Vitamin E in the management of pancreatic cancer: A scoping review

Table 1 In vitro studies investigating effect of vitamin E on pancreatic cancer

Type	Pancreatic cells	Dosing regimen	Statistically significant effect (compared to negative control)	Ref.
VES	AsPC-1, COLO 357, PANC-1	10-80 μM; 24, 48, 72 h	↓ Proliferation; ↑ Apoptosis; ↑ Cell cycle arrest; ↓Antiapoptotic markers	[31]
VES	LPC 1-7 (Primary Culture)	0.001-1 μM; 48 h	↓ Proliferation	[32]
VES	MIA PaCa-2	0.000023 μM; 24, 48, 72 h	↓ Proliferation	[33]
α-TPS	BxPC-3, Capan-1,MIA PaCa-2, PANC1, PSN-1	5-500 μM; 72h	↓ Proliferation	[34]
α-TPS, PAH-SS-PLGA-TOS	Pan02	1.45-232.2 μM; 48 h	↓ Proliferation; ↑ Apoptosis; ↑ Cell cycle arrest	[35]
α-TP	Capan-1, Capan-2	500 μM; 18 h	↓ NF-κB activity; ↓ IL-6; ↓ IL-8	[36]
α-TP, α-TT, β-TT, γ-TT, δ-TT	AsPC1, MIA PaCa-2	0-100 μM; 72 h	↓ Proliferation; ↑ Apoptosis;↓ NF-κB activity; ↓ NF-κB DNA binding activity; ↓Antiapoptotic markers	[39]
γ-TT, δ-TT	BxPC-3, MIA PaCa-2, PANC-1, Panc 28	10, 20, 40, 60, 80, 100 μM; 24 h	↑ Apoptosis; ↓ MAPK related markers	[40]
γ-TT	BxPC-3, MIA PaCa-2, PANC-1	10, 50 μM; 48, 96, 144 h	↓ Proliferation; ↓ NF-κB activity; ↓Antiapoptotic markers; ↓Angiogenesis markers; ↓ Invasion markers	[41]
γ-TT	BxPC-3, MIA PaCa-2, PANC-1	40 μM; 2, 4, 6 h	↑ Apoptosis	[12]
-TT	BxPC-3, MIA PaCa-2, SW1990	0-50μM; 24, 48, 72h	↓ Proliferation; ↑ Cell cycle arrest; ↓ MAPK related markers	[43]
δ-TT	BxPC-3, MIA PaCa-2, PANC-1	0-64 μM; 24-72 h	↓ Proliferation; ↑ Apoptosis	[44]
δ-TT	Human pancreatic cancer cells from ATCC	2.5-80 μM; 48 h	↓ Proliferation	[45]
δ-TT	PANC-1	12.5 μM; 48 h	↓ Proliferation	[46]
δ-TT	MIA PaCa-2	50 μM; 0-12 h	↓ Proliferation; ↑ Apoptosis; = Antiapoptotic markers	[47]
δ-TT	MIA PaCa-2, PCSCs	10-100 μM; 72 h	↓ MAPK related markers; ↓ Invasion markers; ↓ Angiogenesis markers	[48]
δ-TT	AsPc-1, BxPC-3, MIA PaCa-2, PANC-1, SW1990	20-100 μM; 72 h	↓ Proliferation; ↑ Apoptosis	[42]

“=” represents no difference; “↑” represents increase; “↓” represents reduction; PAH-SS-PLGA-TOS: Poly (allylamine)-citraconic anhydride-poly(lactic-co-glycolic acid)-cystamine micelle-α-tocopheryl succinate conjugate; α-TP: Alpha tocopherol; β-TT: Beta tocotrienol; γ-TT: Gamma tocotrienol; δ-TT: Delta tocotrienol; LPC: Low passage primary pancreatic cancer cells; ATCC: American Type Culture Collection; PCSC: Pancreatic cancer stem cells; NF-kappa B: Nuclear factor kappa-light-chain-enhancer of activated B cells; IL: Interleukin; MAPK: Mitogen-activated protein kinase.

