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. 2013 Aug 19;13:212.
doi: 10.1186/1472-6882-13-212.

Moringa Oleifera Aqueous Leaf Extract Down-Regulates Nuclear factor-kappaB and Increases Cytotoxic Effect of Chemotherapy in Pancreatic Cancer Cells

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Free PMC article

Moringa Oleifera Aqueous Leaf Extract Down-Regulates Nuclear factor-kappaB and Increases Cytotoxic Effect of Chemotherapy in Pancreatic Cancer Cells

Liron Berkovich et al. BMC Complement Altern Med. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Effect of Moringa Oleifera leaf extract on the viability of Panc-1, COLO 357 and p34 pancreatic cancer cells. The cells were plated in 96-well plates and treated in triplicates with Moringa Oleifera leaf extract for 3 days. Cell survival was assessed using XTT-based cell proliferation assay, and is indicated after normalization to the control group. The significance of the effect is indicated as *p ≤ 0.05 and **p ≤ 0.001.
Figure 2
Figure 2
Effect of Moringa Oleifera leaf extract on the distribution of Panc-1 cells in the cell cycle. (A) Representative histograms of cell distribution following Moringa Oleifera leaf extract treatments. (B) Data summarized from three independent experiments (%). The cells were treated with the extract for 24 hours, collected, washed and fixed in 70% ice-cold ethanol. Prior to the analysis, the cells were suspended in 0.1% Triton-X with 30 mg/ml DNAse-free RNAse A for 6 hrs. Propidium iodide was added several minutes before cell analysis by flow cytometry. The significance of the effect, relatively to non-treated cells (control), is indicated as *p ≤ 0.05 and **p ≤ 0.001.
Figure 3
Figure 3
Effect of Moringa Oleifera leaf extract on the expression of p65 NF-kB, IkB and p-IkB proteins in Panc-1. (A) Protein expressions in crude lysates of the cells treated with Moringa Oleifera leaf extract (0–1.5 mg/mL) for 24 hours. (B) Expression of p65 in nuclear extracts of the cells treated with Moringa Oleifera leaf extract. Protein expression was analyzed by Western blot. GAPDH and ß-actin were used to demonstrate the quantity of standard proteins in the samples tested.
Figure 4
Figure 4
Combined treatments effect of Moringa Oleifera leaf extract with cisplatin on the viability of Panc-1 cells. (A) Cell viability following treatments of Moringa Oleifera leaf extract, cisplatin and combined treatments of increasing concentrations of the extract and cisplatin for 3 days. (B) Normalized isobologram of Moringa Oleifera leaf extract with cisplatin treatments shown in compound A. (C) Median-effect plot curve of Moringa Oleifera leaf extract, cisplatin and Moringa Oleifera leaf extract with cisplatin shown in compound A. The cells were treated with each agent alone or in combination for 3 days. Cell viability was evaluated using XTT-based cell proliferation assay. Data was analyzed by Calcusyn software.

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References

    1. Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981–2002. J Nat Prod. 2003;66:1022–1037. doi: 10.1021/np030096l. - DOI - PubMed
    1. Hariharan D, Saied A, Kocher HM. Analysis of mortality rates for pancreatic cancer across the world. HPB (Oxford) 2008;10:58–62. doi: 10.1080/13651820701883148. - DOI - PMC - PubMed
    1. Oberstein PE, Wasif Saif M. First-line treatment for advanced pancreatic cancer. J Pancreas (Online) 2011;12:96–100. - PubMed
    1. Greenhalf W, Thomas A. Combination therapy for the treatment of pancreatic cancer. Anticancer Agents Med Chem. 2011;11:418–426. doi: 10.2174/187152011795677391. - DOI - PubMed
    1. Karin M, Lin A. NF-kappaB at the crossroads of life and death. Nat Immunol. 2002;3:221–227. - PubMed

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