Page 241 - 2014 Printable Abstract Book
P. 241
SOD3 (p<0.04). TH-curc improved skin elasticity at the burn site following TBI+2β from Day 60, 120, 150,
and 180 (5.99, 3.61, 3.18, 2.51 MegaPascals and and 9.04, 5.89, 6.38, 5.59 MegaPascals, respectively;
p≤0.04). Additionally, TH-curc improved skin retraction from Day 120, 150, 180 at the burn site (1.20, 5.53,
2.62 seconds and 17.18, 37.10, 16.19 seconds; p≤0.02) and burn periphery (1.55, 0.85, 1.55 seconds and
16.13, 18.68, 33.44 seconds; p≤0.04). These data suggest a reduction in fibrosis induced by TBI+2β.
Conclusions: Topical 10% TH-curc is a promising mitigator for acute skin injury and fibrosis from combined
radiation skin injury. Further studies are required to establish the mechanism of this mitigation and to
optimize therapeutic benefit. Support: Center for Medical Countermeasures against Radiation Program
(NIAID-U19-AI091036)
(PS4-12) Phytochemicals inhibit cancer cell proliferation by down-regulating the expression of
glycolytic genes hkII, ldhb, and pkm2. Amanda L. Kalen; Jaimee C. Eckers, PhD; Wusheng Xiao, MS;
Ehab H. Sarsour, PhD; and Prabhat C. Goswami, PhD, The University of Iowa, Iowa City, IA
Phytochemicals, such as curcumin and piperlongumine, are known to have anti-proliferative
properties. Curcumin ((1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a
polyphenol from the ginger family and piperlongumine (5,6-Dihydro-1-[(2E)-1-oxo-3-(3,4,5-
trimethoxyphenyl)-2-propen-1-yl]-2(1H)-Pyridinone) is an alkaloid derived from the Asian long pepper.
This study investigates the hypothesis that glycolysis regulates phytochemical-induced inhibition of cancer
cell proliferation and radiation response. To test this hypothesis, we treated Cal27 human head and neck
squamous carcinoma cells with curcumin (160 fmol/cell), piperlongumine (40 fmol/cell) or combination.
Results showed plating efficiency (PE) decreased significantly in curcumin (8%), piperlongumine (12%),
and combined treatment (6%) compared to untreated control (27%). The anti-proliferative effects of
curcumin and piperlongumine were also observed in PANC-1 and MIA PaCa-2 human pancreatic cancer
cells. PE for PANC-1 was found to be 47% in control cells, 8% in curcumin, 31% in piperlongumine, and 7%
in combination treatment. Similarly, phytochemcials also reduced the PE of MIA PaCa-2 cells (40% in
control cells, 1.7% in curcumin, 18% in piperlongumine, and 1.2% in combination treatment). The
decrease in PE was accompanied with a significant increase in the percentage of G2-cells. Interestingly,
the same treatments did not affect PE of normal human fibroblasts. Results from a quantitative RT-PCR
assay showed the phytochemical combination treatment significantly down-regulated the expression of
glycolytic genes in Cal27 cells: hexokinase II (hkII, 5-fold), lactate dehydrogenase b (ldhb, 8-fold), and
pyruvate kinase M2 (pkm2, 1.5-fold). Additionally, pretreatment with curcumin or piperlongumine
sensitized Cal27cells to ionizing radiation (2 Gy) induced cell killing: 52% survival in radiation alone
compared to 19% and 17% survival in curcumin and piperlongumine-treated irradiated cells, respectively.
These results suggest that the anti-proliferative and radiosensitizing properties of curcumin and
piperlongumine could be due to their ability to perturb glycolysis and redistribute cancer cells to the
radiosensitive G2-phase. (NIH 2R01CA111365)
239 | P a g e
and 180 (5.99, 3.61, 3.18, 2.51 MegaPascals and and 9.04, 5.89, 6.38, 5.59 MegaPascals, respectively;
p≤0.04). Additionally, TH-curc improved skin retraction from Day 120, 150, 180 at the burn site (1.20, 5.53,
2.62 seconds and 17.18, 37.10, 16.19 seconds; p≤0.02) and burn periphery (1.55, 0.85, 1.55 seconds and
16.13, 18.68, 33.44 seconds; p≤0.04). These data suggest a reduction in fibrosis induced by TBI+2β.
Conclusions: Topical 10% TH-curc is a promising mitigator for acute skin injury and fibrosis from combined
radiation skin injury. Further studies are required to establish the mechanism of this mitigation and to
optimize therapeutic benefit. Support: Center for Medical Countermeasures against Radiation Program
(NIAID-U19-AI091036)
(PS4-12) Phytochemicals inhibit cancer cell proliferation by down-regulating the expression of
glycolytic genes hkII, ldhb, and pkm2. Amanda L. Kalen; Jaimee C. Eckers, PhD; Wusheng Xiao, MS;
Ehab H. Sarsour, PhD; and Prabhat C. Goswami, PhD, The University of Iowa, Iowa City, IA
Phytochemicals, such as curcumin and piperlongumine, are known to have anti-proliferative
properties. Curcumin ((1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a
polyphenol from the ginger family and piperlongumine (5,6-Dihydro-1-[(2E)-1-oxo-3-(3,4,5-
trimethoxyphenyl)-2-propen-1-yl]-2(1H)-Pyridinone) is an alkaloid derived from the Asian long pepper.
This study investigates the hypothesis that glycolysis regulates phytochemical-induced inhibition of cancer
cell proliferation and radiation response. To test this hypothesis, we treated Cal27 human head and neck
squamous carcinoma cells with curcumin (160 fmol/cell), piperlongumine (40 fmol/cell) or combination.
Results showed plating efficiency (PE) decreased significantly in curcumin (8%), piperlongumine (12%),
and combined treatment (6%) compared to untreated control (27%). The anti-proliferative effects of
curcumin and piperlongumine were also observed in PANC-1 and MIA PaCa-2 human pancreatic cancer
cells. PE for PANC-1 was found to be 47% in control cells, 8% in curcumin, 31% in piperlongumine, and 7%
in combination treatment. Similarly, phytochemcials also reduced the PE of MIA PaCa-2 cells (40% in
control cells, 1.7% in curcumin, 18% in piperlongumine, and 1.2% in combination treatment). The
decrease in PE was accompanied with a significant increase in the percentage of G2-cells. Interestingly,
the same treatments did not affect PE of normal human fibroblasts. Results from a quantitative RT-PCR
assay showed the phytochemical combination treatment significantly down-regulated the expression of
glycolytic genes in Cal27 cells: hexokinase II (hkII, 5-fold), lactate dehydrogenase b (ldhb, 8-fold), and
pyruvate kinase M2 (pkm2, 1.5-fold). Additionally, pretreatment with curcumin or piperlongumine
sensitized Cal27cells to ionizing radiation (2 Gy) induced cell killing: 52% survival in radiation alone
compared to 19% and 17% survival in curcumin and piperlongumine-treated irradiated cells, respectively.
These results suggest that the anti-proliferative and radiosensitizing properties of curcumin and
piperlongumine could be due to their ability to perturb glycolysis and redistribute cancer cells to the
radiosensitive G2-phase. (NIH 2R01CA111365)
239 | P a g e
