Abstract
BackgroundFewer 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.MethodsThe 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.ResultsMoringa 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.ConclusionMoringa 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.
Highlights
The present study examined the effect of Moringa Oleifera aqueous leaf extract on the viability and cell cycle of cultured human pancreatic cancer cells, and evaluated its ability to modify the expression of key proteins of the Nuclear factor kappa B (NF-kB) signaling pathway
All cells were grown in Dulbecco modified Eagle medium (DMEM) supplemented by 10% heat-inactivated bovine serum, 4.5 g/L glucose, 200 μM L-glutamine, 10 units/ml penicillin and 10 μg/mL streptomycin (Biological Industries, Beit HaEmek, Israel)
For our survival experiments of cultured pancreatic cancer cells we started looking for an effect around 0.1 mg/mL and upraised it according to our results
Summary
Fewer than 6% patients with adenocarcinoma of the pancreas live up to five years after diagnosis. Adenocarcinoma of the pancreas, the most common form of pancreatic cancer, is the fourth commonest cause of cancer-related mortality worldwide [2] This cancer is often diagnosed at advanced stages and has a poor prognosis, with fewer than 6% of those patients living as long as five years after diagnosis [2]. The basis of current pancreatic cancer therapy is targeting DNA synthesis using gemcitabine, with or without a second agent like 5-FU or a platinum based agent [3]. This treatment is limited by a resistance of the cancer cells to these therapies as well as a somatic toxicity [4]. The drug resistance is attributed to several mechanisms: drugs exclusion from the cells, changes in the enzymes metabolizing the drugs, or the cells becoming more resistant to stress and apoptosis [4]
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