Curcumin induces apoptosis and inhibits growth of orthotopic human non-small cell lung cancer xenografts.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality. Curcumin is involved in various biological pathways leading to inhibition of NSCLC growth. The purpose of this study was to evaluate the effect of curcumin on expression of nuclear factor κB-related proteins in vitro and in vivo and on growth and metastasis in an intralung tumor mouse model. H1975 NSCLC cells were treated with curcumin (0-50 μM) alone, or combined with gemcitabine or cisplatin. The effects of curcumin were evaluated in cell cultures and in vivo, using ectopic and orthotopic lung tumor mouse models. Twenty mice were randomly selected into two equal groups, one that received AIN-076 control diet and one that received the same food but with the addition of 0.6% curcumin 14 days prior to cell implantation and until the end of the experiment. To generate orthotopic tumor, lung cancer cells in Matrigel were injected percutaneously into the left lung of CD-1 nude mice. Western blot analysis showed that the expressions of IkB, nuclear p65, cyclooxygenase 2 (COX-2) and p-ERK1/2 were down-regulated by curcumin in vitro. Curcumin potentiated the gemcitabine- or cisplatin-mediated antitumor effects. Curcumin reduced COX-2 expression in subcutaneous tumors in vivo and caused a 36% decrease in weight of intralung tumors (P=.048) accompanied by a significant survival rate increase (hazard ratio=2.728, P=.036). Curcumin inhibition of COX-2, p65 expression and ERK1/2 activity in NSCLC cells was associated with decreased survival and increased induction of apoptosis. Curcumin significantly reduced tumor growth of orthotopic human NSCLC xenografts and increased survival of treated athymic mice. To evaluate the role of curcumin in chemoprevention and treatment of NSCLC, further clinical trials are required.
Laboratory of Herbal Medicine and Cancer Research, Institute of Oncology, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: Shaharl@tasmc.health.gov.il.
Shahar
S
Lev-Ari
Department of Pulmonology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel, affiliated to the Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Alex
A
Starr
Laboratory of Herbal Medicine and Cancer Research, Institute of Oncology, Tel-Aviv University, Tel-Aviv, Israel.
Sara
S
Katzburg
Laboratory of Herbal Medicine and Cancer Research, Institute of Oncology, Tel-Aviv University, Tel-Aviv, Israel.
Liron
L
Berkovich
Laboratory of Herbal Medicine and Cancer Research, Institute of Oncology, Tel-Aviv University, Tel-Aviv, Israel.
Adam
A
Rimmon
Laboratory of Herbal Medicine and Cancer Research, Institute of Oncology, Tel-Aviv University, Tel-Aviv, Israel.
Rami
R
Ben-Yosef
Laboratory of Herbal Medicine and Cancer Research, Institute of Oncology, Tel-Aviv University, Tel-Aviv, Israel.
Akiva
A
Vexler
Laboratory of Herbal Medicine and Cancer Research, Institute of Oncology, Tel-Aviv University, Tel-Aviv, Israel.
Ilan
I
Ron
Laboratory of Herbal Medicine and Cancer Research, Institute of Oncology, Tel-Aviv University, Tel-Aviv, Israel.
Gideon
G
Earon
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D003474:Curcumin
Apoptosis; Cisplatin; Curcumin; NSCLC; Synergistic effect