title: Gold(III) porphyrin complex is more potent than cisplatin in inhibiting growth of nasopharyngeal carcinoma in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Yuk Fai
authors.initials: YF
authors.lastname: To
authors.forename: Raymond Wai-Yin
authors.initials: RW
authors.lastname: Sun
authors.forename: Yongxiong
authors.initials: Y
authors.lastname: Chen
authors.forename: Vera Sau-Fong
authors.initials: VS
authors.lastname: Chan
authors.forename: Wing-Yiu
authors.initials: WY
authors.lastname: Yu
authors.forename: Paul Kwong-Hang
authors.initials: PK
authors.lastname: Tam
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Che
authors.forename: Chen-Lung Steve
authors.initials: CL
authors.lastname: Lin
mesh_terms: 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
chemical_list: D011166:Porphyrins; D006046:Gold; D002945:Cisplatin