Cellular pharmacological properties of gold(III) porphyrin 1a, a potential anticancer drug lead.
The development of gold(III) complexes as potential anticancer drugs with higher cytotoxicity and fewer side effects than existing metal anticancer drugs has been actively pursued in recent years. In this study, we explored the cellular pharmacological properties of gold(III) porphyrin 1a, an anticancer drug lead we previously described. The cytotoxicity study of gold(III) porphyrin 1a by naphthol blue black (NBB) staining assay demonstrated that the higher cytotoxicity of gold(III) porphyrin 1a was not related to its photosensitizing activity. Serum dependent test revealed that serum proteins exhibited lesser effects on the activity of gold(III) porphyrin 1a. In addition, in vivo and in vitro binding assays showed that gold(III) porphyrin 1a acted on DNA noncovalently, which was differently from cisplatin. Flow cytometric study indicated that gold(III) porphyrin 1a inhibited cell growth partly through abrogating cell cycle at G(0)-G(1), and induced apoptosis in SUNE1 cells. The enhanced expression of p53, a cell cycle-controlling and apoptosis-related protein, further demonstrated that the cell cycle arrest and apoptosis induced by gold porphyrin 1a were p53 dependent. Our results highlighted the potential of gold(III) porphyrin 1a as an anticancer drug.
Wang
Ying
Y
Department of Chemistry and Open Laboratory of Chemical Biology, The University of Hong Kong, Hong Kong SAR, China.
He
Qing-Yu
QY
Sun
Raymond Wai-Yin
RW
Che
Chi-Ming
CM
Chiu
Jen-Fu
JF
D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001667:Binding, Competitive; D015153:Blotting, Western; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology; D018360:Crystallography, X-Ray; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005312:Fetal Blood / Q000737:chemistry; D017612:Gold Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008665:Metalloporphyrins / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000873:Anthracenes; D000970:Antineoplastic Agents; D003470:Culture Media; D004273:DNA, Neoplasm; D017612:Gold Compounds; D008665:Metalloporphyrins; D016159:Tumor Suppressor Protein p53; C508665:gold (III) porphyrin 1a; D010569:Perylene; C004965:hypericin; D002945:Cisplatin