Momordicine-I, a Bitter Melon Bioactive Metabolite, Displays Anti-Tumor Activity in Head and Neck Cancer Involving c-Met and Downstream Signaling.
Subhayan SurRobert SteeleT Scott IsbellKalyan Nagulapalli VenkataMostafa E RatebRatna B RayPublished in: Cancers (2021)
Head and neck cancer (HNC) is one of the most aggressive cancers, and treatments are quite challenging due to the difficulty in early diagnosis, lack of effective chemotherapeutic drugs, adverse side effects and therapy resistance. We identified momordicine-I (M-I), a bioactive secondary metabolite in bitter melon (Momordica charantia), by performing liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS) analysis. M-I inhibited human HNC cell (JHU022, JHU029, Cal27) viability in a dose-dependent manner without an apparent toxic effect on normal oral keratinocytes. Mechanistic studies showed that M-I inhibited c-Met and its downstream signaling molecules c-Myc, survivin, and cyclin D1 through the inactivation of STAT3 in HNC cells. We further observed that M-I was non-toxic and stable in mouse (male C57Bl/6) blood, and a favorable pharmacokinetics profile was observed after IP administration. M-I treatment reduced HNC xenograft tumor growth in nude mice and inhibited c-Met and downstream signaling. Thus, M-I has potential therapeutic implications against HNC.
Keyphrases
- mass spectrometry
- liquid chromatography
- high resolution
- tyrosine kinase
- high resolution mass spectrometry
- tandem mass spectrometry
- endothelial cells
- cell cycle arrest
- induced apoptosis
- simultaneous determination
- single cell
- magnetic resonance imaging
- emergency department
- gas chromatography
- cell death
- mesenchymal stem cells
- type diabetes
- cell proliferation
- oxidative stress
- skeletal muscle
- capillary electrophoresis
- magnetic resonance
- metabolic syndrome
- insulin resistance
- wound healing
- ms ms
- solid phase extraction
- drug induced