Gold(III) porphyrin complex is more potent than cisplatin in inhibiting growth of nasopharyngeal carcinoma in vitro and in vivo.
Nasopharyngeal carcinoma (NPC) is a common neoplasm in Southeastern Asia, and cisplatin-containing regimens for combinational chemotherapy are widely used for treating locally recurrent or metastatic diseases. However, resistance to cisplatin is not infrequently seen and its associated side effects may be life-threatening. In this report, another metallo-pharmaceutical agent gold(III) porphyrin complex [Au(TPP)]Cl was investigated in comparison to cisplatin for its in vitro and in vivo anticancer effects. Through induction of the intrinsic apoptosis pathway, [Au(TPP)]Cl exhibited 100-fold higher potency than cisplatin in killing NPC cells, including cisplatin-sensitive and cisplatin-resistant variants, and also an variant harboring the Epstein-Barr virus. In addition, a safety concentration window was demonstrated, allowing [Au(TPP)]Cl to kill tumors with minimal cytotoxicity to noncancerous cells. More importantly, weekly intraperitoneal injection of 3 mg/kg [Au(TPP)]Cl was more effective than the same dose of cisplatin in inducing tumor apoptosis in vivo and remarkably inhibited tumor growth in animals without any noticeable side effect. [Au(TPP)]Cl therefore is a promising chemotherapeutic agent that deserves further development as a novel drug for the treatment of advanced NPC, in particular, for cases with cisplatin-resistance.
To
Yuk Fai
YF
Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Sun
Raymond Wai-Yin
RW
Chen
Yongxiong
Y
Chan
Vera Sau-Fong
VS
Yu
Wing-Yiu
WY
Tam
Paul Kwong-Hang
PK
Che
Chi-Ming
CM
Lin
Chen-Lung Steve
CL
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D006046:Gold / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008956:Models, Chemical; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D011166:Porphyrins / Q000008:administration & dosage*; D016896:Treatment Outcome
D011166:Porphyrins; D006046:Gold; D002945:Cisplatin