PMID- 31581661 OWN - NLM STAT- MEDLINE DCOM- 20200212 LR - 20211204 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 19 DP - 2019 Oct 2 TI - Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells. LID - 10.3390/ijms20194891 [doi] LID - 4891 AB - 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-beta), 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-beta signaling, including the androgen/TGF-beta inhibitor Prostate transmembrane protein androgen-induced 1 (PMEPA1), was the only pathway impacted by curcumin treatment after 48 h. Our findings also established that MYC 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. FAU - Katta, Shilpa AU - Katta S AD - Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. shilpa.katta@nih.gov. AD - Henry Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. shilpa.katta@nih.gov. FAU - Srivastava, Arun AU - Srivastava A AD - Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. aruns1207@gmail.com. FAU - Thangapazham, Rajesh L AU - Thangapazham RL AD - Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. rajeshlt@gmail.com. AD - Henry Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. rajeshlt@gmail.com. FAU - Rosner, Inger L AU - Rosner IL AD - Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. inger.l.rosner.mil@mail.mil. AD - Department of Urology, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD 20889, USA. inger.l.rosner.mil@mail.mil. FAU - Cullen, Jennifer AU - Cullen J AD - Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. jcullen@cpdr.org. AD - Henry Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. jcullen@cpdr.org. FAU - Li, Hua AU - Li H AD - Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. hli@cpdr.org. AD - Henry Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. hli@cpdr.org. FAU - Sharad, Shashwat AU - Sharad S AD - Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. ssharad@cpdr.org. AD - Henry Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr., Suite 300, Bethesda, MD 20817, USA. ssharad@cpdr.org. LA - eng GR - HU001-004-c-1502 to DGM/Center for Prostate Disease Research Program, Uniformed Services University for the Health Sciences/ PT - Journal Article DEP - 20191002 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Androgens) RN - 0 (Antineoplastic Agents) RN - 0 (Hormones) RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - IT942ZTH98 (Curcumin) SB - IM MH - Androgens/metabolism MH - Antineoplastic Agents/*pharmacology MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation/drug effects MH - Computational Biology/methods MH - Curcumin/*pharmacology MH - Gene Expression Profiling MH - Gene Expression Regulation/*drug effects MH - Gene Ontology MH - Hormones/*metabolism MH - Humans MH - Male MH - Prostatic Neoplasms/genetics/metabolism/pathology MH - Proto-Oncogene Mas MH - Signal Transduction/drug effects PMC - PMC6801832 OTO - NOTNLM OT - AR OT - MYC OT - TGF-beta OT - chemotherapy OT - curcumin OT - metastasis OT - prostate cancer OT - signaling pathways COIS- The authors declare no conflict of interest. EDAT- 2019/10/05 06:00 MHDA- 2020/02/13 06:00 PMCR- 2019/10/01 CRDT- 2019/10/05 06:00 PHST- 2019/09/09 00:00 [received] PHST- 2019/09/25 00:00 [revised] PHST- 2019/09/29 00:00 [accepted] PHST- 2019/10/05 06:00 [entrez] PHST- 2019/10/05 06:00 [pubmed] PHST- 2020/02/13 06:00 [medline] PHST- 2019/10/01 00:00 [pmc-release] AID - ijms20194891 [pii] AID - ijms-20-04891 [pii] AID - 10.3390/ijms20194891 [doi] PST - epublish SO - Int J Mol Sci. 2019 Oct 2;20(19):4891. doi: 10.3390/ijms20194891.