In Vitro and In Vivo Studies of Non-Platinum-Based Halogenated Compounds as Potent Antitumor Agents for Natural Targeted Chemotherapy of Cancers.
Based on a molecular-mechanism-based anticancer drug discovery program enabled by an innovative femtomedicine approach, we have found a previously unknown class of non-platinum-based halogenated molecules (called FMD compounds) as potent antitumor agents for effective treatment of cancers. Here, we present in vitro and in vivo studies of the compounds for targeted chemotherapy of cervical, breast, ovarian, and lung cancers. Our results show that these FMD agents led to DNA damage, cell cycle arrest in the S phase, and apoptosis in cancer cells. We also observed that such a FMD compound caused an increase of reduced glutathione (GSH, an endogenous antioxidant) levels in human normal cells, while it largely depleted GSH in cancer cells. We correspondingly found that these FMD agents exhibited no or little toxicity toward normal cells/tissues, while causing significant cytotoxicity against cancer cells, as well as suppression and delay in tumor growth in mouse xenograft models of cervical, ovarian, breast and lung cancers. These compounds are therefore a previously undiscovered class of potent antitumor agents that can be translated into clinical trials for natural targeted chemotherapy of multiple cancers.
Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada ; Departments of Biology and Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada.
Qing-Bin
QB
Lu
Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada.
Qin-Rong
QR
Zhang
Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada.
Ning
N
Ou
Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada.
Chun-Rong
CR
Wang
Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada.
Jenny
J
Warrington
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D055808:Drug Discovery; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D006219:Halogens / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000188:drug therapy*; D017671:Platinum Compounds / Q000494:pharmacology*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D018675:Toxicity Tests; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D006219:Halogens; D017671:Platinum Compounds; D005978:Glutathione
Antitumor agents; Femtomedicine; Non-platinum-based compounds; Reductive DNA damage; Targeted chemotherapy