title: Poly (γ, L-glutamic acid)-cisplatin bioconjugate exhibits potent antitumor activity with low toxicity: a comparative study with clinically used platinum derivatives.
abstract: We have recently synthesized a new platinum derivative, poly (γ, L-glutamic acid)-cisplatin conjugate (γ-PGA-CDDP), and shown that it displayed remarkable antitumor activity against breast tumor in a mouse model. The purpose of this study is to systematically compare this new drug with three platinum derivatives currently used in the clinic: cisplatin, carboplatin and oxaliplatin. Here, we show that γ-PGA-CDDP displays impressive antitumor activity over the current clinically used platinum drugs. More interestingly and more importantly, γ-PGA-CDDP conjugate significantly reduces cytotoxicity, mitigates oxidative stress and improves antioxidative capability in vivo. Animals treated with γ-PGA-CDDP display the same profile of body weight as the control animals, while the tumors in γ-PGA-CDDP-treated animals are significantly suppressed compared with those treated with carboplatin and oxaliplatin. Our data suggest that γ-PGA could be used as an effective carrier for drug delivery and that γ-PGA-CDDP conjugate may have potential therapeutic applications in human cancers that are sensitive to treatment with CDDP-based chemotherapy such as ovarian cancer.
authors.affiliation: Molecular Biology Laboratory, School of Life Science, East China Normal University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Feng
authors.forename: Yuping
authors.initials: Y
authors.lastname: Lai
authors.forename: Haifeng
authors.initials: H
authors.lastname: Ye
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Xu Guang
authors.initials: XG
authors.lastname: Xi
authors.forename: Zirong
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D016190:Carboplatin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C511775:poly(gamma-glutamic acid); D000077150:Oxaliplatin; D011099:Polyglutamic Acid; D016190:Carboplatin; D002945:Cisplatin
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