Abstract：
:Tumor angiogenesis and PI3K/Akt/mTOR pathway are two major molecular objectives for the treatment and management of breast cancer. Here we first time report the molecular mechanism of a marine sponge alkaloid derivative 4-chloro fascapysin (4-CF) for its anticancer and antiangiogenesis potential. It simultaneously targets multiple cancer and angiogenesis dynamics, such as proliferation, chemotaxis cell migration, and invasion, growth factors signaling cascade, autophagy and apoptosis in HUVEC and MDAMB-231 breast cancer cells. It inhibited the VEGF mediated microvessel sprouting and blood vessel formation in the matrigel plug of C57/BL6J mice. It inhibits the tumor growth in ET (solid) mouse tumor model. It significantly inhibited cell survival through PI3K/Akt/mTOR pathway, with attendant effects on key pro-angiogenesis factors like HIF-1α, eNOS and MMP-2/9. The cytotoxicity of 4-CF was reversed by co-treatment with the VEGF and Akt inhibitors sunitinib and perifosine, respectively or by the addition of neutralizing VEGF antibodies. The apoptotic potential of 4-CF was through mitochondrial dependent as illustrated through loss of mitochondrial membrane potential. The safety profile of 4-CF was acceptable as it exhibits five times high cytotoxic IC50 value in normal cells as well as no apparent toxicities in experimental tumor mice at therapeutic doses.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Sharma S,Guru SK,Manda S,Kumar A,Mintoo MJ,Prasad VD,Sharma PR,Mondhe DM,Bharate SB,Bhushan Sdoi
10.1016/j.cbi.2017.07.017subject
Has Abstractpub_date
2017-09-25 00:00:00pages
47-60eissn
0009-2797issn
1872-7786pii
S0009-2797(17)30265-Xjournal_volume
275pub_type
杂志文章abstract：:Recombinant (r) and native butyrylcholinesterse (BChE) are potent bioscavengers of organophosphates (OPs) such as nerve agents and pesticides and are undergoing development as antidotal treatments for OP-induced toxicity. Because of the lethal properties of such agents, regulatory approval will require extensive testi...
journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(90)90072-u
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
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journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(82)90024-2
更新日期：1982-05-01 00:00:00
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journal_title：Chemico-biological interactions
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doi：10.1016/j.cbi.2017.06.007
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(78)90090-x
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.05.002
更新日期：2008-09-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2013.09.007
更新日期：2013-11-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(76)90023-5
更新日期：1976-07-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(99)00139-8
更新日期：2000-01-03 00:00:00
abstract：:Arthritis is one of the most prevalent chronic inflammatory diseases, and it is characterized by structural and biochemical changes in major tissues of the joint, including degradation of the cartilage matrix, insufficient synthesis of extracellular matrix (ECM). Ecklonia cava (EC) is a member of the family of Laminar...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2009.01.006
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.11.010
更新日期：2016-12-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.06.006
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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doi：10.1016/j.cbi.2005.10.104
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.06.023
更新日期：2019-08-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.04.001
更新日期：2008-09-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.01.011
更新日期：2016-03-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(99)00161-1
更新日期：2000-03-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/j.cbi.2006.06.007
更新日期：2006-10-27 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 评论,信件
doi：10.1016/j.cbi.2014.10.010
更新日期：2014-10-05 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(77)90128-4
更新日期：1977-02-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.03.016
更新日期：2016-11-25 00:00:00
abstract：:A novel post-addition method, based on the trapping of ABTS-radicals, is applied for studying the total antioxidant capacity of seminal plasma. A remarkable profile is observed, in which seminal plasma quenches radicals in a continuous, relatively slow fashion. Five putative antioxidants present in seminal plasma were...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(00)00179-4
更新日期：2000-07-03 00:00:00
