PMID- 32862572
OWN - NLM
STAT- MEDLINE
DCOM- 20210210
LR  - 20210210
IS  - 2241-6293 (Electronic)
IS  - 1107-0625 (Linking)
VI  - 25
IP  - 3
DP  - 2020 May-Jun
TI  - Lanostane inhibits the proliferation and bone metastasis of human breast cancer 
      cells via inhibition of Rho-associated kinase signaling.
PG  - 1323-1329
AB  - PURPOSE: This study was performed to investigate the effects of lanostane against 
      human breast cancer cells with emphasis on its potential to inhibit cancer cell 
      growth and metastasis along with understanding the underlying molecular mechanism 
      mediating the effects. METHODS: The SK-BR-3 normal breast line and the MB-157 
      breast cancer cell line were used in this study. MTT of cell growth was used to 
      determine the viability of cells under lanostane treatment. Colony formation 
      assay was used to analyze the clone forming capability of cancer cells when 
      treated with lanostane. DAPI and acridine orange (AO)/ethidium bromide (EB) 
      staining assays were performed for assessing the apoptic cell death. The level of 
      cellular apoptosis was further examined using flow cytometry. Wound healing and 
      transwell assays were performed to determine the migration and invasion of cancer 
      cells. Western blotting was used for determining the concentration of proteins of 
      interest. RESULTS: The lanostane treatment of cancer cells resulted in loss of 
      cell viability. The IC50 value was 15microM and the inhibitory effects were 
      dose-dependent. However, the inhibition of cell proliferation in normal breast 
      cells was comparatively lower. The antiproliferative effects of lanostane were 
      modulated through Bax/Bcl-2 pathway inducing apoptosis of cancer cells. 
      Furthermore, the lanostane rendered cancer cells less motile and reduced their 
      metastasis remarkably. The inhibition of cell metastasis was modulated through 
      Rho-associated kinases (ROCK) signaling pathway which is involved in metastasis 
      of breast cancer to bone tissues. Hence, the results suggested that lanostane 
      inhibited the breast cancer metastasis to bone. CONCLUSION: The results of the 
      present study are suggestive of anticancer effects of lanostene triterpene which 
      exerted its effects by inhibiting cell proliferation and metastasis of breast 
      cancer cells mediated through inactivation of Rho-associated kinase signaling. 
      The study holds promise to provide a lead for exploring the secondary 
      metabolite-based anticancer approach against various human malignancies.
FAU - Du, Yiqun
AU  - Du Y
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China.
FAU - Yan, Wangjun
AU  - Yan W
FAU - Wang, Zhicheng
AU  - Wang Z
FAU - Wang, Chenchen
AU  - Wang C
FAU - Huang, Mingzhu
AU  - Huang M
FAU - Tao, Zhonghua
AU  - Tao Z
FAU - Wu, Zhiqiang
AU  - Wu Z
LA  - eng
PT  - Journal Article
PL  - Cyprus
TA  - J BUON
JT  - Journal of B.U.ON. : official journal of the Balkan Union of Oncology
JID - 100883428
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Bone Neoplasms/*drug therapy/metabolism
MH  - Breast Neoplasms/*drug therapy/metabolism
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/*drug effects
MH  - Female
MH  - Humans
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Signal Transduction/*drug effects
MH  - bcl-2-Associated X Protein/metabolism
MH  - rho-Associated Kinases/*metabolism
EDAT- 2020/08/31 06:00
MHDA- 2021/02/11 06:00
CRDT- 2020/08/31 06:00
PHST- 2020/08/31 06:00 [entrez]
PHST- 2020/08/31 06:00 [pubmed]
PHST- 2021/02/11 06:00 [medline]
PST - ppublish
SO  - J BUON. 2020 May-Jun;25(3):1323-1329.