Therapeutic efficacy of curcumin/TRAIL combination regimen for hormone-refractory prostate cancer.
Because of lack of effective treatment options for hormone-refractory prostate cancer at the present time, the need for developing novel therapeutic strategies and targets to treat and prevent the progression of hormone-sensitive prostate cancer to the hormone-refractory stage is paramount. Our previous in vitro studies have shown that curcumin sensitizes both hormone-sensitive and hormone-resistant prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and that combined curcumin/TRAIL treatment induces apoptosis in cancer cells by inhibiting antiapoptotic p-Akt and nuclear factor-kappaB (NF-kappaB). In the present study, we demonstrate that curcumin and TRAIL combination regimen is also the most effective treatment for inhibiting the growth of PC3 xenografts compared to curcumin or TRAIL monotherpy. The inhibition of PC3 tumors by combined treatment correlated with significant reduction in expression of p-Akt and NF-kappaB in tumor tissue. Furthermore, tumor growth inhibition by curcumin/TRAIL combination regimen was associated with significant decrease in cell proliferation and an increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the tumors without significant change in microvessel density. Based on the significant efficacy in this preclinical model, combined curcumin/TRAIL regimen may be an effective adjuvant therapy for hormone-refractory prostate cancer.
Andrzejewski
Tanja
T
Department of Surgery, Henry Ford Health System, Detroit, MI, USA.
Deeb
Dorrah
D
Gao
Xiaohua
X
Danyluk
Andrew
A
Arbab
Ali S
AS
Dulchavsky
Scott A
SA
Gautam
Subhash C
SC
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D018931:Antineoplastic Agents, Hormonal; D016328:NF-kappa B; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin