Breast cancer is the most prevalent cancer among women in the United States. DNA damage induced by chemical exposure and oxidative stress, as well as estrogenic regulation of mammary gland differentiation and tumor growth are among the critical factors affecting the incidence and development of breast cancer. Research carried out in the laboratory of the principal investigator focused on the anti-breast cancer function of an ethanol/water extract from bamboo Phyllostachys edulis, one of the most widely distributed and fastest growing plants in the world. The preliminary studies revealed that bamboo extract (BEX) contained a high level of flavonoids, and significantly enhanced the resistance of mammalian cells to varied oxidative stresses. BEX as a dietary supplement (0.5%, w/w) delayed the onset of palpable mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley (SD) rats, decreased the tumor incidence by 44%, and dramatically reduced tumor multiplicity. BEX supplementation also enhanced the activity of sulfotransferases (SULT) in the liver, an enzyme family that conjugates estrogens. The preliminary results indicate that BEX may affect the functions of multiple tissues that synergistically lead to the anti-breast cancer effect. This project will examine the hypothesis under two Specific Aims:
Aim 1. To investigate BEX- induced changes in mammary tumors. Magnetic Resonance Imaging (MRI) techniques will be employed in this study to closely monitor the starting time and accurately measure the growth rate of the micro-tumors in the mammary glands before they would be perceptible by the regular palpation method;thereby efficiently evaluating the inhibitory effects of BEX on the initiation and early-stage promotion of the mammary tumor. The gene expression of key factors in cellular proliferation and apoptosis pathways, and oxidative stress damage on DNA and proteins in the tumor tissues will be assessed at different developmental stages to reveal BEX- induced changes on the molecular levels.
Aim 2. To investigate BEX-induced changes in both mammary glands and the liver that favor breast cancer prevention. These include: (i) Inhibition on the carcinogenic effects of DMBA through: (a) regulation of the metabolism of DMBA in the liver and mammary tissues, and (b) amelioration of DMBA-induced oxidative stress in the mammary glands. (ii) Enhancement of estrogen metabolism through up-regulation of SULT activity in the liver. (iii) Acceleration of mammary gland differentiation through its potential phytoestrogenic activity. Successful performance of this project will direct more focused research into the cellular and molecular pathways, the major target tissues, and the critical time periods through which BEX exerts the anti-breast cancer function. This will lay a firm basis for the principal investigator to achieve the long-term goal of characterizing the potentially novel anti-breast cancer compound(s) in BEX, improving the efficiency of the product, and eventually applying this abundant, easily available and sustainable natural resource in the chemoprevention of breast cancer in human subjects.

Public Health Relevance

This project aims to explore the anti-breast cancer function of an ethanol/water extract from bamboo Phyllostachys edulis. Knowledge obtained from these studies will guide the application of this abundant and sustainable natural resource in chemoprevention of breast cancer, the most prevalent cancer among women in the United States.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AT005139-02
Application #
7924797
Study Section
Special Emphasis Panel (ZAT1-PK (02))
Program Officer
Alekel, D Lee
Project Start
2009-09-01
Project End
2013-08-31
Budget Start
2010-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$227,948
Indirect Cost
Name
University of Hawaii
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Pang, Xiaosha; Panee, Jun (2016) Anti-inflammatory Function of Phyllostachys Edulis Extract in the Hippocampus of HIV-1 Transgenic Rats. J HIV AIDS 2:
Panee, Jun (2015) Potential Medicinal Application and Toxicity Evaluation of Extracts from Bamboo Plants. J Med Plant Res 9:681-692
Pang, Xiaosha; Panee, Jun (2014) Roles of glutathione in antioxidant defense, inflammation, and neuron differentiation in the thalamus of HIV-1 transgenic rats. J Neuroimmune Pharmacol 9:413-23
Del Rosario, Adeline; McDermott, Mindy M; Panee, Jun (2012) Effects of a high-fat diet and bamboo extract supplement on anxiety- and depression-like neurobehaviours in mice. Br J Nutr 108:1143-9
Higa, Jason K; Liang, Zhibin; Williams, Philip G et al. (2012) Phyllostachys edulis compounds inhibit palmitic acid-induced monocyte chemoattractant protein 1 (MCP-1) production. PLoS One 7:e45082
Panee, Jun (2012) Monocyte Chemoattractant Protein 1 (MCP-1) in obesity and diabetes. Cytokine 60:1-12
Higa, Jason K; Liu, Wanyu; Berry, Marla J et al. (2011) Supplement of bamboo extract lowers serum monocyte chemoattractant protein-1 concentration in mice fed a diet containing a high level of saturated fat. Br J Nutr 106:1810-3
Koide, Cheryl L K; Collier, Abby C; Berry, Marla J et al. (2011) The effect of bamboo extract on hepatic biotransforming enzymes--findings from an obese-diabetic mouse model. J Ethnopharmacol 133:37-45
Higa, Jason K; Panee, Jun (2011) Bamboo extract reduces interleukin 6 (IL-6) overproduction under lipotoxic conditions through inhibiting the activation of NF-?B and AP-1 pathways. Cytokine 55:18-23