Deacetylisovaltratum disrupts microtubule dynamics and causes G2/M-phase arrest in human gastric cancer cells in vitro.
OBJECTIVE
Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms.


METHODS
Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry. Protein levels were analyzed by Western blotting. Tubulin polymerization assays and immunofluorescence were used to characterize the tubulin polymerization process.


RESULTS
DI inhibited the cell viability of AGS and HGC-27 cells in a dose- and time-dependent manner with IC50values of 12.0 and 28.8 μmol/L, respectively, at 24 h of treatment. Treatment with DI (10-100 μmol/L) dose-dependently promoted tubulin polymerization, and induced significant G2/M cell cycle arrest in AGS and HGC-27 cells. Moreover, DI treatment disrupted mitochondrial membrane potential and induced caspase-dependent apoptosis in AGS and HGC-27 cells.


CONCLUSIONS
DI induces G2/M-phase arrest by disrupting tubulin polymerization in human gastric cancer cells, which highlights its potent anti-cancer activity and potential application in gastric cancer therapy.
Laboratory of Clinical Pharmacology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou 310006, China.|Hangzhou Translational Medicine Research Center, Hangzhou First People's Hospital, Hangzhou 310006, China.|Department of Pharmacy, Hangzhou Geriatric Hospital, Hangzhou 310022, China.|Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou 310006, China.
Dan
D
Zhang
Laboratory of Clinical Pharmacology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou 310006, China.|Hangzhou Translational Medicine Research Center, Hangzhou First People's Hospital, Hangzhou 310006, China.|Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou 310006, China.
Bo
B
Zhang
Department of Hepatopancreatobiliary Surgery, Hangzhou First People's Hospital, Hangzhou 310006, China.
Li-Xin
LX
Zhou
Department of Pharmacy, Hangzhou Geriatric Hospital, Hangzhou 310022, China.
Jun
J
Zhao
Laboratory of Clinical Pharmacology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou 310006, China.|Hangzhou Translational Medicine Research Center, Hangzhou First People's Hospital, Hangzhou 310006, China.
You-You
YY
Yan
Laboratory of Clinical Pharmacology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou 310006, China.|Hangzhou Translational Medicine Research Center, Hangzhou First People's Hospital, Hangzhou 310006, China.|Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou 310006, China.
Yang-Ling
YL
Li
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Jian-Mei
JM
Zeng
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Lin-Ling
LL
Wang
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Bo
B
Yang
Laboratory of Clinical Pharmacology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou 310006, China.|Hangzhou Translational Medicine Research Center, Hangzhou First People's Hospital, Hangzhou 310006, China.|Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou 310006, China.|College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Neng-Ming
NM
Lin
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy*; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014404:Tubulin; D050257:Tubulin Modulators
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