title: Novel mechanisms involving chemically modified tetracycline 3  cytotoxicity.
abstract: Chemically modified tetracycline 3 (CMT-3) is a potential anticancer drug because of its retained matrix metalloproteinases inhibitory property. In the present study,we showed that CMT-3 significantly inhibited the growth and proliferation of human hepatocellular carcinoma HepG2 cells. Novel mechanisms including increased intracellular autophagy level and high-mobility group box 1 (HMGB1)release were involved. In addition, a major Danshen ingredient, tanshinone IIA sodium sulfonate (TSN-SS),significantly increased the cytotoxic effects of CMT-3 in HepG2 cells. Combining CMT-3 with TSN-SS led to enhanced accumulation of endogenous LC3-II, but reduced HMGB1 cytoplasmic translocation. Altogether, these findings suggest that autophagy and HMGB1 release may play important roles in the anticancer effect of CMT-3. As an ovel candidate for cancer therapy, CMT-3 may be used in combination with TSN-SS, which possibly facilitates the execution of a death signal (e.g. autophagy) and prevents the survival of an inducer (e.g. HMGB1 cytoplasmic translocation), thus improving its therapeutic effect.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Jiaying
authors.initials: J
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.forename: Haichao
authors.initials: H
authors.lastname: Wang
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D004357:Drug Synergism; D024243:HMGB1 Protein / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology; D021381:Protein Transport; D013754:Tetracyclines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010616:Phenanthrenes; D013754:Tetracyclines; C117155:tetracycline CMT-3; C024894:tanshinone II A sodium sulfonate