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Morinda citrifolia (Noni) Juice Augments Mammary Gland Differentiation and Reduces Mammary Tumor Growth in Mice Expressing the Unactivated c-erbB2 Transgene.

Clafshenkel WP, King TL, Kotlarczyk MP, Cline JM, Foster WG, Davis VL, Witt-Enderby PA - Evid Based Complement Alternat Med (2012)

Bottom Line: Mammary tumor latency, incidence, multiplicity, and metastatic incidence were unaffected by TNJ treatment, which suggests that it would not increase or decrease breast cancer risk in women taking TNJ for its other benefits.However, noni may be useful to enhance treatment responses in women with existing HER2/neu breast cancer since TNJ resulted in significant reductions in tumor weight and volume and in longer tumor doubling times in mice.A 30-day treatment with TNJ also induced significant changes in mammary secondary ductule branching and lobuloalveolar development, serum progesterone levels, and estrous cycling.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.

ABSTRACT
Morinda citrifolia (noni) is reported to have many beneficial properties, including on immune, inflammatory, quality of life, and cancer endpoints, but little is known about its ability to prevent or treat breast cancer. To test its anticancer potential, the effects of Tahitian Noni Juice (TNJ) on mammary carcinogenesis were examined in MMTV-neu transgenic mice. Mammary tumor latency, incidence, multiplicity, and metastatic incidence were unaffected by TNJ treatment, which suggests that it would not increase or decrease breast cancer risk in women taking TNJ for its other benefits. However, noni may be useful to enhance treatment responses in women with existing HER2/neu breast cancer since TNJ resulted in significant reductions in tumor weight and volume and in longer tumor doubling times in mice. Remarkably, its ability to inhibit the growth of this aggressive form of cancer occurred with the mouse equivalent of a recommended dose for humans (<3 oz/day). A 30-day treatment with TNJ also induced significant changes in mammary secondary ductule branching and lobuloalveolar development, serum progesterone levels, and estrous cycling. Additional studies investigating TNJ-induced tumor growth suppression and modified reproductive responses are needed to characterize its potential as a CAM therapy for women with and without HER2(+) breast cancer.

No MeSH data available.


Related in: MedlinePlus

Slower tumor growth kinetics in live animals was observed in the 10% TNJ-treated MMTV-neu animals than in the control group for large tumors. (a) Growth of spontaneously developed mammary tumors was measured weekly with calipers on 2 dimensions. The first solid tumor that was detected ≤5 mm in diameter in animals for the control (n = 9) and 10% TNJ (n = 13) groups was compared. These curves were significantly different, P < 0.0001, as determined by nonlinear regression analysis in Graphpad Prism 5. Due to the inherent heterogeneity of tumor behavior in this model related to the unique mutations that induce the mammary cancer [35], very rapidly and slowly growing tumors were excluded. The criteria for exclusion included tumors that grew for less than 2 months (9 weeks) since detection or did not reach a maximum volume of 900 mm3 by 12 weeks after detection. (b) Doubling time for solid mammary tumors with initial volume ≥532 mm3 and that grew to the maximum volume of ≥1765 mm3 with at least 2 weeks between these 2 measurements was used to assess the growth of tumors in the small range. The number of mice examined is shown in the bars for each group. (c) For intermediate size tumors, the doubling time for tumors growing for 2 weeks or longer within the volume range of 1765–3500 mm3 is shown with the number of mice per groups shown in the bars. (d) 10% TNJ increased mammary tumor doubling time for the large volume range (P = 0.036; 2500–4000 mm3). Only 3 tumors in the control group met the criteria of 2 weeks between the volumes for this range due to the rapid growth of their larger tumors. For this figure, only mice with noncystic mammary tumors that remained separate to allow accurate measurement were included. Mean ± SEM; TNJ: Tahitian Noni Juice; *indicates significance, P < 0.05 as determined by Mann-Whitney test.
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fig2: Slower tumor growth kinetics in live animals was observed in the 10% TNJ-treated MMTV-neu animals than in the control group for large tumors. (a) Growth of spontaneously developed mammary tumors was measured weekly with calipers on 2 dimensions. The first solid tumor that was detected ≤5 mm in diameter in animals for the control (n = 9) and 10% TNJ (n = 13) groups was compared. These curves were significantly different, P < 0.0001, as determined by nonlinear regression analysis in Graphpad Prism 5. Due to the inherent heterogeneity of tumor behavior in this model related to the unique mutations that induce the mammary cancer [35], very rapidly and slowly growing tumors were excluded. The criteria for exclusion included tumors that grew for less than 2 months (9 weeks) since detection or did not reach a maximum volume of 900 mm3 by 12 weeks after detection. (b) Doubling time for solid mammary tumors with initial volume ≥532 mm3 and that grew to the maximum volume of ≥1765 mm3 with at least 2 weeks between these 2 measurements was used to assess the growth of tumors in the small range. The number of mice examined is shown in the bars for each group. (c) For intermediate size tumors, the doubling time for tumors growing for 2 weeks or longer within the volume range of 1765–3500 mm3 is shown with the number of mice per groups shown in the bars. (d) 10% TNJ increased mammary tumor doubling time for the large volume range (P = 0.036; 2500–4000 mm3). Only 3 tumors in the control group met the criteria of 2 weeks between the volumes for this range due to the rapid growth of their larger tumors. For this figure, only mice with noncystic mammary tumors that remained separate to allow accurate measurement were included. Mean ± SEM; TNJ: Tahitian Noni Juice; *indicates significance, P < 0.05 as determined by Mann-Whitney test.

