Dipyrithione induces cell-cycle arrest and apoptosis in four cancer cell lines in vitro and inhibits tumor growth in a mouse model.

Abstract

BACKGROUND:

Dipyrithione (PTS2) is widely used as a bactericide and fungicide. Here, we investigated whether PTS2 has broad-spectrum antitumor activity by studying its cytotoxicity and proapoptotic effects in four cancer cell lines.

METHODS:

We used MTT assays and trypan blue staining to test the viability of cancer cell lines. Hoechst 33258 and DAPI staining were used to observe cell apoptosis. Cell-cycle percentages were analyzed by flow cytometry. Apoptosis was assayed using caspase-3 and poly (ADP-ribose) polymerase (PARP) combined with Western blotting. Student's t-test was used for statistical analysis.

RESULTS:

PTS2 inhibited proliferation in four cancer cell lines in a dose-dependent manner. Treated cells showed shrinkage, irregular fragments, condensed and dispersed blue fluorescent particles compared with control cells. PTS2 induced cycle-arrest and death. Cleavage of caspase-9, caspase-3, and PARP were detected in PTS2-treated cells. Antitumor activity of PTS2 was more effective against widely used cancer drugs and its precursor.

CONCLUSIONS:

PTS2 appears to have novel cytotoxicity and potent broad-spectrum antitumor activity, which suggests its potential as the basis of an anticancer drug.

• Authors: Yumei Fan, Caizhi Liu, Yongmao Huang, Jie Zhang, Linlin Cai, Shengnan Wang, Yongze Zhang, Xianglin Duan, Zhimin Yin
• Journal: BMC pharmacology & toxicology (BMC Pharmacol Toxicol) Vol. 14 Pg. 54 (Oct 21 2013) ISSN: 2050-6511 [Electronic] England
• PMID: 24139500 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Pyridines
• dipyrithione

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Proliferation (drug effects)
• Flow Cytometry
• Humans
• K562 Cells
• Male
• Mice
• Mice, Inbred ICR
• Molecular Structure
• Pyridines (pharmacology)
• U937 Cells
• Xenograft Model Antitumor Assays