Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice
Top Cited Papers
Open Access
- 28 September 2004
- journal article
- early detection-and-diagnosis
- Published by Wiley in International Journal of Cancer
- Vol. 113 (3) , 423-433
- https://doi.org/10.1002/ijc.20587
Abstract
Chemoprevention has come of age as an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. We argue that agents capable of intervening at more than one critical pathway in the carcinogenesis process will have greater advantage over other single‐target agents. Pomegranate fruit extract (PFE) derived from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. Pomegranate fruit was extracted with acetone and analyzed based on matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry and found to contain anthocyanins, ellagitannins and hydrolyzable tannins. We evaluated whether PFE possesses antitumor‐promoting effects. We first determined the effect of topical application of PFE to CD‐1 mice against 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced conventional markers and other novel markers of skin tumor promotion. We found that topical application of PFE (2 mg/mouse) 30 min prior to TPA (3.2 nmole/mouse) application on mouse skin afforded significant inhibition, in a time‐dependent manner, against TPA‐mediated increase in skin edema and hyperplasia, epidermal ornithine decarboxylase (ODC) activity and protein expression of ODC and cyclooxygenase‐2. We also found that topical application of PFE resulted in inhibition of TPA‐induced phosphorylation of ERK1/2, p38 and JNK1/2, as well as activation of NF‐κB and IKKα and phosphorylation and degradation of IκBα. We next assessed the effect of skin application of PFE on TPA‐induced skin tumor promotion in 7,12‐dimethylbenz(a)anthracene‐initiated CD‐1 mouse. The animals pretreated with PFE showed substantially reduced tumor incidence and lower tumor body burden when assessed as total number of tumors per group, percent of mice with tumors and number of tumors per animal as compared to animals that did not receive PFE. In TPA‐treated group, 100% of the mice developed tumors at 16 weeks on test, whereas at this time in PFE‐treated group, only 30% mice exhibited tumors. Skin application of PFE prior to TPA application also resulted in a significant delay in latency period from 9 to 14 weeks and afforded protection when tumor data were considered in terms of tumor incidence and tumor multiplicity. The results of our study provide clear evidence that PFE possesses antiskin‐tumor‐promoting effects in CD‐1 mouse. Because PFE is capable of inhibiting conventional as well as novel biomarkers of TPA‐induced tumor promotion, it may possess chemopreventive activity in a wide range of tumor models. Thus, an in‐depth study to define active agent(s) in PFE capable of affording antitumor‐promoting effect is warranted.Keywords
This publication has 96 references indexed in Scilit:
- Clinical Grade Purification and Expansion of NK Cell Products for an Optimized Manufacturing ProtocolFrontiers in Oncology, 2013
- Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centersBone Marrow Transplantation, 2012
- Natural killer cell engineering for cellular therapy of cancerTissue Antigens, 2011
- IL-2 Stimulated but Not Unstimulated NK Cells Induce Selective Disappearance of Peripheral Blood Cells: Concomitant Results to a Phase I/II StudyPLOS ONE, 2011
- NKAML: A Pilot Study to Determine the Safety and Feasibility of Haploidentical Natural Killer Cell Transplantation in Childhood Acute Myeloid LeukemiaJournal of Clinical Oncology, 2010
- High Log-Scale Expansion of Functional Human Natural Killer Cells from Umbilical Cord Blood CD34-Positive Cells for Adoptive Cancer ImmunotherapyPLOS ONE, 2010
- Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activationBlood, 2008
- Reciprocal activating interaction between 6‐sulfo LacNAc+ dendritic cells and NK cellsInternational Journal of Cancer, 2008
- Cancer chemoprevention with dietary phytochemicalsNature Reviews Cancer, 2003
- Nuclear transcription factor-κB as a target for cancer drug developmentLeukemia, 2002