PMID- 34500742
OWN - NLM
STAT- MEDLINE
DCOM- 20211109
LR  - 20211109
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 26
IP  - 17
DP  - 2021 Sep 1
TI  - Anticancer Effects of Ursi Fel Extract and Its Active Compound, Ursodeoxycholic 
      Acid, in FRO Anaplastic Thyroid Cancer Cells.
LID - 10.3390/molecules26175309 [doi]
LID - 5309
AB  - Anaplastic thyroid cancer (ATC) is one of the most fatal human malignancies. Ursi 
      Fel (UF) is the bile of a brown bear that has been traditionally used for heat 
      clearance and toxin relief in Korean and Chinese medicines. In this study, we 
      determined the anticancer effects of a UF extract and its active compound, 
      ursodeoxycholic acid (UDCA), in FRO human ATC cells. FRO cells were treated with 
      UF extract and UDCA at different concentrations for various durations. Cell 
      viability was measured using an MTT assay. Cell apoptosis was investigated by 
      flow cytometric analysis following Annexin V and propidium iodide (PI) staining, 
      and Hoechst staining was used to observe nuclear fragmentation. The expression of 
      pro-apoptotic (Bax, caspase-3, cytochrome c, and PARP), anti-apoptotic (Bcl-2), 
      and angiogenetic (TGF-beta, VEGF, N-cadherin, and sirtuin-1) proteins and the 
      phosphorylation of Akt and mechanistic target of rapamycin (mTOR) were determined 
      by western blot analysis. Treatment with UF extract at 10, 25, and 50 mug/mL and 
      UDCA at 25, 50, and 100 muM/mL significantly inhibited the growth of FRO cells in 
      a dose-dependent manner. Flow cytometry and Hoechst staining revealed an increase 
      in the apoptosis of FRO cells mediated by UF extract and UDCA in a dose-dependent 
      manner. UF extract (25 and 50 mug) and UDCA (50 and 100 muM) significantly 
      increased the expression of Bax, caspase-3, cytochrome c, and PARP and inhibited 
      the expression of Bcl-2, TGF-beta, VEGF, N-cadherin, and sirtuin-1 in FRO cells. 
      Furthermore, UF extract and UDCA treatment stimulated Akt phosphorylation and 
      inhibited mTOR phosphorylation in these cells. These results indicate that UF 
      extract and UDCA exert anticancer properties in FRO cells by inducing apoptosis 
      and inhibiting angiogenesis via regulating the Akt/mTOR signaling pathway.
FAU - Jung, Hyo Won
AU  - Jung HW
AD  - Department of Herbology, College of Korean Medicine, Dongguk University, 
      Dongdae-ro 123, Gyeongju 38066, Korea.
FAU - Hwang, Ji Hye
AU  - Hwang JH
AUID- ORCID: 0000-0002-6304-1972
AD  - Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, 
      Gachon University, Seongnam 13120, Korea.
LA  - eng
PT  - Journal Article
DEP - 20210901
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Plant Extracts)
RN  - 724L30Y2QR (Ursodeoxycholic Acid)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/chemistry/isolation & 
      purification/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Molecular Structure
MH  - Plant Extracts/chemistry/isolation & purification/*pharmacology
MH  - Structure-Activity Relationship
MH  - Thyroid Carcinoma, Anaplastic/*drug therapy/pathology
MH  - Tumor Cells, Cultured
MH  - Ursidae
MH  - Ursodeoxycholic Acid/chemistry/isolation & purification/*pharmacology
PMC - PMC8434085
OTO - NOTNLM
OT  - Ursi Fel
OT  - angiogenesis
OT  - anticancer effect
OT  - apoptosis
OT  - thyroid cancer
OT  - ursodeoxycholic acid
COIS- The authors declare no conflict of interest regarding the publication of this 
      article.
EDAT- 2021/09/11 06:00
MHDA- 2021/11/10 06:00
PMCR- 2021/09/01
CRDT- 2021/09/10 01:01
PHST- 2021/04/24 00:00 [received]
PHST- 2021/08/01 00:00 [revised]
PHST- 2021/08/04 00:00 [accepted]
PHST- 2021/09/10 01:01 [entrez]
PHST- 2021/09/11 06:00 [pubmed]
PHST- 2021/11/10 06:00 [medline]
PHST- 2021/09/01 00:00 [pmc-release]
AID - molecules26175309 [pii]
AID - molecules-26-05309 [pii]
AID - 10.3390/molecules26175309 [doi]
PST - epublish
SO  - Molecules. 2021 Sep 1;26(17):5309. doi: 10.3390/molecules26175309.