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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

Thirty-day treatment of virgin, tumor-free MMTV-neu mice with 10% TNJ results in morphological differences in mammary gland differentiation. Representative photomicrographs shown for 2 animals in the control (panels a–d) and 10% TNJ-treated (panels e–h) groups; animal 1 is shown in panels (a) and (b) for control and (e) and (f) for TNJ groups and animal 2 is shown in panels (c) and (d) for control and (g) and (h) for TNJ groups. For panels (a) and (e) images were captured at the terminus of the gland at magnification 13x; panels (b) and (f) show enlargement of the area outlined by the dashed box at magnification 26x. For panels (c) and (g), images depict the area around the inguinal lymph node to qualitatively assess the degree of ductal branching and lobular differentiation at magnification 13x; panels (d) and (h) are the magnified portion of the gland in the adjacent micrograph outlined by the dashed boxes, magnification 26x. Black arrows identify lobular structures. Inset bars measure 1 mm. The graphs in panels (i) and (j) show quantification of the differentiation evident in the photomicrographs for the mice treated for 30 days with 10% TNJ. (i) The number of secondary ducts was quantified by locating larger, distinct primary ducts and counting the number of secondary branches along a 1-mm distance. Secondary ductule branching in the mammary glands of virgin, tumor-free MMTV-neu mice is significantly increased, P = 0.0001; control, n = 4, and TNJ, n = 5. (j) The average number of lobules was determined by quantifying lobuloalveolar structures in four separate 16 mm2 areas for each animal. The number of lobules was also significantly increased by TNJ in the same animals analyzed for secondary branching, P = 0.0015. Mean ± SEM are shown; TNJ: Tahitian Noni Juice; **indicates significance, P < 0.002; ***indicates significance, P = 0.0001 by Student's t-test.
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fig7: Thirty-day treatment of virgin, tumor-free MMTV-neu mice with 10% TNJ results in morphological differences in mammary gland differentiation. Representative photomicrographs shown for 2 animals in the control (panels a–d) and 10% TNJ-treated (panels e–h) groups; animal 1 is shown in panels (a) and (b) for control and (e) and (f) for TNJ groups and animal 2 is shown in panels (c) and (d) for control and (g) and (h) for TNJ groups. For panels (a) and (e) images were captured at the terminus of the gland at magnification 13x; panels (b) and (f) show enlargement of the area outlined by the dashed box at magnification 26x. For panels (c) and (g), images depict the area around the inguinal lymph node to qualitatively assess the degree of ductal branching and lobular differentiation at magnification 13x; panels (d) and (h) are the magnified portion of the gland in the adjacent micrograph outlined by the dashed boxes, magnification 26x. Black arrows identify lobular structures. Inset bars measure 1 mm. The graphs in panels (i) and (j) show quantification of the differentiation evident in the photomicrographs for the mice treated for 30 days with 10% TNJ. (i) The number of secondary ducts was quantified by locating larger, distinct primary ducts and counting the number of secondary branches along a 1-mm distance. Secondary ductule branching in the mammary glands of virgin, tumor-free MMTV-neu mice is significantly increased, P = 0.0001; control, n = 4, and TNJ, n = 5. (j) The average number of lobules was determined by quantifying lobuloalveolar structures in four separate 16 mm2 areas for each animal. The number of lobules was also significantly increased by TNJ in the same animals analyzed for secondary branching, P = 0.0015. Mean ± SEM are shown; TNJ: Tahitian Noni Juice; **indicates significance, P < 0.002; ***indicates significance, P = 0.0001 by Student's t-test.

Mentions: Ovarian hormones control morphological changes in breast architecture in both humans and rodents [38–40]. In mice, estrogen regulates the elongation of the primary mammary ducts into the mammary fat pad, while progesterone stimulates secondary and tertiary branching and lobuloalveolar development [40]. Qualitative assessment from whole mounts of the inguinal mammary glands of TNJ-treated mice showed a much higher degree of ductal branching and exhibited marked lobuloalveolar development (Figures 7(e)–7(h)) compared to the glands from the control mice (Figures 7(a)–7(d)). To quantify these specific parameters associated with progesterone actions, significantly more secondary ducts along a 1 mm length of the primary duct were detected in the TNJ-treated group compared to the control group (Figure 7(i)). Additionally, the average number of lobuloalveolar structures was significantly higher in the 10% TNJ-treated group (Figure 7(j)). Other analyzed parameters associated with estrogenic activity in the mammary gland, including the number of terminal end buds at the leading edge of the ductal tree, the average size of terminal end bud structures, and the average thickness of primary ducts, were not significantly different between the control and TNJ-treated animals (data not shown). Collectively, the observed responses induced by TNJ treatment (increased ductal arborization and lobule formation) correlate with known progesterone actions even with lower progesterone levels in MMTV-neu mice in estrus.


