1. Academic Validation
  2. Momordicine-I, a Bitter Melon Bioactive Metabolite, Displays Anti-Tumor Activity in Head and Neck Cancer Involving c-Met and Downstream Signaling

Momordicine-I, a Bitter Melon Bioactive Metabolite, Displays Anti-Tumor Activity in Head and Neck Cancer Involving c-Met and Downstream Signaling

  • Cancers (Basel). 2021 Mar 21;13(6):1432. doi: 10.3390/cancers13061432.
Subhayan Sur 1 Robert Steele 1 T Scott Isbell 1 Kalyan Nagulapalli Venkata 2 Mostafa E Rateb 3 Ratna B Ray 1 4
Affiliations

Affiliations

  • 1 Department of Pathology, Saint Louis University, St. Louis, MO 63104, USA.
  • 2 Department of Pharmaceutical and Administrative Sciences, Saint Louis College of Pharmacy, St. Louis, MO 63104, USA.
  • 3 School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, Scotland, UK.
  • 4 Cancer Center, Saint Louis University, St. Louis, MO 63104, USA.
Abstract

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.

Keywords

C-MET signaling; bitter melon (Momordica charantia); head and neck cancer; momordicine-I; therapy.

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