Table 2 In vivo studies investigating effect of vitamin E on pancreatic cancer

Type	Model	Dosing regimen	Statistically significant effect (compared to negative control)	Ref.
δ-TT	Subcutaneous xenograft of MIA PaCa-2 induced pancreatic tumor in athymic nude mice	PO 100 mg/kg, 1 x/day for 3 wk	↓ Tumor volume; ↓ Proliferation markers; ↓ MAPK related markers	[43]
δ-TT	Subcutaneous xenograft of MIA PaCa-2 induced pancreatic tumor in athymic nude mice	PO 200 mg/kg, 2 x/day during weekday & 1 x/day during weekend for 4 wk	↓ Tumor volume; ↑ Apoptotic markers	[42]
δ-TT	Subcutaneous xenograft of L3.6pl cells and PCSC- induced pancreatic tumor in athymic nude mice	PO 200 mg/kg, 2x/day for 4 wk	↓ Tumor volume; ↓ Proliferation markers; ↑ Apoptotic markers; ↓ Invasion markers; ↓ Angiogenesis markers	[48]
δ-TT	Orthotopic xenograft of MIA PaCa-2 induced pancreatic tumor in athymic nude mice	PO 400 mg/kg, 1 x/day for 28 d	↓ Tumor volume; ↓ Proliferation markers; ↓ NF-κB activity; ↓ Invasion markers; ↓ Angiogenesis markers	[41]
δ-TT	LSLKrasG12D/+; LSLTrp53R172H/+; Pdx-1-Cre (KPC) transgenic mice	PO 200 mg/kg, 2 x/day for 12 wk	↑ Survival; ↓ Tumor volume; = Body weight; ↓ Proliferation markers; ↑ Apoptotic markers; ↓ MAPK related markers	[49]
δ-TT	LSLKrasG12D/+; Pdx-1-Cre transgenic mice	PO 200 mg/kg, 2 x/day for 12 mo	↑ Apoptotic markers	[47]
δ-TT	LSLKrasG12D/+; Pdx-1-Cre transgenic mice	PO 200 mg/kg, 2 x/day for 12 mo	↑ Survival; ↓ Tumor progression; = Body weight; ↑ Apoptotic markers; ↓ NF-κB markers; ↓ MAPK related markers	[50]
δ-TT	Orthotopic xenograft of MIA PaCa-2 induced pancreatic tumours in athymic nude mice	PO 50-100 mg/kg, 2 x/day during weekday & 1 x/day during weekend for 6 wk	↑ δ-TT concentration in pancreas; = Body weight; = Histopathology	[51]
α-TT, β-TT, γ-TT, δ-TT	Subcutaneous xenograft of AsPC-1 induced pancreatic tumor in SCID mice	PO 200 mg/kg, 2 x/day for 4 wk	↓ Tumor volume; ↑ Apoptotic markers; ↓ Antiapoptotic markers; ↓ NF-κB activity and markers	[39]
α-TP	N-nitrosobis (2-oxopropyl) amine-induced pancreatic cancer in Syrian hamster	PO 4 mg/kg, 3 x/wk for 12 wk	= Tumor incidence; = Body weight; ↓ Liver metastasis incidence; = Liver metastasis number; = Liver metastasis size	[37]
α-TP	N-nitrosobis (2-oxopropyl) amine-induced pancreatic cancer in Syrian hamster	PO 4 mg/kg, 3 x/wk for 12 wk	= Tumor incidence; = Body weight;	[38]

“=” represents no difference; “↑” represents increase; “↓” represents reduction; α-TP: Alpha tocopherol; α-TT: Alpha tocotrienol; γ-TT: Gamma tocotrienol; δ-TT: Delta tocotrienol; SCID: Severe-combined immunodeficient; PO: Oral administration; PCSC: Pancreatic cancer stem cells; MAPK: Mitogen-activated protein kinase; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells.