6-Shogaol induces apoptosis in human colorectal carcinoma cells via ROS production, caspase activation, and GADD 153 expression.
Ginger, the rhizome of Zingiber officinale, is a traditional medicine with anti-inflammatory and anticarcinogenic properties. This study examined the growth inhibitory effects of the structurally related compounds 6-gingerol and 6-shogaol on human cancer cells. 6-Shogaol [1-(4-hydroxy-3-methoxyphenyl)-4-decen-3-one] inhibits the growth of human cancer cells and induces apoptosis in COLO 205 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). ROS generation occurs in the early stages of 6-shogaol-induced apoptosis, preceding cytochrome c release, caspase activation, and DNA fragmentation. Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.
Pan
Min-Hsiung
MH
Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan. mhpan@mail.nkmu.edu.tw
Hsieh
Min-Chi
MC
Kuo
Jen-Min
JM
Lai
Ching-Shu
CS
Wu
Hou
H
Sang
Shengmin
S
Ho
Chi-Tang
CT
D000230:Adenocarcinoma / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002396:Catechols / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology; D015179:Colorectal Neoplasms / Q000473:pathology*; D005233:Fatty Alcohols / Q000302:isolation & purification / Q000494:pharmacology; D020939:Zingiber officinale; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000187:drug effects / Q000302:isolation & purification; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000187:drug effects / Q000235:genetics
D002396:Catechols; C497249:DDIT3 protein, human; D005233:Fatty Alcohols; D010936:Plant Extracts; D012334:RNA, Neoplasm; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; C040115:shogaol; C007845:gingerol; D020169:Caspases