(±)-Gossypol induces apoptosis and autophagy in head and neck carcinoma cell lines and inhibits the growth of transplanted salivary gland cancer cells in BALB/c mice.
Racemic Gossypol [(±)-GOS], composed of both (-)-GOS and (+)-GOS, is a small BH3-mimetic polyphenol derived from cotton seeds. (±)-GOS has been employed and well tolerated by cancer patients. Head and neck carcinoma (HNC) represents one of the most fatal cancers worldwide, and a significant proportion of HNC expresses high levels of antiapoptotic Bcl-2 proteins. In this study, we demonstrate that (±)-GOS inhibits cell proliferation and induces apoptosis and autophagy of human pharynx, tongue, and salivary gland cancer cell lines and of mouse salivary gland cancer cells (SALTO). (±)-GOS was able to: (a) decrease the ErbB2 protein expression; (b) inhibit the phosphorylation of ERK1/2 and AKT; (c) stimulate p38 and JNK1/2 protein phosphorylation. (±)-GOS administration was safe in BALB/c mice and it reduced the growth of transplanted SALTO cells in vivo and prolonged mice median survival. Our results suggest the potential role of (±)-GOS as an antitumor agent in HNC patients.
a Department of Clinical Sciences and Translational Medicine, Faculty of Medicine , University of Rome "Tor Vergata" , Rome , Italy.
Monica
M
Benvenuto
a Department of Clinical Sciences and Translational Medicine, Faculty of Medicine , University of Rome "Tor Vergata" , Rome , Italy.
Rosanna
R
Mattera
b Department of Experimental Medicine , "Sapienza Università di Roma" , Rome , Italy.
Laura
L
Masuelli
a Department of Clinical Sciences and Translational Medicine, Faculty of Medicine , University of Rome "Tor Vergata" , Rome , Italy.
Gloria
G
Taffera
a Department of Clinical Sciences and Translational Medicine, Faculty of Medicine , University of Rome "Tor Vergata" , Rome , Italy.
Orlando
O
Andracchio
a Department of Clinical Sciences and Translational Medicine, Faculty of Medicine , University of Rome "Tor Vergata" , Rome , Italy.
Ilaria
I
Tresoldi
c Internal Medicine Residency Program , University of Rome "Tor Vergata" , Rome , Italy.
Paolo
P
Lido
a Department of Clinical Sciences and Translational Medicine, Faculty of Medicine , University of Rome "Tor Vergata" , Rome , Italy.
Maria Gabriella
MG
Giganti
d Department of Biomedical and Biotechnological Sciences , University of Catania , Catania , Italy.
Justyna
J
Godos
a Department of Clinical Sciences and Translational Medicine, Faculty of Medicine , University of Rome "Tor Vergata" , Rome , Italy.
Andrea
A
Modesti
a Department of Clinical Sciences and Translational Medicine, Faculty of Medicine , University of Rome "Tor Vergata" , Rome , Italy.
Roberto
R
Bei
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation; D018734:Genes, erbB-2; D006072:Gossypol / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse; D006072:Gossypol
(±)-Gossypol; BALB/c mice; BH3-mimetic compound; Head and neck cancer; autophagy