Moringa oleifera Lam. (M. oleifera), which belongs to the Moringaceae family, is a perennial deciduous tropical tree, and native to the south of the Himalayan Mountains in northern India. M. oleifera is rich in proteins, vitamin A, minerals, essential amino acids, antioxidants, and flavonoids, as well as isothiocyanates. The extracts from M. oleifera exhibit multiple nutraceutical or pharmacological functions including anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, neuroprotective, hypoglycemic, and blood lipid-reducing functions. The beneficial functions of M. oleifera are strongly associated with its phytochemicals such as flavonoids or isothiocyanates with bioactivity. In this review, we summarize the research progress related to the bioactivity and pharmacological mechanisms of M. oleifera in the prevention and treatment of a series of chronic diseases—including inflammatory diseases, neuro-dysfunctional diseases, diabetes, and cancers—which will provide a reference for its potential application in the prevention and treatment of chronic diseases or health promotion.

We recently discovered that the Warburg effect, defined by the dramatically enhanced metabolism of glucose to pyruvate, even in well-oxygenated cancer cells, can occur as a consequence of mutations that enhance lipid biosynthesis at the expense of respiratory capacity. Specifically, mutations in the E1 subunit of either of two respiratory enzymes, pyruvate dehydrogenase (PDC) or α-ketoglutarate dehydrogenase (KGDC), change substrate specificity from the 3-carbon α-ketoacid pyruvate, or the 5-carbon α-ketoacid α-ketoglutarate, to a 4-carbon α-ketoacid oxaloacetate (OADC). These mutations result in OADC-catalyzed synthesis of malonyl-CoA (MaCoA), the essential precursor of all fatty acids. These mutants arose as spontaneous suppressors of a yeast acc1cs cold-sensitive mutation encoding an altered form of AcCoA carboxylase (Acc1) that fails to produce MaCoA at the restrictive temperature (16°C). Notably, these suppressors are respiratory defective as a result of the same nuclear mutations that suppress acc1cs. These mutants also suppress sensitivity to Soraphen A, a potent inhibitor of Acc1 activity, at normal temperature (30°C). To our knowledge, OADC activity has never been identified in eukaryotic cells. Our results offer a novel perspective on the Warburg effect: the reprogramming of energy metabolism in cancer cells as a consequence of mutational impairment of respiration to meet the fatty acid requirements of rapidly proliferating cells. We suggest OADC activity is a common feature of cancer cells and represents a novel target for the development of chemotherapeutics.

Isothiocyanates (ITCs) are a class of natural products with promising anti-cancer activities and chemopreventive prospects. Moringa oleifera is a plant widely cultivated in the tropics and has been popularly used for centuries by locals to treat different diseases. Moringa leaves contain four unique sugar-modified aromatic glucosinolates, which can be converted to moringa isothiocyanates (MICs) by myrosinase also present in the leaves. In this study, we tested the efficacy of MIC-1 on 9 different breast cancer cell lines and found it to be a potent anti-cancer agent against them. Interestingly, the two cells lines most sensitive to MIC-1, BT474 and HCC1954, were both positive for HER2, which is amplified in up to 30% of breast cancer and correlates with poor prognosis. The correlation between HER2 overexpression and hypersensitivity to MIC was further confirmed using pairs of MCF-7 and MDA-MB-231 cells with and without HER2 overexpression. In studies to understand why the HER2+ breast cancer cells were more sensitive to MIC than HER2- lines, we observed higher basal intracellular ROS levels in HER2+ breast cancer cell lines compared to HER2- cells. Moreover, we observed that MIC regulates the abundance of KEAP1 and NRF2 across the different cell lines used in this study. In some cases, MIC-1 upregulated both KEAP1 and NRF2 at the same time, suggesting that it may directly or indirectly inactivate KEAP1 thereby stabilizing NRF2. More efforts are underway to elucidate the precise mechanisms of action. Our work shows that MICs may open new frontiers in breast cancer prevention and therapy, particularly for those with HER2 amplification. Citation Format: JULIA B. OLAYANJU, Bing Xia. HER2 overexpression induces sensitivity to moringa isothiocyanates in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-017.