title: Alpha-tocopheryl succinate enhances doxorubicin-induced apoptosis in human gastric cancer cells via promotion of doxorubicin influx and suppression of doxorubicin efflux.
abstract: Doxorubicin (DOXO), a chemotherapy drug, is widely used in clinic for treating a variety of cancers. However, the treatment eventfully fails due to drug resistance and toxicity. Therefore, a combination strategy is needed to increase efficacy and reduce toxicity of DOXO. alpha-tocopheryl succinate (α-TOS) exhibits anticancer actions in vitro and in vivo. Here, we reported that combination of DOXO+α-TOS cooperatively acted to induce apoptosis in SGC-7901 cells. α-TOS enhanced cellular level of DOXO via promotion of DOXO influx and suppression of DOXO efflux. DOXO induced MDR1 mRNA and protein expression and α-TOS inhibited this event, indicating that α-TOS suppressed DOXO efflux via inhibition of MDR1. Furthermore, combination of DOXO+α-TOS induced increased levels of Fas and Bax protein expression and cleavage of caspase-8 and caspase-9, suggesting that combination treatment induced Fas/caspase-8 and Bax mediated mitochondria dependent apoptosis. Taken together, our results demonstrated that α-TOS enhanced DOXO anticancer efficiency via promotion of DOXO influx and suppression of MDR-1 mediated DOXO efflux.
authors.affiliation: Department of Nutrition and Food, Harbin Medical University, Harbin, China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiangwen
authors.initials: X
authors.lastname: Peng
authors.forename: Weiping
authors.initials: W
authors.lastname: Yu
authors.forename: Shaoying
authors.initials: S
authors.lastname: Hou
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Huang
authors.forename: Kun
authors.initials: K
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology*; D024505:Tocopherols / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; D004317:Doxorubicin; D024505:Tocopherols