TY - JOUR
T1 - Arecoline and the 30-100 kDa fraction of areca nut extract differentially regulate mTOR and respectively induce apoptosis and autophagy
T2 - A pilot study
AU - Liu, Shyun Yeu
AU - Lin, Mei Huei
AU - Hsu, Yu Rung
AU - Shih, Ya Yun
AU - Chiang, Wei Fan
AU - Lee, Chin Hai
AU - Chou, Ta Hsiung
AU - Liu, Young Chau
PY - 2008/11
Y1 - 2008/11
N2 - Areca nut (AN) is recognized as a human carcinogen; however, few studies of the cytotoxic effects of AN ingredients on cells have been reported. In Taiwan, AN, lime and inflorescence of Piper betle are the common components of betel quid (BQ). We recently noticed that extract of AN (ANE), but not those of lime and inflorescence of Piper betle, induces rounding cell morphology and nuclear shrinkage in different types of carcinoma cells. In this study, the rounding cell activity was first traced to the partially purified ≥10 kDa fraction (ANE ≥ 10 K) and subsequently to the 30-100 kDa fraction (ANE 30-100 K). ANE and ANE ≥10 K stimulated nuclear shrinkage (P <0.001 in both cases) and the clearance of the cytoplasm. ANE, ANE ≥ 10 K, and ANE 30-100 K induced the cleavage of LC3-I (P <0.05, 0.01, and 0.05, respectively) and the emergence of autophagic vacuoles (AVs) and acidic vesicles. On the other hand, arecoline (Are, the major alkaloid of AN) triggered caspase-3 activation, peri-nuclear chromatin condensation, and micronucleation. Meanwhile, ANE 30-100 K, but not Are, inhibited the phosphorylation of the mammalian target of rapamycin (mTOR)-Ser2448. In conclusion, this study demonstrates that different AN ingredients exerting differential impact on mTOR-Ser2448 phosphorylation are capable of triggering apoptosis and autophagy.
AB - Areca nut (AN) is recognized as a human carcinogen; however, few studies of the cytotoxic effects of AN ingredients on cells have been reported. In Taiwan, AN, lime and inflorescence of Piper betle are the common components of betel quid (BQ). We recently noticed that extract of AN (ANE), but not those of lime and inflorescence of Piper betle, induces rounding cell morphology and nuclear shrinkage in different types of carcinoma cells. In this study, the rounding cell activity was first traced to the partially purified ≥10 kDa fraction (ANE ≥ 10 K) and subsequently to the 30-100 kDa fraction (ANE 30-100 K). ANE and ANE ≥10 K stimulated nuclear shrinkage (P <0.001 in both cases) and the clearance of the cytoplasm. ANE, ANE ≥ 10 K, and ANE 30-100 K induced the cleavage of LC3-I (P <0.05, 0.01, and 0.05, respectively) and the emergence of autophagic vacuoles (AVs) and acidic vesicles. On the other hand, arecoline (Are, the major alkaloid of AN) triggered caspase-3 activation, peri-nuclear chromatin condensation, and micronucleation. Meanwhile, ANE 30-100 K, but not Are, inhibited the phosphorylation of the mammalian target of rapamycin (mTOR)-Ser2448. In conclusion, this study demonstrates that different AN ingredients exerting differential impact on mTOR-Ser2448 phosphorylation are capable of triggering apoptosis and autophagy.
KW - Apoptosis
KW - Areca nut
KW - Arecoline
KW - Autophagy
KW - Mammalian target of rapamycin (mTOR)
UR - http://www.scopus.com/inward/record.url?scp=56349148226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56349148226&partnerID=8YFLogxK
U2 - 10.1007/s11373-008-9273-8
DO - 10.1007/s11373-008-9273-8
M3 - Article
C2 - 18668345
AN - SCOPUS:56349148226
SN - 1021-7770
VL - 15
SP - 823
EP - 831
JO - Journal of Biomedical Science
JF - Journal of Biomedical Science
IS - 6
ER -