Cactus pear: a natural product in cancer chemoprevention.
BACKGROUND
Cancer chemoprevention is a new approach in cancer prevention, in which chemical agents are used to prevent cancer in normal and/or high-risk populations. Although chemoprevention has shown promise in some epithelial cancers, currently available preventive agents are limited and the agents are costly, generally with side effects. Natural products, such as grape seed, green tea, and certain herbs have demonstrated anti-cancer effects. To find a natural product that can be used in chemoprevention of cancer, we tested Arizona cactus fruit solution, the aqueous extracts of cactus pear, for its anti-cancer effects in cultured cells and in an animal model.


METHODS
Aqueous extracts of cactus pear were used to treat immortalized ovarian and cervical epithelial cells, as well as ovarian, cervical, and bladder cancer cells. Aqueous extracts of cactus pear were used at six concentrations (0, 0.5, 1, 5, 10 or 25%) to treat cells for 1, 3, or 5 days. Growth inhibition, apoptosis induction, and cell cycle changes were analyzed in the cultured cells; the suppression of tumor growth in nude mice was evaluated and compared with the effect of a synthetic retinoid N-(4-hydroxyphernyl) retinamide (4-HPR), which is currently used as a chemoprevention agent. Immunohistochemistry staining of tissue samples from animal tumors was performed to examine the gene expression.


RESULTS
Cells exposed to cactus pear extracts had a significant increase in apoptosis and growth inhibition in both immortalized epithelial cells and cancer cells in a dose- and time-dependent manner. It also affected cell cycle of cancer cells by increasing G1 and decreasing G2 and S phases. Both 4-HPR and cactus pear extracts significantly suppressed tumor growth in nude mice, increased annexin IV expression, and decreased VEGF expression.


CONCLUSIONS
Arizona cactus pear extracts effectively inhibited cell growth in several different immortalized and cancer cell cultures, suppressed tumor growth in nude mice, and modulated expression of tumor-related genes. These effects were comparable with those caused by a synthetic retinoid currently used in chemoprevention trials. The mechanism of the anti-cancer effects of cactus pear extracts needs to be further studied.
Zou
Da-ming
DM
Department of Obstetrics and Gynecology, Arizona Health Sciences Center, University of Arizona, Tucson, Arizona 85724, USA. dmzou@hotmail.com
Brewer
Molly
M
Garcia
Francisco
F
Feugang
Jean M
JM
Wang
Jian
J
Zang
Roungyu
R
Liu
Huaguang
H
Zou
Changping
C
D000818:Animals; D017314:Annexin A4 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D029421:Cactaceae / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000187:drug effects; D018890:Chemoprevention; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005638:Fruit / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000473:pathology; D010053:Ovary / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D017314:Annexin A4; D010936:Plant Extracts; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A