An Evaluation of the Efficacy of Morinda citrifolia (Noni) on the Development and Progression of Breast Cancer in the MMTV-neu Mouse Model
School of Pharmacy
Morinda citrifolia, Noni, Tahitian Noni Juice, Breast cancer, Complementary and alternative medicine, MMTV-neu
Seventy-nine percent of individuals consuming Morinda citrifolia (Noni), a popular, over-the-counter dietary supplement, have reported beneficial effects (of 25, 000 testimonials). A recent addition to the list of activities synonymous with Noni juice consumption includes its potential to prevent the development of cancer in some models. However, there is no in vivo data that suggests its potential efficacy against the development of human breast tumors. Therefore, investigation into the potential use of Noni as an adjuvant therapy for the prevention and treatment of breast cancer is warranted and formed the basis of this study. The effects of Tahitian Noni® Juice (TNJ) on the development and progression of mammary tumorigenesis were studied in the MMTV-neu mouse model. Investigating the effects of TNJ in the MMTV-neu model has several benefits, including the spontaneous development of mammary tumors and its relation to breast cancers that over-express HER2. Investigation into the mechanistic activity of TNJ in normal mammary glands (pre-tumor study) revealed that a thirty day treatment with 10% TNJ has the potential to down-regulate enzymes implicated in local hormone biosynthesis as well as the transcribed message for epidermal growth factor. Concomitantly, there was a 5-fold increase in β-casein expression, a known marker of mammary gland differentiation, in the mammary glands of treated mice. Mammary gland whole mount assessments supported significant changes in mammary gland architecture, including increases in secondary ductule branching (p 0.0001) and alveolobular development (p = 0.0015). Thirty day treatment with TNJ was also capable of causing a significant reduction in circulating levels of progesterone (p = 0.0316) and reduced the number of estrous cycles of treated mice (p = 0.0102). To investigate whether tumor outcomes were also modified, the long-term effects of 10% TNJ administration were examined.
Mammary tumor latency, mammary tumor incidence, mammary tumor multiplicity, and metastatic incidence in the lungs were unaffected with 10% TNJ treatment compared to the control group. However, TNJ demonstrated potent growth inhibitory activity with significant reductions in mammary tumor weight and mammary tumor volume (p = 0.0074 and p = 0.0141, respectively), and a significant reduction in solid primary mammary tumor doubling time and growth rate for a specific window of tumor sizes (p = 0.0364 and p = 0.0427, respectively; 2500-4000 mm3). Finally, the long-term administration of TNJ did not result in hepato- and nephrotoxicity for the parameters analyzed in this study. The ability of TNJ to augment mammary gland differentiation may affect the perpetuation of events leading to continued tumor growth in the mammary tissue. Moreover, TNJ demonstrates the potential to reduce mammary tumor burden and growth rates in aggressive, hormone-independent cancers such as those over-expressing HER2. Ultimately, this may enhance the manageability and survivability of HER2 over-expressing breast cancer by allowing additional time for surgical or therapeutic intervention.
Clafshenkel, W. (2009). An Evaluation of the Efficacy of Morinda citrifolia (Noni) on the Development and Progression of Breast Cancer in the MMTV-neu Mouse Model (Master's thesis, Duquesne University). Retrieved from https://dsc.duq.edu/etd/1572