title: Shikonin Derivative DMAKO-05 Inhibits Akt Signal Activation and Melanoma Proliferation.
abstract: DMAKO-05((S)-1-((5E,8E)-5,8-bis(hydroxyimino)-1,4-dimethoxy-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 3-methylbutanoate) is a novel oxime derivative of shikonin, the major component extracted from Chinese herb Lithospermun erythrorhizon. Here, we report that DMAKO-05 had an antitumor activity against mouse melanoma cell line B16F0. Our studies indicated that DMAKO-05 not only inhibited B16F0 proliferation and migration but also led to cell cycle arrest at G1 phase and cell apoptosis, in which DMAKO-05 triggered mitochondrial-mediated apoptosis signal including caspase-9/3 and PARP. In response to DMAKO-05 treatment, the Akt-mediated survival signals were remarkably attenuated in B16F0 cells. Collectively, DMAKO-05 has a strong cytotoxicity in B16F0 cells via inhibiting Akt activation, inducing G1 arrest, and promoting B16F0 cell apoptosis. DMAKO-05 might serve as a potential candidate lead compound for melanoma.
authors.affiliation: School of Pharmacy, Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200 240, China.
authors.forename: Yao-Yao
authors.initials: YY
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200 240, China.
authors.forename: Hui-Qiong
authors.initials: HQ
authors.lastname: He
authors.affiliation: School of Pharmacy, Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200 240, China.
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Cui
authors.affiliation: School of Pharmacy, Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200 240, China.
authors.forename: Yun-Juan
authors.initials: YJ
authors.lastname: Nie
authors.affiliation: School of Pharmacy, Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200 240, China.
authors.forename: Ya-Xian
authors.initials: YX
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Rd., Bengbu, Anhui, 233 000, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 209 Tongshan Rd., Xuzhou, Jiangsu Province, 221 004, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 209 Tongshan Rd., Xuzhou, Jiangsu Province, 221 004, China.
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200 240, China.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Ye
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Rd., Bengbu, Anhui, 233 000, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200 240, China.
authors.forename: Shao-Shun
authors.initials: SS
authors.lastname: Li
authors.affiliation: School of Pharmacy, Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200 240, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; C016101:shikonin; D051057:Proto-Oncogene Proteins c-akt
keywords: DMAKO-05; apoptosis; cell cycle arrest; cytotoxicity; melanoma cell B16F0; shikonin