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1.
J Nutr Biochem ; 25(8): 843-50, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24835302

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Curcumin/pharmacology , Lung Neoplasms/drug therapy , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor/drug effects , Cell Survival/drug effects , Cyclooxygenase 2/metabolism , Humans , Lung Neoplasms/pathology , Mice, Nude , NF-kappa B/metabolism , Xenograft Model Antitumor Assays
2.
BMC Complement Altern Med ; 13: 212, 2013 Aug 19.
Article in English | MEDLINE | ID: mdl-23957955

ABSTRACT

BACKGROUND: Fewer than 6% patients with adenocarcinoma of the pancreas live up to five years after diagnosis. Chemotherapy is currently the standard treatment, however, these tumors often develop drug resistance over time. Agents for increasing the cytotoxic effects of chemotherapy or reducing the cancer cells' chemo-resistance to the drugs are required to improve treatment outcome. Nuclear factor kappa B (NF-kB), a pro-inflammatory transcription factor, reportedly plays a significant role in the resistance of pancreatic cancer cells to apoptosis-based chemotherapy. This study investigated the effect of aqueous Moringa Oleifera leaf extract on cultured human pancreatic cancer cells - Panc-1, p34, and COLO 357, and whether it can potentiates the effect of cisplatin chemotherapy on these cells. METHODS: The effect of Moringa Oleifera leaf extract alone and in combination with cisplatin on the survival of cultured human pancreatic cancer cells was evaluated by XTT-based colorimetric assay. The distribution of Panc-1 cells in the cell cycle following treatment with Moringa leaf extract was evaluated by flow cytometry, and evaluations of protein levels were via immunoblotting. Data of cell survival following combined treatments were analyzed with Calcusyn software. RESULTS: Moringa Oleifera leaf extract inhibited the growth of all pancreatic cell lines tested. This effect was significant in all cells following exposure to ≥0.75 mg/ml of the extract. Exposure of Panc-1 cells to Moringa leaf extract induced an elevation in the sub-G1 cell population of the cell-cycle, and reduced the expression of p65, p-IkBα and IkBα proteins in crude cell extracts. Lastly, Moringa Oleifera leaf extract synergistically enhanced the cytotoxic effect of cisplatin on Panc-1 cells. CONCLUSION: Moringa Oleifera leaf extract inhibits the growth of pancreatic cancer cells, the cells NF-κB signaling pathway, and increases the efficacy of chemotherapy in human pancreatic cancer cells.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cisplatin/pharmacology , Moringa oleifera/chemistry , NF-kappa B/metabolism , Pancreatic Neoplasms/drug therapy , Plant Extracts/pharmacology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Down-Regulation/drug effects , Drug Synergism , Humans , NF-kappa B/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Plant Leaves/chemistry , Protein Biosynthesis/drug effects , Signal Transduction/drug effects
3.
Harefuah ; 151(11): 629-32, 654, 2012 Nov.
Article in Hebrew | MEDLINE | ID: mdl-23367734

ABSTRACT

The association between chronic inflammation and carcinogenesis, as well as neoplastic progression, has been researched and is well-established. Being a central coordinator of immune responses, nuclear factor-kappa B (NFkappaB) signaling plays a critical role in cancer development and progression. The activation of the NFkappaB signaling pathway is highly monitored under normal conditions, and is mainly known as a key pathway in activation of immune responses. Constitutively active NFkappaB has been identified in most tumor cell lines, as well as in a wide variety of tumor tissues derived from cancer patients. Such activation may also affect the cancer's response to therapy, making it less susceptive to radio and chemo treatment. Hence, NFkappaB has become a target for inhibition by chemotherapeutic agents. Traditionally, medicinal herbs have been used to prevent and treat a variety of diseases, including cancer. In this article, we review several natural, herbal-derived compounds shown to have anti-inflammatory and anticancer activities mediated, at least in part, by NFkappaB signaling inhibition. Compounds of this sort may potentially serve as clinically effective anticancer treatments.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Neoplasms/drug therapy , Plant Extracts/pharmacology , Anti-Inflammatory Agents/isolation & purification , Disease Progression , Humans , Inflammation/drug therapy , Inflammation/physiopathology , NF-kappa B/metabolism , Neoplasms/pathology , Neoplasms/prevention & control , Phytotherapy , Signal Transduction/drug effects
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