Shikonin Derivative DMAKO-05 Inhibits Akt Signal Activation and Melanoma Proliferation

Chemical Biology & Drug Design
Yao-Yao YangFeng Qian

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.

References

Apr 1, 1986·Biochemical Pharmacology·M G MillerG M Cohen
Jun 12, 2002·Current Treatment Options in Oncology·W Sun, L M Schuchter
Mar 16, 2004·Science·Yardena SamuelsVictor E Velculescu
Sep 3, 2004·The New England Journal of Medicine·Hensin TsaoArthur J Sober
Dec 24, 2004·The New England Journal of Medicine·Vincenzo de GiorgiBenvenuto Giannotti
Apr 21, 2005·The Journal of Clinical Investigation·Yakov ChudnovskyAmy E Adams
May 24, 2005·Biochemical Pharmacology·Nathalie Dias, Christian Bailly
Jun 1, 2007·The New England Journal of Medicine·Gary HudesUNKNOWN Global ARCC Trial
Jul 25, 2007·Journal of Cell Science·Haojie Huang, Donald J Tindall
Aug 12, 2008·Biochemical Pharmacology·Naghma KhanHasan Mukhtar
Jun 6, 2009·Pigment Cell & Melanoma Research·Subbarao V Madhunapantula, Gavin P Robertson
Dec 10, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael A DaviesJeffrey E Gershenwald
May 5, 2011·Biochimica Et Biophysica Acta·David E A Kloet, Boudewijn M T Burgering
Mar 6, 2012·Journal of Receptor and Signal Transduction Research·Jun-ichi SakamakiAkiyoshi Fukamizu
Jul 28, 2012·Expert Opinion on Therapeutic Patents·Rubing WangShaoshun Li
Sep 11, 2012·Advances in Pharmacology·Subbarao V Madhunapantula, Gavin P Robertson
Jan 1, 2014·Apoptosis : an International Journal on Programmed Cell Death·K RudolfE Rudolf
Jun 5, 2014·Journal of Molecular Cell Biology·Ahmad Besaratinia, Stella Tommasi
Jun 15, 2014·Journal of Molecular Cell Biology·Lucia Garcia-GuerraIria Nieto-Vázquez
Dec 20, 2014·Cell Death and Differentiation·S ShaliniS Kumar
Mar 23, 2015·Current Treatment Options in Oncology·Douglas B Johnson, Igor Puzanov
Mar 25, 2015·Journal of Molecular Cell Biology·Jason HowittSeong-Seng Tan
May 20, 2015·Cancer Biology & Therapy·Dan ZhangJian-Wei Zhang
Jun 24, 2015·Journal of Molecular Cell Biology·Feng QianJohn W Christman
Jul 4, 2015·Cancer Treatment Reviews·Mirela S PetruleaRomana T Netea-Maier
Jul 29, 2015·Frontiers in Oncology·Maria Libera AsciertoPaolo Antonio Ascierto
Dec 9, 2015·Aging Cell·Rute MartinsWolfgang Link

❮ Previous
Next ❯

Citations

Dec 24, 2018·Drug and Chemical Toxicology·Ramona FigatAgata Skrzypczak
Oct 17, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zeyuan WangChunzhi Zhang
Jun 5, 2018·Chemical & Pharmaceutical Bulletin·Qijing ZhangShaoshun Li
Nov 2, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christin DurchscheinNadine Kretschmer
Sep 20, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yunjuan NieChongyong Guo
Aug 22, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Junbiao WangAugusto Amici
Jul 31, 2021·The Journal of International Medical Research·Shu-Xin MaJia Li
Jan 22, 2020·Journal of Natural Products·Alexander StallingerBeate Rinner
Nov 18, 2020·Current Cancer Drug Targets·Junqi CuiJun Chen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis