Androgen responsive and refractory prostate cancer cells exhibit distinct curcumin regulated transcriptome.
Curcumin (diferuloylmethane) is the major active component of turmeric and is being actively investigated for its anti-cancer properties. To better understand the biological mechanisms of the chemopreventive potential of curcumin in prostate cancer, we have evaluated curcumin regulated transcriptome in prostate cancer cells. Hierarchical clustering methods and functional classification of the Curcumin-Gene Expression Response (Cu-GER) showed temporal co-regulation of genes involved in oxidative stress response and growth signaling pathways. Interestingly, C4-2B, androgen independent metastatic prostate cancer cells exhibited attenuated Cu-GER response in comparison to parental androgen dependent and less aggressive LNCaP cells. Androgen Receptor (AR) regulated genes which play critical roles in normal growth and differentiation of the prostate gland, as well as in prostate cancer, were also a part of the Cu-GER. Of note, curcumin downregulated transcript encoded by the potentially causal TMPRSS2-ERG gene fusion, a common oncogenic alteration noted in 50-70% of prostate cancer patients. Further more, expression of EGFR and ERBB2 receptor were found to be downregulated in curcumin treated LNCaP and C4-2B cells. This report for the first time establishes novel features of Cu-GER in prostate cancer cells of varying tumorigenic phenotypes and provides potentially novel read-outs for assessing effectiveness of curcumin in prostate cancer and likely in other cancers. Importantly, new gene-networks identified here further delineate molecular mechanism(s) of action of curcumin in prostate cancer cells.
Thangapazham
Rajesh L
RL
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Shaheduzzaman
Syed
S
Kim
Kee-Hong
KH
Passi
Neena
N
Tadese
Atekelt
A
Vahey
Maryanne
M
Dobi
Albert
A
Srivastava
Shiv
S
Maheshwari
Radha K
RK
D000728:Androgens / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005562:Formazans / Q000032:analysis / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D008297:Male; D008954:Models, Biological; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D013778:Tetrazolium Salts / Q000032:analysis / Q000378:metabolism; D013997:Time Factors
D000728:Androgens; D000970:Antineoplastic Agents; D005562:Formazans; D013778:Tetrazolium Salts; C079782:MTT formazan; D006419:Heme Oxygenase (Decyclizing); D003474:Curcumin