cardamonin and Prostatic-Neoplasms

The pleiotropic transcription factor, signal transducer and activator of transcription 3 (STAT3) is often aberrantly activated in a wide variety of cancers and plays a pivotal role in tumor initiation, promotion and progression. Targeting deregulated STAT3 activation by small molecule inhibitors is generally considered as an important therapeutic strategy. Hence, in the present study, we evaluated the potential of cardamonin (CD), a 2',4'-dihydroxy-6'-methoxychalcone, to modulate STAT3 activation in prostate cancer (PC) cells and found that this chalcone can indeed exhibit significant anticancer effects through negatively regulating STAT3 activation by diverse molecular mechanism(s). CD suppressed STAT3 phosphorylation, nuclear translocation and DNA binding ability in PC cells. Computational modeling revealed that CD can bind directly to the Src Homology 2 domain of STAT3 and also effectively inhibit its dimerization. CD was also found to significantly reduce the migratory/invasive potential of PC cells through the downregulation of various oncogenic proteins. Overall, the data indicates that the potential application of CD as a STAT3 blocker can mitigate both the growth and survival of PC cells.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Chalcones; Dimerization; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasm Invasiveness; Phosphorylation; Prostatic Neoplasms; Signal Transduction; STAT3 Transcription Factor

The Myrtaceae family is a common source of medicines used in the treatment of numerous diseases in South America. In Brazil, fruits of the Campomanesia species are widely used to make liqueurs, juices and sweets, whereas leaves are traditionally employed as a medicine for dysentery, stomach problems, diarrhea, cystitis and urethritis. Ethanol extracts of Campomanesia adamantium (Myrtaceae) leaves and fruits were evaluated against prostate cancer cells (PC-3). The compound (2E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3-phenylprop-2-en-1-one, cardamonin) was isolated from ethanol extracts of C. adamantium leaves in a bioactivity-guided study and quantified by UPLC-MS/MS. In vitro studies showed that the isolated chalcone cardamonin inhibited prostate cancer cell proliferation and decreased the expression of NFkB1. Moreover, analysis by flow cytometry showed that this compound induced DNA fragmentation, suggesting an effect on apoptosis induction in the PC-3 cell line.

Topics: Apoptosis; Brazil; Cell Line, Tumor; Cell Proliferation; Chalcone; Chalcones; Humans; Male; Myrtaceae; Plant Extracts; Prostatic Neoplasms