Analogs of Vitamin E Epitomized by alpha-Tocopheryl Succinate for Pancreatic Cancer Treatment In Vitro Results Induce Caution for In Vivo Applications

作者：Greco Eliana; Basso Daniela; Fadi Elisa; Padoan Andrea; Fogar Paola; Zambon Carlo Federico; Navaglia Filippo; Bozzato Dania; Moz Stefania; Pedrazzoli Sergio; Plebani Mario^*

来源：Pancreas, 2010, 39(5): 662-668.

DOI：10.1097/MPA.0b013e3181c8b48c

• pancreatic cancer
• alpha-tocopheryl succinate
• 5-fluorouracil
• Bax/Bak
• SMAD/DPC4
• CAPAN1
• BxPC3
• MIA PaCa2
• PSN1
• PANC1
• pancreatic cancer cell lines

Objectives: alpha-Tocopheryl succinate (alpha-TOS) is thought to be toxic only for cancer cells. We ascertained in vitro alpha-TOS effects on pancreatic cancer (PC) and normal cell growth and verified whether the combination of nontoxic alpha-TOS and 5-fluorouracil (5-FU) doses causes cancer cell death and whether alpha-TOS effects are mediated by the proapoptotic proteins Bax/Bak and/or SMAD4/DPC4 status.
Methods: Five PC cell lines, myoblasts, normal monocytes, wild-type (WT) and Bax/Bak double knockout mouse embryonic fibroblast (MEF) cells, and permanently SMAD4/DPC4-transfected PSN1 cells were cultured in 1% and 10% fetal calf serums (FCSs), without or with alpha-TOS (5-500 mu mol/L). Nontoxic 5-FU (0.0001 mmol/L) and alpha-TOS alone or in combination were also evaluated.
Results: Only PSN1 PC cell line, which had SMAD4/DPC4 homozygous deletion, was sensitive to nontoxic alpha-TOS doses (5 mu mol/L in 1% FCS and 50 mu mol/L in 10% FCS). A 20-mu mol/L alpha-TOS inhibited MEF-WT, not MEF-double knockout growth. Only PSN1 cells were sensitive to nontoxic 5-FU and alpha-TOS combination. SMAD4/DPC4 transfection restored PSN1 resistance to the effects of combined 5-FU and alpha-TOS effects.
Conclusions: Only a minority of PC cells are sensitive to the anti-proliferative effects of alpha-TOS, any sensitivity appearing to be correlated with SMAD4/DPC4 homozygous deletion and Bax/Bak expression.

• 出版日期2010-7