(E)-2,4-Bis(p-hydroxyphenyl)-2-butenal enhanced TRAIL-induced apoptosis in ovarian cancer cells through downregulation of NF-κB/STAT3 pathway

Abstract

Ovarian cancer is a cancerous growth arising from the ovary and with poor prognosis that usually have resistant to all currently available treatments. Whether (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (butenal) synthesized by Maillard reaction from fructose-tyrosine, has potential therapeutic activity against human ovarian cancer was investigated using two ovarian cancer cell lines (PA-1, SK-OV-3). We found that butenal could inhibit NF-κB/STAT3 activity, thereby inducing apoptotic cell death of ovarian cancer cells. We treated with several concentration of butenal each cell line differently (PA-1; 5, 10 and 15 μg/ml, SK-OV-3; 10, 20 and 30 μg/ml). First, ovarian cancer cell lines exhibited constitutively active NF-κB, and treatment with butenal abolished this activation as indicated by DNA binding activity. Second, butenal suppressed activation of signal transducer and activator of transcription-3 as indicated by decreased phosphorylation and inhibition of Janus kinase-2 phosphorylation. Third, butenal induced expression of pro-apoptotic proteins such as proteolytic cleavage of PARP, Bax and activation of caspase-3, -8 and -9. Lastly, combination of butenal and TRAIL causes enhanced induction of apoptosis. Overall, our results indicate that butenal mediates its anti-proliferative and apoptotic effects through activation of multiple cell signaling pathways and enhances the TRAIL-induced apoptosis. These data suggested that butenal may be a potential anti-cancer agent in ovarian cancer.

(E)‐2‐methoxy‐4‐(3‐(4‐methoxyphenyl)prop‐1‐en‐1‐yl)phenol suppresses ovarian cancer cell growth via inhibition of ERK and STAT3

“…16 CCDO-Me, a synthetic triterpenoid, inhibits expression of STAT3 phosphorylation in multi-drug resistant ovarian cancer cells. 17 Similarly, in our previous study, we found that (E)-2,4-bis (p-hydroxyphenyl)-2-butenal enhanced TRAIL-induced apoptosis in ovarian cancer cells via down regulation of STAT3 pathway, 18 bee venom toxin and melittin suppressed ovarian cancer cell growth through induction of death receptors and inhibition of STAT3 pathway. 19 Moreover, it was demonstrated that blocking STAT3 activation with shRNA or siRNA could suppress ovarian cancer cell growth.…”

“…A novel oncolytic adenovirus, a STAT3 inhibitor HO‐3867 and a synthetic triterpenoid CCDO‐Me showed inhibitory effect on cancer cell growth via blocking STAT3 signaling pathway in ovarian cancer . In our previous study, we also found that (E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal, snake venom toxin, bee venom suppressed ovarian cancer cell growth via inhibition of STAT3 …”

“…[15][16][17] In our previous study, we also found that (E)-2,4-bis (p-hydroxyphenyl)-2-butenal, snake venom toxin, bee venom suppressed ovarian cancer cell growth via inhibition of STAT3. [18][19][20] Mitogen-activated protein kinase (MAPK) pathway consist of p38 MAPK (p38), ERK, and JNK. Activation of MAPK pathway plays a vital role in survival, growth arrest, and programmed cell death signalling event.…”

Novel synthetic (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol inhibits arthritis by targeting signal transducer and activator of transcription 3

“…We previously identified BHPB, a tyrosine-fructose MR product as a STAT3 inhibitor, which has potential therapeutic properties against multiple diseases including RA15161718192021222333. Despite its multiple pharmacological properties, the major drawback of BHPB in drug development is its lack of drug-likeness properties and limited chemical stability.…”

“…This action mediates the potent therapeutic effects of BHPB against RA14 as well as Alzheimer’s disease151617, and tumour growth181920212223. However, its drug-likeness is not relevant for drug development because it has a low chemical stability, low solubility, and high toxicity.…”