Mentions: Although the final tumor weight and volume indicate growth suppression, these measurements do not indicate how the size changed with time in the live animal; therefore, weekly growth patterns and doubling time were compared between the control and TNJ groups. Weekly growth profiles for control and TNJ-treated mammary tumors show significant size reduction with noni treatment (Figure 2(a)). Separation of the curves occurs around 9 weeks after tumor detection when the average volume of the control tumors is approximately 2500 mm3, suggesting that inhibition of tumor growth by TNJ compared to the control group occurs as the tumor volume increases. Therefore, tumor doubling time was determined on specific ranges of tumor volumes between 523 and 4000 mm3 (approximately 10 × 10 mm to 20 × 20 mm); these initial and final sizes correlate to clinically detectable tumor sizes of 1 cm and 2 cm which are associated with stage 1 breast cancer. Doubling time for several volume ranges was analyzed for small (523–1765 mm3, 10 × 10 mm to 15 × 15 mm), intermediate (1765–3500 mm3, 15 × 15 mm to 19 × 19 mm), and large tumor sizes (2500–4000 mm3, 17 × 17 mm to 20 × 20 mm) in mice (Figures 2(b)–2(d). TNJ treatment had significant growth inhibitory effects within the large volume range of 2500–4000 mm3 (Figure 2(d)), which corresponds to the size of tumors when the growth curves for the control and TNJ diverge (Figure 2(a)). Tumor doubling times for the entire size range approached significance for reduced tumor growth with TNJ treatment (523–4000 mm3, n = 9 and 17, P = 0.067; data not shown). These results suggest that TNJ treatment results in significant growth inhibitory effects, which likely account for the significant reductions in mammary tumor weight and volume at necropsy noted with chronic TNJ treatment (Figures 1(b) and 1(c)).


Morinda citrifolia (Noni) Juice Augments Mammary Gland Differentiation and Reduces Mammary Tumor Growth in Mice Expressing the Unactivated c-erbB2 Transgene.

Clafshenkel WP, King TL, Kotlarczyk MP, Cline JM, Foster WG, Davis VL, Witt-Enderby PA - Evid Based Complement Alternat Med (2012)

