Abstract
Objective
Cervical cancer is the second most common female cancer worldwide, and it remains
a challenge to manage preinvasive and invasive lesions. Food-based cancer prevention
entities, such as black raspberries and their derivatives, have demonstrated a marked
ability to inhibit preclinical models of epithelial cancer cell growth and tumor formation.
Here, we extend the role of black raspberry-mediated chemoprevention to that of cervical
carcinogenesis.
Methods
Three human cervical cancer cell lines, HeLa (HPV16−/HPV18+, adenocarcinoma), SiHa
(HPV16+/HPV18−, squamous cell carcinoma) and C-33A (HPV16−/HPV18−, squamous cell carcinoma),
were treated with a lyophilized black raspberry ethanol extract (RO-ET) at 25, 50,
100 or 200 μg/ml for 1, 3 and 5 days, respectively. Cell proliferation was measured by WST1 (tetrazolium salt cleavage)
assays. Flow cytometry (propidium iodide and Annexin V staining) and fluorescence
microscopy analysis were used to measure apoptotic cell changes.
Results
We found that non-toxic levels of RO-ET significantly inhibited the growth of human
cervical cancer cells, in a dose-dependent and time-dependent manner to a maximum
of 54%, 52% and 67%, respectively (p<0.05). Furthermore, cell growth inhibition was persistent following short-term withdrawal
of RO-ET from the culture medium. Flow cytometry and fluorescence microscopy demonstrated
RO-ET-induced apoptosis in all cell lines.
Conclusion
Black raspberries and their bioactive components represent promising candidates for
future phytochemical-based mechanistic pathway-targeted cancer prevention strategies.
Highlights
- RO-ET inhibits growth of HeLa, SiHa and C-33A human cervical cancer cells.
- The growth inhibition is persistent following short-term withdrawal of RO-ET.
- RO-ET induces apoptosis in HeLa, SiHa and C-33A cells.
Keywords
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References
- Cancer facts & figures 2010.American Cancer Society, Atlanta (GA)2010
- Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids).Fed Proc. 1976; 35: 1332-1338
- Cancer chemoprevention: progress and promise.Eur J Cancer. 1999; 35: 2031-2038
- Recent advances in chemoprevention of cancer.Science. 1997; 278: 1073-1077
- Perspectives on cancer chemoprevention research and drug development.Adv Cancer Res. 2000; 78: 199-334
- Cancer chemoprevention: progress and promise.J Natl Cancer Inst. 1998; 90: 1514-1528
- Molecular targets for cancer chemoprevention.Nat Rev Drug Discov. 2009; 8: 213-225
- Chemoprevention of oral cancer by black raspberries.Anticancer Res. 2002; 22: 4005-4015
- Chemoprevention of esophageal tumorigenesis by dietary administration of lyophilized black raspberries.Cancer Res. 2001; 61: 6112-6119
- Effects of lyophilized black raspberries on azoxymethane-induced colon cancer and 8-hydroxy-2′-deoxyguanosine levels in the Fischer 344 rat.Nutr Cancer. 2001; 40: 125-133
- Anthocyanins in black raspberries prevent esophageal tumors in rats.Cancer Prev Res (Phila). 2009; 2: 84-93
- Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro.J Agric Food Chem. 2006; 54: 9329-9339
- Suppression of the tumorigenic phenotype in human oral squamous cell carcinoma cells by an ethanol extract derived from freeze-dried black raspberries.Nutr Cancer. 2006; 54: 58-68
- Inhibition of the growth of premalignant and malignant human oral cell lines by extracts and components of black raspberries.Nutr Cancer. 2005; 51: 207-217
- Antiproliferative activity of apples is not due to phenolic-induced hydrogen peroxide formation.J Agric Food Chem. 2003; 51: 1718-1723
- Identification of cyanidin glycosides as constituents of freeze-dried black raspberries which inhibit anti-benzo[a]pyrene-7,8-diol-9,10-epoxide induced NFkappaB and AP-1 activity.Carcinogenesis. 2006; 27: 1617-1626
- Chemoprevention and vaccines: a review of the nonsurgical options for the treatment of cervical dysplasia.Int J Gynecol Cancer. 2005; 15: 4-12
- Cervical cancer chemoprevention, vaccines, and surrogate endpoint biomarkers.Cancer. 2003; 98: 2044-2051
- Balancing life-style and genomics research for disease prevention.Science. 2002; 296: 695-698
- Dietary intakes of selected nutrients and food groups and risk of cervical cancer.Nutr Cancer. 2008; 60: 331-341
- Anticarcinogenic activity of strawberry, blueberry, and raspberry extracts to breast and cervical cancer cells.J Med Food. 2001; 4: 49-51
- Antiproliferative activity is predominantly associated with ellagitannins in raspberry extracts.Phytochemistry. 2007; 68: 218-228
- Antioxidant properties of Korean black raspberry wines and their apoptotic effects on cancer cells.J Sci Food Agric. 2009; 89: 970-977
- Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells.Nutr Cancer. 2009; 61: 816-826
- Staurosporine-induced apoptosis of HPV positive and negative human cervical cancer cells from different points in the cell cycle.Cell Death Differ. 2001; 8: 234-244
- (−)-Anonaine induces apoptosis through Bax- and caspase-dependent pathways in human cervical cancer (HeLa) cells.Food Chem Toxicol. 2008; 46: 2694-2702
- Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells.Cancer Epidemiol. 2011; 35: 272-278
- Concurrent sulforaphane and eugenol induces differential effects on human cervical cancer cells.Integr Cancer Ther. 2011; (DOI: 10.1177/1534735411400313)
- Aqueous cinnamon extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential.BMC Cancer. 2010; 10: 210-211
- Green tea compound in chemoprevention of cervical cancer.Int J Gynecol Cancer. 2010; 20: 617-624
- Results from a dose–response study using 3,3′-diindolylmethane in the K14-HPV16 transgenic mouse model: cervical histology.Cancer Prev Res (Phila). 2011; 4: 890-896
- Titanium salan complexes displays strong antitumor properties in vitro and in vivo in mice.PLoS One. 2011; 6: e17869
Article info
Publication history
Accepted:
July 15,
2011
Received:
March 31,
2011
Identification
Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
