Isothiocyanates (ITCs) are a class of naturally occurring compounds shown to have anti-cancer activities and promising chemopreventive prospects. Moringa oleifera (MO), a cruciferous vegetable widely cultivated in the tropics, has been used by locals to treat different diseases for centuries. Moringa Isothiocyanates (MIC) is produced from MO when the four unique sugar-modified aromatic glucosinolates it contains are hydrolyzed in a reaction catalyzed by myrosinase. In this study, we evaluated the efficacy of MIC on 9 different breast cancer cell lines and found it to be a potent anti-cancer agent. Interestingly, two of the most sensitive cells lines to MIC, BT474 and HCC1954, were both positive for HER2. HER2 is amplified in up to 30% of breast cancers and is positively correlated with poor prognosis in patients. We hypothesized that HER2 overexpression induces hypersensitivity to MIC in breast cancer cells. Our studies using MCF7 and MDA-MB-231 with and without HER2 overexpression further confirmed the correlation between HER2 overexpression and hypersensitivity to MIC. To understand why increased sensitivity to MIC was observed in HER2+ breast cancer cell lines as compared to HER2- cell lines, intracellular levels of reactive oxygen species (ROS) was examined. Higher basal intracellular ROS levels were observed in HER2+ cell lines compared to HER2- ones. We also hypothesized that the anti-cancer activity of MIC may involve an ROS regulatory pathway. Indeed, we found that MIC clearly regulates NRF2 and KEAP1 expression in multiple breast cancer cell lines. Additionally, MIC also triggers changes in intracellular ROS levels in a cell line-dependent manner, suggesting that MIC adopts different mechanisms of action in different breast cancer cell lines. Our work shows that MIC may open new frontiers in breast cancer prevention and therapy, particularly for those with HER2 amplification.
Subject (authority = RUETD)
Topic
Microbiology and Molecular Genetics
Subject (authority = ETD-LCSH)
Topic
Moringa oleifera
Subject (authority = ETD-LCSH)
Topic
Breast--Cancer
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8867
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xii, 87 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Julia Bolanle Olayanju
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
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