Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms.
Ginger has been used throughout the world as spice, food and traditional herb. We found that 6-gingerol, a phenolic alkanone isolated from ginger, enhanced the TRAIL-induced viability reduction of gastric cancer cells while 6-gingerol alone affected viability only slightly. 6-Gingerol facilitated TRAIL-induced apoptosis by increasing TRAIL-induced caspase-3/7 activation. 6-Gingerol was shown to down-regulate the expression of cIAP1, which suppresses caspase-3/7 activity, by inhibiting TRAIL-induced NF-kappaB activation. As 6-shogaol has a chemical structure similar to 6-gingerol, we also assessed the effect of 6-shogaol on the viability of gastric cancer cells. Unlike 6-gingerol, 6-shogaol alone reduced the viability of gastric cancer cells. 6-Shogaol was shown to damage microtubules and induce mitotic arrest. These findings indicate for the first time that in gastric cancer cells, 6-gingerol enhances TRAIL-induced viability reduction by inhibiting TRAIL-induced NF-kappaB activation while 6-shogaol alone reduces viability by damaging microtubules.
Ishiguro
Kazuhiro
K
Molecular Biology and Pathogenesis of Gastroenterology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: kio@med.nagoya-u.ac.jp.
Ando
Takafumi
T
Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Maeda
Osamu
O
Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Ohmiya
Naoki
N
Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Niwa
Yasumasa
Y
Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Kadomatsu
Kenji
K
Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Goto
Hidemi
H
Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D005233:Fatty Alcohols / Q000494:pharmacology*; D020939:Zingiber officinale / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008870:Microtubules / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
D002396:Catechols; D005233:Fatty Alcohols; D016328:NF-kappa B; D010936:Plant Extracts; D053221:TNF-Related Apoptosis-Inducing Ligand; C040115:shogaol; C007845:gingerol; D053148:Caspase 3; D053179:Caspase 7