Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells

• Published in: International journal of molecular sciences 2019-10, Vol.20 (19), p.4891
• Main Authors: Katta, Shilpa, Srivastava, Arun, Thangapazham, Rajesh L, Rosner, Inger L, Cullen, Jennifer, Li, Hua, Sharad, Shashwat
• Format: Article
• Language: English
• Subjects: AKT protein; Androgen receptors; Androgens; Androgens - metabolism; Antineoplastic Agents - pharmacology; Apoptosis; Castration; Cell cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation - drug effects; Chemical compounds; Chemotherapy; Chromosomes; Clustering; Cocitation; Computational Biology - methods; Curcumin; Curcumin - pharmacology; Disease prevention; Ewings sarcoma; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene Ontology; Genes; Growth factors; Homology; Hormones - metabolism; Humans; Kinases; Lymphocytes B; Male; Metastases; Metastasis; Mortality; myc; Myc protein; NF-κB protein; Pharmacology; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proteins; PTEN protein; Rapamycin; Signal transduction; Signal Transduction - drug effects; signaling pathways; Tensin; tgf-β; TOR protein; Transcription factors; Transforming growth factor-b; Tumor necrosis factor-TNF; Wnt protein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20194891

The androgen receptor is one of the key targets for prostate cancer treatment. Despite its less satisfactory effects, chemotherapy is the most common treatment option for metastatic and/or castration-resistant patients. There are constant needs for novel anti-prostate cancer therapeutic/prevention agents. Curcumin, a known chemo-preventive agent, was shown to inhibit prostate cancer cell growth. This study aimed to unravel the inhibitory effect of curcumin in prostate cancer through analyzing the alterations of expressions of curcumin targeting genes clusters in androgen-dependent LNCaP cells and androgen-independent metastatic C4-2B cells. Hierarchical clustering showed the highest number of differentially expressed genes at 12 h post treatment in both cells, suggesting that the androgen-dependent/independent manner of curcumin impacts on prostate cancer cells. Evaluation of significantly regulated top canonical pathways highlighted that Transforming growth factor beta (TGF-β), Wingless-related integration site (Wnt), Phosphoinositide 3-kinase/Protein Kinase B/ mammalian target of rapamycin (PIK3/AKT(PKB)/mTOR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling were primarily inhibited, and Phosphatase and tensin homolog (PTEN) dependent cell cycle arrest and apoptosis pathways were elevated with curcumin treatment. The short term (3-24 h) and long term (48 h) effect of curcumin treatment revealed 31 and four genes modulated in both cell lines. TGF-β signaling, including the androgen/TGF-β inhibitor Prostate transmembrane protein androgen-induced 1 ( ), was the only pathway impacted by curcumin treatment after 48 h. Our findings also established that Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. This study established, for the first time, novel gene-networks and signaling pathways confirming the chemo-preventive and cancer-growth inhibitory nature of curcumin as a natural anti-prostate cancer compound.