Sangivamycin induces apoptosis by suppressing Erk signaling in primary effusion lymphoma cells.

[primary effusion lymphoma]

Sangivamycin , a structural analog of adenosine and antibiotic exhibiting antitumor and antivirus activities , inhibits protein kinase C and the synthesis of both DNA and RNA . Primary effusion lymphoma (PEL ) is an aggressive neoplasm caused by Kaposi 's sarcoma -associated herpesvirus (KSHV ) in immunosuppressed patients and HIV-infected homosexual males . PEL cells are derived from post-germinal center B cells , and are infected with KSHV . Herein , we asked if sangivamycin might be useful to treat PEL . We found that sangivamycin killed PEL cells , and we explored the underlying mechanism . Sangivamycin treatment drastically decreased the viability of PEL cell lines compared to KSHV-uninfected B lymphoma cell lines . Sangivamycin induced the apoptosis of PEL cells by activating caspase-7 and -9 . Further , sangivamycin suppressed the phosphorylation of Erk 1 /2 and Akt , thus inhibiting activation of the proteins . Inhibitors of Akt and MEK suppressed the proliferation of PEL cells compared to KSHV-uninfected cells . It is known that activation of Erk and Akt signaling inhibits apoptosis and promotes proliferation in PEL cells . Our data therefore suggest that sangivamycin induces apoptosis by inhibiting Erk and Akt signaling in such cells . We next investigated whether sangivamycin , in combination with an HSP 90 inhibitor geldanamycin (GA ) or valproate (valproic acid ), potentiated the cytotoxic effects of the latter drugs on PEL cells . Compared to treatment with GA or valproate alone , the addition of sangivamycin enhanced cytotoxic activity . Our data thus indicate that sangivamycin may find clinical utility as a novel anti-cancer agent targeting PEL .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated