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(E)‐2‐methoxy‐4‐(3‐(4‐methoxyphenyl)prop‐1‐en‐1‐yl)phenol suppresses ovarian cancer cell growth via inhibition of ERK and STAT3
Author(s) -
Zheng Jie,
Son Dong Ju,
Lee Hye Lim,
Lee Hee Pom,
Kim Tae Hoon,
Joo Jung Heun,
Ham Young Wan,
Kim Wun Jae,
Jung Jae Kyung,
Han SangBae,
Hong Jin Tae
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22648
Subject(s) - mapk/erk pathway , apoptosis , kinase , p38 mitogen activated protein kinases , cell growth , microbiology and biotechnology , stat3 , biology , ovarian cancer , caspase 3 , cancer research , transfection , cancer , cell culture , programmed cell death , biochemistry , genetics
In the present study, we synthesized several non‐aldehyde analogues of (E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal which showed anti‐cancer effect. Interestingly, among the 16 compounds, we found that (E)‐2‐methoxy‐4‐(3‐(4‐methoxyphenyl)prop‐1‐en‐1‐yl)phenol (MMPP) showed the most significant anti‐proliferative effect on PA‐1 and SK‐OV‐3 ovarian epithelial cancer cells. MMPP treatment (0‐15 µg/mL) induced apoptotic cell death, enhanced the expression of cleaved caspase‐3, and cleaved caspase‐9 in a concentration dependent manner. Notably, DNA binding activity of STAT3, phosphorylation of extracellular signal‐regulated kinase (ERK) and p38 was significantly decreased by MMPP treatment. However, ERK siRNA augmented MMPP‐induced inhibitory effect on cell growth rather than p38 siRNA or JNK siRNA. Moreover, combination treatment of MMPP with ERK inhibitor U0126 (10 µM) augmented MMPP‐induced inhibitory effect on cell growth and DNA binding activity of STAT3, and enhanced expression of cleaved caspase‐3 and cleaved caspase‐9. In addition, STAT3 siRNA transfection augmented MMPP‐induced cell growth inhibition. In PA‐1 bearing xenograft mice model, MMPP (5 mg/kg) suppressed tumor growth significantly. Immunohistochemistry staining showed that the expression levels of p‐ERK, PCNA, p‐STAT3 were decreased while the expression level of caspase‐3 was increased by MMPP treatment. Thus, MMPP may be a promising anti‐cancer agent in ovarian epithelial cancer treatment.