Slower tumor growth kinetics in live animals was observed in the 10% TNJ-treated MMTV-neu animals than in the control group for large tumors. (a) Growth of spontaneously developed mammary tumors was measured weekly with calipers on 2 dimensions. The first solid tumor that was detected ≤5 mm in diameter in animals for the control (n = 9) and 10% TNJ (n = 13) groups was compared. These curves were significantly different, P < 0.0001, as determined by nonlinear regression analysis in Graphpad Prism 5. Due to the inherent heterogeneity of tumor behavior in this model related to the unique mutations that induce the mammary cancer [35], very rapidly and slowly growing tumors were excluded. The criteria for exclusion included tumors that grew for less than 2 months (9 weeks) since detection or did not reach a maximum volume of 900 mm3 by 12 weeks after detection. (b) Doubling time for solid mammary tumors with initial volume ≥532 mm3 and that grew to the maximum volume of ≥1765 mm3 with at least 2 weeks between these 2 measurements was used to assess the growth of tumors in the small range. The number of mice examined is shown in the bars for each group. (c) For intermediate size tumors, the doubling time for tumors growing for 2 weeks or longer within the volume range of 1765–3500 mm3 is shown with the number of mice per groups shown in the bars. (d) 10% TNJ increased mammary tumor doubling time for the large volume range (P = 0.036; 2500–4000 mm3). Only 3 tumors in the control group met the criteria of 2 weeks between the volumes for this range due to the rapid growth of their larger tumors. For this figure, only mice with noncystic mammary tumors that remained separate to allow accurate measurement were included. Mean ± SEM; TNJ: Tahitian Noni Juice; *indicates significance, P < 0.05 as determined by Mann-Whitney test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: Slower tumor growth kinetics in live animals was observed in the 10% TNJ-treated MMTV-neu animals than in the control group for large tumors. (a) Growth of spontaneously developed mammary tumors was measured weekly with calipers on 2 dimensions. The first solid tumor that was detected ≤5 mm in diameter in animals for the control (n = 9) and 10% TNJ (n = 13) groups was compared. These curves were significantly different, P < 0.0001, as determined by nonlinear regression analysis in Graphpad Prism 5. Due to the inherent heterogeneity of tumor behavior in this model related to the unique mutations that induce the mammary cancer [35], very rapidly and slowly growing tumors were excluded. The criteria for exclusion included tumors that grew for less than 2 months (9 weeks) since detection or did not reach a maximum volume of 900 mm3 by 12 weeks after detection. (b) Doubling time for solid mammary tumors with initial volume ≥532 mm3 and that grew to the maximum volume of ≥1765 mm3 with at least 2 weeks between these 2 measurements was used to assess the growth of tumors in the small range. The number of mice examined is shown in the bars for each group. (c) For intermediate size tumors, the doubling time for tumors growing for 2 weeks or longer within the volume range of 1765–3500 mm3 is shown with the number of mice per groups shown in the bars. (d) 10% TNJ increased mammary tumor doubling time for the large volume range (P = 0.036; 2500–4000 mm3). Only 3 tumors in the control group met the criteria of 2 weeks between the volumes for this range due to the rapid growth of their larger tumors. For this figure, only mice with noncystic mammary tumors that remained separate to allow accurate measurement were included. Mean ± SEM; TNJ: Tahitian Noni Juice; *indicates significance, P < 0.05 as determined by Mann-Whitney test.
Mentions: Although the final tumor weight and volume indicate growth suppression, these measurements do not indicate how the size changed with time in the live animal; therefore, weekly growth patterns and doubling time were compared between the control and TNJ groups. Weekly growth profiles for control and TNJ-treated mammary tumors show significant size reduction with noni treatment (Figure 2(a)). Separation of the curves occurs around 9 weeks after tumor detection when the average volume of the control tumors is approximately 2500 mm3, suggesting that inhibition of tumor growth by TNJ compared to the control group occurs as the tumor volume increases. Therefore, tumor doubling time was determined on specific ranges of tumor volumes between 523 and 4000 mm3 (approximately 10 × 10 mm to 20 × 20 mm); these initial and final sizes correlate to clinically detectable tumor sizes of 1 cm and 2 cm which are associated with stage 1 breast cancer. Doubling time for several volume ranges was analyzed for small (523–1765 mm3, 10 × 10 mm to 15 × 15 mm), intermediate (1765–3500 mm3, 15 × 15 mm to 19 × 19 mm), and large tumor sizes (2500–4000 mm3, 17 × 17 mm to 20 × 20 mm) in mice (Figures 2(b)–2(d). TNJ treatment had significant growth inhibitory effects within the large volume range of 2500–4000 mm3 (Figure 2(d)), which corresponds to the size of tumors when the growth curves for the control and TNJ diverge (Figure 2(a)). Tumor doubling times for the entire size range approached significance for reduced tumor growth with TNJ treatment (523–4000 mm3, n = 9 and 17, P = 0.067; data not shown). These results suggest that TNJ treatment results in significant growth inhibitory effects, which likely account for the significant reductions in mammary tumor weight and volume at necropsy noted with chronic TNJ treatment (Figures 1(b) and 1(c)).

Bottom Line: Mammary tumor latency, incidence, multiplicity, and metastatic incidence were unaffected by TNJ treatment, which suggests that it would not increase or decrease breast cancer risk in women taking TNJ for its other benefits.However, noni may be useful to enhance treatment responses in women with existing HER2/neu breast cancer since TNJ resulted in significant reductions in tumor weight and volume and in longer tumor doubling times in mice.A 30-day treatment with TNJ also induced significant changes in mammary secondary ductule branching and lobuloalveolar development, serum progesterone levels, and estrous cycling.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.

ABSTRACT
Morinda citrifolia (noni) is reported to have many beneficial properties, including on immune, inflammatory, quality of life, and cancer endpoints, but little is known about its ability to prevent or treat breast cancer. To test its anticancer potential, the effects of Tahitian Noni Juice (TNJ) on mammary carcinogenesis were examined in MMTV-neu transgenic mice. Mammary tumor latency, incidence, multiplicity, and metastatic incidence were unaffected by TNJ treatment, which suggests that it would not increase or decrease breast cancer risk in women taking TNJ for its other benefits. However, noni may be useful to enhance treatment responses in women with existing HER2/neu breast cancer since TNJ resulted in significant reductions in tumor weight and volume and in longer tumor doubling times in mice. Remarkably, its ability to inhibit the growth of this aggressive form of cancer occurred with the mouse equivalent of a recommended dose for humans (<3 oz/day). A 30-day treatment with TNJ also induced significant changes in mammary secondary ductule branching and lobuloalveolar development, serum progesterone levels, and estrous cycling. Additional studies investigating TNJ-induced tumor growth suppression and modified reproductive responses are needed to characterize its potential as a CAM therapy for women with and without HER2(+) breast cancer.

No MeSH data available.


Related in: MedlinePlus