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Triphala inhibits both in vitro and in vivo xenograft growth of pancreatic tumor cells by inducing apoptosis.
- Source :
-
BMC cancer [BMC Cancer] 2008 Oct 10; Vol. 8, pp. 294. Date of Electronic Publication: 2008 Oct 10. - Publication Year :
- 2008
-
Abstract
- Background: Triphala is commonly used in Ayurvedic medicine to treat variety of diseases; however its mechanism of action remains unexplored. This study elucidates the molecular mechanism of Triphala against human pancreatic cancer in the cellular and in vivo model.<br />Methods: Growth-inhibitory effects of Triphala were evaluated in Capan-2, BxPC-3 and HPDE-6 cells by Sulphoradamine-B assay. Apoptosis was determined by cell death assay and western blotting. Triphala was administered orally to nude mice implanted with Capan-2 xenograft. Tumors were analyzed by immunohistochemistry and western blotting.<br />Results: Exposure of Capan-2 cells to the aqueous extract of Triphala for 24 h resulted in the significant decrease in the survival of cells in a dose-dependent manner with an IC50 of about 50 microg/ml. Triphala-mediated reduced cell survival correlated with induction of apoptosis, which was associated with reactive oxygen species (ROS) generation. Triphala-induced apoptosis was linked with phosphorylation of p53 at Ser-15 and ERK at Thr-202/Tyr-204 in Capan-2 cells. Above mentioned effects were significantly blocked when the cells were pretreated with an antioxidant N-acetylcysteine (NAC), suggesting the involvement of ROS generation. Pretreatment of cells with pifithrin-alpha or U0126, specific inhibitors of p53 or MEK-1/2, significantly attenuated Triphala-induced apoptosis. Moreover, NAC or U0126 pretreatment significantly attenuated Triphala-induced p53 transcriptional activity. Similarly, Triphala induced apoptosis in another pancreatic cancer cell line BxPC-3 by activating ERK. On the other hand, Triphala failed to induce apoptosis or activate ERK or p53 in normal human pancreatic ductal epithelial (HPDE-6) cells. Further, oral administration of 50 mg/kg or 100 mg/kg Triphala in PBS, 5 days/week significantly suppressed the growth of Capan-2 pancreatic tumor-xenograft. Reduced tumor-growth in Triphala fed mice was due to increased apoptosis in the tumors cells, which was associated with increased activation of p53 and ERK.<br />Conclusion: Our preclinical studies demonstrate that Triphala is effective in inhibiting the growth of human pancreatic cancer cells in both cellular and in vivo model. Our data also suggests that the growth inhibitory effects of Triphala is mediated by the activation of ERK and p53 and shows potential for the treatment and/or prevention of human pancreatic cancer.
- Subjects :
- Animals
Antineoplastic Agents therapeutic use
Cell Line, Tumor
Cell Survival drug effects
DNA Damage
Enzyme Activation
Enzyme-Linked Immunosorbent Assay
Extracellular Signal-Regulated MAP Kinases genetics
Extracellular Signal-Regulated MAP Kinases metabolism
Humans
Immunohistochemistry
Mice
Neoplasm Transplantation
Pancreas metabolism
Pancreas pathology
Pancreatic Neoplasms drug therapy
Pancreatic Neoplasms metabolism
Plant Extracts therapeutic use
Reactive Oxygen Species metabolism
Transplantation, Heterologous
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
Antineoplastic Agents pharmacology
Apoptosis drug effects
Pancreatic Neoplasms pathology
Plant Extracts pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2407
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- BMC cancer
- Publication Type :
- Academic Journal
- Accession number :
- 18847491
- Full Text :
- https://doi.org/10.1186/1471-2407-8-294