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)

Thirty-day treatment of virgin, tumor-free MMTV-neu mice with 10% TNJ results in morphological differences in mammary gland differentiation. Representative photomicrographs shown for 2 animals in the control (panels a–d) and 10% TNJ-treated (panels e–h) groups; animal 1 is shown in panels (a) and (b) for control and (e) and (f) for TNJ groups and animal 2 is shown in panels (c) and (d) for control and (g) and (h) for TNJ groups. For panels (a) and (e) images were captured at the terminus of the gland at magnification 13x; panels (b) and (f) show enlargement of the area outlined by the dashed box at magnification 26x. For panels (c) and (g), images depict the area around the inguinal lymph node to qualitatively assess the degree of ductal branching and lobular differentiation at magnification 13x; panels (d) and (h) are the magnified portion of the gland in the adjacent micrograph outlined by the dashed boxes, magnification 26x. Black arrows identify lobular structures. Inset bars measure 1 mm. The graphs in panels (i) and (j) show quantification of the differentiation evident in the photomicrographs for the mice treated for 30 days with 10% TNJ. (i) The number of secondary ducts was quantified by locating larger, distinct primary ducts and counting the number of secondary branches along a 1-mm distance. Secondary ductule branching in the mammary glands of virgin, tumor-free MMTV-neu mice is significantly increased, P = 0.0001; control, n = 4, and TNJ, n = 5. (j) The average number of lobules was determined by quantifying lobuloalveolar structures in four separate 16 mm2 areas for each animal. The number of lobules was also significantly increased by TNJ in the same animals analyzed for secondary branching, P = 0.0015. Mean ± SEM are shown; TNJ: Tahitian Noni Juice; **indicates significance, P < 0.002; ***indicates significance, P = 0.0001 by Student's t-test.
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Related In: Results  -  Collection

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fig7: Thirty-day treatment of virgin, tumor-free MMTV-neu mice with 10% TNJ results in morphological differences in mammary gland differentiation. Representative photomicrographs shown for 2 animals in the control (panels a–d) and 10% TNJ-treated (panels e–h) groups; animal 1 is shown in panels (a) and (b) for control and (e) and (f) for TNJ groups and animal 2 is shown in panels (c) and (d) for control and (g) and (h) for TNJ groups. For panels (a) and (e) images were captured at the terminus of the gland at magnification 13x; panels (b) and (f) show enlargement of the area outlined by the dashed box at magnification 26x. For panels (c) and (g), images depict the area around the inguinal lymph node to qualitatively assess the degree of ductal branching and lobular differentiation at magnification 13x; panels (d) and (h) are the magnified portion of the gland in the adjacent micrograph outlined by the dashed boxes, magnification 26x. Black arrows identify lobular structures. Inset bars measure 1 mm. The graphs in panels (i) and (j) show quantification of the differentiation evident in the photomicrographs for the mice treated for 30 days with 10% TNJ. (i) The number of secondary ducts was quantified by locating larger, distinct primary ducts and counting the number of secondary branches along a 1-mm distance. Secondary ductule branching in the mammary glands of virgin, tumor-free MMTV-neu mice is significantly increased, P = 0.0001; control, n = 4, and TNJ, n = 5. (j) The average number of lobules was determined by quantifying lobuloalveolar structures in four separate 16 mm2 areas for each animal. The number of lobules was also significantly increased by TNJ in the same animals analyzed for secondary branching, P = 0.0015. Mean ± SEM are shown; TNJ: Tahitian Noni Juice; **indicates significance, P < 0.002; ***indicates significance, P = 0.0001 by Student's t-test.
Mentions: Ovarian hormones control morphological changes in breast architecture in both humans and rodents [38–40]. In mice, estrogen regulates the elongation of the primary mammary ducts into the mammary fat pad, while progesterone stimulates secondary and tertiary branching and lobuloalveolar development [40]. Qualitative assessment from whole mounts of the inguinal mammary glands of TNJ-treated mice showed a much higher degree of ductal branching and exhibited marked lobuloalveolar development (Figures 7(e)–7(h)) compared to the glands from the control mice (Figures 7(a)–7(d)). To quantify these specific parameters associated with progesterone actions, significantly more secondary ducts along a 1 mm length of the primary duct were detected in the TNJ-treated group compared to the control group (Figure 7(i)). Additionally, the average number of lobuloalveolar structures was significantly higher in the 10% TNJ-treated group (Figure 7(j)). Other analyzed parameters associated with estrogenic activity in the mammary gland, including the number of terminal end buds at the leading edge of the ductal tree, the average size of terminal end bud structures, and the average thickness of primary ducts, were not significantly different between the control and TNJ-treated animals (data not shown). Collectively, the observed responses induced by TNJ treatment (increased ductal arborization and lobule formation) correlate with known progesterone actions even with lower progesterone levels in MMTV-neu mice in estrus.

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