wang, Wen-Hui Chen, Shen Qian, Zhong-Guo Zhou, Meng Xu

Abstract

Background: Brucea javanica oil emulsion (BJOE) is a traditional Chinese medicine with recognized antitumor effects in various cancers, but the effects and mechanisms of action of BJOE against cervical cancer need to be further studied. Herein, we investigated the effects of BJOE on the human papillomavirus (HPV)16-expressing human cervical cancer line SiHa and explored the possible underlying mechanisms.
Methods: Cell viability and apoptosis of SiHa cells treated with BJOE were assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and annexin V-fluorescein isothiocyanate (annexin V-FITC)/propidium iodide (PI) staining assays, respectively. Quantitative reverse transcription- polymerase chain reaction and Western blot analyses were performed to assess the expression levels of the E6 oncogene and key signaling molecules involved in apoptosis. A subcutaneous xenograft nude mouse model bearing SiHa cells was established and treated with BJOE through intraperitoneal injection. Tumor growth was monitored, and immunohistochemical analysis was performed.
Results: BJOE exhibited substantial cytotoxic effects in SiHa cells and significantly suppressed tumor growth in SiHa cell xenografts. BJOE inhibited E6 expression and induced apoptosis in vitro in a dose- dependent manner. BJOE-induced apoptosis was characterized by activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, BJOE induced phosphorylation of extracellular-signal regulated kinase (ERK) and inhibited the expression of nuclear factor-kappa B (NF-κB).
Conclusions: BJOE exerts a strong tumor-suppressive effect in SiHa cells in vitro and in vivo, likely caused by E6 inhibition and apoptosis induction achieved through the ERK/mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, supporting potential use of BJOE in cervical cancer treatment.

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