Dihydrosphingosine (DHSph, sphinganine)
Fumonisin B1 inhibits ceramide synthases, as well as induces increase in sphingosine kinases and palmityl transferase, elevating levels of DHSph, DHS1P.
Hepatocyte TNFa, IFNg, IL12 are also increased (Suzuki).
Fumonisin B1 inhibits ceramide synthases
Ceramide driven signaling cascades are involved in processes blocked by fumonisin:
- Apoptosis of:
- endothelial cells (Berdyshev)
- skeletal muscle myotubes (Turpin)
- ovocytes (Kalo)
- early postnatal oligodendrocytes (Novgorodov)
- myeloblasts, induced by retinoids (Jiang)
- Mutated p53 reactivation (Liu)
By interfering with the Ceramide pathway, Fumonisin blocks efficacy of many anticancer therapies. Chemotherapies(Cianchi); inhibition by Fumonisin of daunorubicin, retinoids, irinotecan (Senchenkov). Resistance to Radiotherapy of glioma and lymphoma cell lines (Michael)
This is linked to strong epidemiological data from China, South Africa and sub-Saharan Africa, comparing areas of low and high esophageal cancer incidence, with levels of maize-derived Fumonisin ingesta
Sphingosine -1 phosphate (S1P)
A body of evidence points towards Fumonisine B1 responsibility in esophageal cancers
Williams J.H. et al; Am J Clin Nutr 2010, 92: 154
In sub Saharian Africa deaths from esophageal cancer are strongly correlated with maize ingesta, whereas rice, manioc and peanuts ingesta are negatively correlated.
Hepatic cancer is correlated with rice ingesta (aflatoxins)
average daily dietary intake
Huantai townships are at low risk of hepatocarcinoma (HC) or esophageal cancer (EC)
Huaian townships are at high risk of ESOPHAGEAL cancer: high FB1 intake
Fusui townships are at high risk of hepatocarcinoma: high AFB1 intake
Sun G; et al; Food Addit. Contam.2011; 28: 461