Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination.
Possible synergistic cytotoxic and apoptotic effects of gossypol with zoledronic acid on DU-145 cells were explored, along with the rationale behind any observed synergism due to the different apoptotic proteins involved. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 activity were measured to verify apoptosis. Human Apoptosis Array was used to evaluate apoptotic proteins. The synergistic cytotoxic combination treatment had a versatile effect on apoptotic proteins, through inhibition of anti-apoptotic proteins (including cIAP-1, cIAP-2, survivin, livin, claspin, p53, p21, PON-2 and heat shock proteins) and concurrently the induction of pro-apoptotic proteins (Bad, Bax, Fas, FADD, cleaved caspase-3 and p27). Both drugs had a minimal toxicity profile comparing to cytotoxic agents. Combination treatments targeting many pivotal apoptosis-related proteins may be a rationale option for treatment of prostate cancer.
Sanli
U A
UA
Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey.
Gorumlu
G
G
Erten
C
C
Gul
M K
MK
Cengiz
E
E
Kucukzeybek
Y
Y
Karaca
B
B
Atmaca
H
H
Uzunoglu
S
S
Karabulut
B
B
Uslu
R
R
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003272:Contraceptive Agents, Male / Q000494:pharmacology / Q000627:therapeutic use; D053938:DNA Fragmentation / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D006072:Gossypol / Q000494:pharmacology* / Q000627:therapeutic use; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077211:Zoledronic Acid
D051017:Apoptosis Regulatory Proteins; D050071:Bone Density Conservation Agents; D003272:Contraceptive Agents, Male; D004164:Diphosphonates; D006728:Hormones; D007093:Imidazoles; D000077211:Zoledronic Acid; D006072:Gossypol