Octreotide induces caspase activation and apoptosis in human hepatoma HepG2 cells.
OBJECTIVE
To investigate the role of octreotide on cellular proliferation and apoptosis of human hepatoma (HepG2) cells.


METHODS
We studied cellular proliferation, apoptosis and the possible internal caspase-mediated apoptosis pathway involved, after treatment of HepG2 carcinoma cells with octreotide in comparison with the apoptosis caused by tumor necrosis factor-α (TNF-α). Activities of caspase-3, caspase-9, caspase-8 and caspase-2 were studied, while apoptosis was investigated through detection of DNA fragmentation and through identification of apoptotic cells with the annexin-V/propidium iodide flow cytometric method.


RESULTS
After an initial increase in HepG2 cellular proliferation, a significant inhibition was observed with 10⁻⁸ mol/L octreotide, while TNF-α dose-dependently decreased proliferation. Early and late apoptosis was significantly increased with both substances. Octreotide significantly increased caspase-3, caspase-8 and caspase-2 activity. TNF-α significantly increased only caspase-2. Cellular proliferation was decreased after treatment with octreotide or TNF-α alone but, in contrast to TNF-α, octreotide decreased proliferation only at concentrations of 10⁻⁸ mol/L, while lower concentrations increased proliferation.


CONCLUSIONS
Our findings are suggestive of caspase-mediated signaling pathways of octreotide antitumor activity in HepG2 cells, and indicate that measurements of serum octreotide levels may be important, at least in clinical trials, to verify optimal therapeutic drug concentrations.
Liver Research Laboratory, School of Medicine, University of Crete, Heraklion 71003, Greece.
Nikos J
NJ
Tsagarakis
Ioannis
I
Drygiannakis
Antonis G
AG
Batistakis
George
G
Kolios
Elias A
EA
Kouroumalis
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053143:Caspase 2 / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D015282:Octreotide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D053143:Caspase 2; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D015282:Octreotide
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