PMID- 30896562
OWN - NLM
STAT- MEDLINE
DCOM- 20190826
LR  - 20211204
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 132
IP  - 9
DP  - 2019 May 5
TI  - Inhibitory effects of petasin on human colon carcinoma cells mediated by 
      inactivation of Akt/mTOR pathway.
PG  - 1071-1078
LID - 10.1097/CM9.0000000000000199 [doi]
AB  - BACKGROUND: Colorectal cancer is the third most common cancer worldwide and still 
      lack of effective therapy so far. Petasin, a natural product found in plants of 
      the genus Petasites, has been reported to possess anticancer activity. The 
      present study aimed to investigate the anticolon cancer activity of petasin both 
      in vitro and in vivo. The molecular mechanism of petasin was also further 
      explored. METHODS: Caco-2, LoVo, SW-620, and HT-29 cell lines were used to detect 
      the inhibitory effect of petasin on colon cancer proliferation. Cell viability 
      was determined using the MTT 
      (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell 
      apoptosis was analyzed by flow cytometry. Hoechst 33258 staining was used to 
      visualize morphological changes. Cell migration was assessed using a 
      wound-healing migration assay, and cell invasion was investigated using Transwell 
      chambers. Western blotting assays were employed to evaluate the expression levels 
      of proteins in the protein kinase B/mammalian target of rapamycin (Akt/mTOR) 
      signaling pathway. Finally, in vivo activity of petasin was evaluated using the 
      SW-620 subcutaneous tumor model established in Balb/c nude mice. Twelve rats were 
      randomly divided into control group and 10 mg/kg petasin group. The tumor volume 
      was calculated every 7 days for 28 days. Terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to assess 
      the apoptotic effect of petasin. Differences between two groups were assessed by 
      analysis of independent-sample t tests. RESULTS: Petasin significantly inhibited 
      the proliferation of human colon carcinoma cell lines, induced apoptosis, and 
      suppressed migration and invasion in SW-620 cells. Western blotting results 
      showed that petasin decreased the phosphorylation of Akt (1.01 +/- 0.16 vs. 
      0.74 +/- 0.06, P = 0.042), mTOR (0.71 +/- 0.12 vs. 0.32 +/- 0.11, P = 0.013), and 
      P70S6K (1.23 +/- 0.21 vs. 0.85 +/- 0.14, P = 0.008), elevated the expression of 
      caspase-3 (0.41 +/- 0.09 vs. 0.74 +/- 0.12, P = 0.018) and caspase-9 (1.10 +/- 0.27 vs. 
      1.98 +/- 0.22, P = 0.009), decreased the Bcl-2 protein (2.75 +/- 0.47 vs. 
      1.51 +/- 0.36, P = 0.008), downregulated the expression of matrix metalloproteinase 
      (MMP)-3 (1.51 +/- 0.31 vs. 0.82 +/- 0.11, P = 0.021) and MMP-9 (1.56 +/- 0.32 vs. 
      0.94 +/- 0.15, P = 0.039) in SW-620 cell. In vivo, 10 mg/kg petasin inhibited tumor 
      growth in Balb/c nude mice (924.18 +/- 101.23 vs. 577.67 +/- 75.12 mm at day 28, 
      P = 0.001) and induced apoptosis (3.6 +/- 0.7% vs. 36.0 +/- 4.9%, P = 0.001) in tumor 
      tissues. CONCLUSIONS: Petasin inhibits the proliferation of colon cancer SW-620 
      cells via inactivating the Akt/mTOR pathway. Our findings suggest petasin as a 
      potential candidate for colon cancer therapy.
FAU - Lyu, Xi
AU  - Lyu X
AD  - The 5th Department of General Surgery, Lanzhou University Second Hospital, 
      Lanzhou, Gansu 730030, China.
FAU - Song, Ai-Lin
AU  - Song AL
AD  - The 5th Department of General Surgery, Lanzhou University Second Hospital, 
      Lanzhou, Gansu 730030, China.
FAU - Bai, Yin-Liang
AU  - Bai YL
AD  - Department of Pharmacy, Lanzhou University Second Hospital, Lanzhou, Gansu 
      730030, China.
FAU - Xu, Xiao-Dong
AU  - Xu XD
AD  - The 2nd Department of General Surgery, Lanzhou University Second Hospital, 
      Lanzhou, Gansu 730030, China.
FAU - He, Dong-Qiang
AU  - He DQ
AD  - The 5th Department of General Surgery, Lanzhou University Second Hospital, 
      Lanzhou, Gansu 730030, China.
FAU - Zhang, You-Cheng
AU  - Zhang YC
AD  - The 2nd Department of General Surgery, Lanzhou University Second Hospital, 
      Lanzhou, Gansu 730030, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Sesquiterpenes)
RN  - 9Z0Q32J0QC (petasin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
MH  - Animals
MH  - Antineoplastic Agents/*therapeutic use
MH  - Apoptosis/drug effects
MH  - Caco-2 Cells
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - HT29 Cells
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Sesquiterpenes/*therapeutic use
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
PMC - PMC6595872
EDAT- 2019/03/22 06:00
MHDA- 2019/08/27 06:00
PMCR- 2019/05/05
CRDT- 2019/03/22 06:00
PHST- 2019/03/22 06:00 [pubmed]
PHST- 2019/08/27 06:00 [medline]
PHST- 2019/03/22 06:00 [entrez]
PHST- 2019/05/05 00:00 [pmc-release]
AID - CMJ-2018-316 [pii]
AID - 10.1097/CM9.0000000000000199 [doi]
PST - ppublish
SO  - Chin Med J (Engl). 2019 May 5;132(9):1071-1078. doi: 
      10.1097/CM9.0000000000000199.