Cytotoxic activity of a synthetic deoxypodophyllotoxin derivative with an opened D-ring.
Podophyllotoxin and its synthetic derivatives are valuable medicinal agents that have antitumor, insecticidal, and antifungal properties. We previously synthesized a deoxypodophyllotoxin derivative with an opened D-ring (DPD) exhibiting potent insecticidal activity. This article was firstly performed to identify the cytotoxicity of DPD toward human cancer cell lines (SGC7901, HeLa, and A549) and normal cell line (HEK293T) using MTT assay. DPD showed potent cytotoxicity against human cancer lines (HeLa and A549) and less cytotoxicity against normal cell lines HEK293T. DPD could also induce the cell cycle arrest at G2/M phase in HeLa cells and significantly increase the phosphorylation (Tyr 15) of CDC2 leading to inactivation of CDC2. The effects of DPD on cellular microtubule networks were detected using immunofluorescence technique in HeLa cells. The immunofluorescence results showed DPD influenced the arrangement and organization of cellular microtubule networks in HeLa cells. Microtubules are long, hollow cylinders made up of polymerized tubulin dimers. Total microtubules were separated after DPD treatment. Western blot results showed that the free polymerized tubulin dimers were obviously increased after DPD treatment. DPD may be a good drug candidate with the therapeutic potential to human cancer by affecting microtubule polymerization.
a Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education , College of Life Science, Hebei University , Baoding , China.
Chuan
C
Chen
a Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education , College of Life Science, Hebei University , Baoding , China.
Cui-Cui
CC
Wang
a Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education , College of Life Science, Hebei University , Baoding , China.
Zhong
Z
Wang
a Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education , College of Life Science, Hebei University , Baoding , China.
Wen-Yue
WY
Geng
b Laboratory of Pharmaceutical Design & Synthesis , College of Sciences, Northwest A&F University , Yangling , China.
Hui
H
Xu
a Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education , College of Life Science, Hebei University , Baoding , China.
Xiao-Mei
XM
Song
a Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education , College of Life Science, Hebei University , Baoding , China.
Du-Qiang
DQ
Luo
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal; D005047:Etoposide / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008870:Microtubules / Q000187:drug effects; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D014404:Tubulin; C014451:deoxypodophyllotoxin; D005047:Etoposide; D011034:Podophyllotoxin
MTT assay; cell cycle; deoxypodophyllotoxin derivative; microtubule