Approximately 41% of women are utilizing complementary and alternative medicine (CAM) forms of medicine to manage their breast cancer [1
], including products from the Morinda citrifolia
(noni) plant. An edible and medicinal tropical plant, Morinda citrifolia,
has been used for over 2000 years by Polynesian cultures as an herbal remedy for infection, arthritis, diabetes, asthma, hypertension, and pain [3
]. All parts of the plant including the roots, bark, stems, flowers, leaves, and fruit are components in various combinations of 40 known and recorded herbal remedies [3
], with the fruit being the most researched [4
]. The popularity of noni has spread from Polynesian and Hawaiian cultures with its global introduction in the early 1990s [5
], and its products are now readily available in health food stores and on the Internet.
Several studies reported that noni has multiple cancer protective properties. Oncostatic activities related to cancer prevention include reductions in TPA- or EGF-induced cell transformation [6
], reduction in DMBA-induced DNA damage and lesion formation [7
], and concentration-dependent free-radical scavenging effects [8
]. Similarly, additional anticancer activities, including antiangiogenic [11
] and cancer cell-selective cytotoxic properties [12
], suggest its potential as a treatment to inhibit tumor growth and progression. Although only a few studies have tested the cancer inhibitory actions of noni in vivo
, one recent study demonstrated that noni fruit powder had both preventative and treatment efficacy on rat esophageal cancer induced by N-nitrosomethylbenzylamine [14
]. For breast cancer, although its oncostatic properties suggest that noni would inhibit carcinogenesis, there have been no preclinical studies testing its potential to influence mammary tumor development, except for an abstract reporting that noni inhibits the initiation stage of DMBA-induced mammary cancer in rats [7
]. Moreover, women are utilizing noni for the prevention and treatment of breast cancer and as a secondary course of treatment following conventional chemotherapy [15
], even though its ability to influence breast cancer development or progression has not been determined. Therefore, in the present study, the impact of noni fruit juice administration on mammary tumor development and tumor growth was investigated in MMTV-neu
transgenic mice. This model expresses the unactivated rat neu
B2) gene under the transcriptional control of the mouse mammary tumor virus (MMTV) promoter. This mouse model mimics many features of HER2/neu+
breast cancer, including stochastic tumor onset, focal tumors arising near hyperplastic tissue, a long latency period, estrogen-dependent tumor development, and metastatic progression to the lungs [16
]. As no studies have investigated the influence of noni on metastatic progression in any type of cancer, this study with MMTV-neu
mice will examine its ability to influence the spread of cancer outside the mammary gland.
Seven case reports of liver damage have been reported between 2005 and 2011 associated with noni use alone or in combination with other CAM or traditional medications [19
]. Since noni is a common herbal therapy with sales in U.S.A estimated over $250 million in 2005 [4
], these few reports suggest that hepatotoxicity is a rare event. In addition, preclinical studies suggest that noni therapies may have hepatoprotective properties [23
]. Concerns with kidney function have also arisen due to a case report documenting elevated potassium levels in a patient with chronic renal insufficiency taking noni juice [25
]. Therefore, to determine if long-term administration of a recommended dose (equivalent to less than 3
ounces/day in humans) shows any liver or kidney toxicity, serum markers and histopathology were examined in aged mice chronically treated with noni juice.
In this study, the influence of a noni fruit juice, Tahitian Noni juice (TNJ), on mammary tumor development, growth, and metastatic progression in the MMTV-neu mice was investigated. Additionally, to identify potential responses that could influence mammary tumorigenesis, differentiation in the normal mammary gland, serum hormone levels, and estrous cycling was examined in sexually mature female mice treated for 1 month, prior to tumor onset.