PMID- 28233466
OWN - NLM
STAT- MEDLINE
DCOM- 20180131
LR  - 20231112
IS  - 2192-2659 (Electronic)
IS  - 2192-2640 (Print)
IS  - 2192-2640 (Linking)
VI  - 6
IP  - 15
DP  - 2017 Aug
TI  - Selectively Inducing Cancer Cell Death by Intracellular Enzyme-Instructed 
      Self-Assembly (EISA) of Dipeptide Derivatives.
LID - 10.1002/adhm.201601400 [doi]
AB  - Tight ligand-receptor binding, paradoxically, is a major root of drug resistance 
      in cancer chemotherapy. To address this problem, instead of using conventional 
      inhibitors or ligands, this paper focuses on the development of a novel 
      process-enzyme-instructed self-assembly (EISA)-to kill cancer cells selectively. 
      Here it is demonstrated that EISA as an intracellular process to generate 
      nanofibrils of short peptides for selectively inhibiting cancer cell 
      proliferation, including drug resistant ones. As the process that turns the 
      non-self-assembling precursors into the self-assembling peptides upon the 
      catalysis of carboxylesterases (CES), EISA occurs intracellularly to selectively 
      inhibit a range of cancer cells that exhibit relatively high CES activities. More 
      importantly, EISA inhibits drug resistant cancer cells (e.g., triple negative 
      breast cancer cells (HCC1937) and platinum-resistant ovarian cells (SKOV3, 
      A2780cis)). With the IC(50) values of 28-80 and 25-44 microg mL(-1) of l- and 
      d-dipeptide precursors against cancer cells, respectively, EISA is innocuous to 
      normal cells. Moreover, using coculture of cancer and normal cells, the 
      selectivity of EISA is validated against cancer cells. Besides revealing that 
      intracellular EISA cause apoptosis or necroptosis to kill the cancer cells, this 
      work illustrates a new approach to amplify the enzymatic difference between 
      cancer and normal cells and to expand the pool of drug candidates for potentially 
      overcoming drug resistance in cancer therapy.
CI  - (c) 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Li, Jie
AU  - Li J
AD  - Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA, 
      02454, USA.
FAU - Shi, Junfeng
AU  - Shi J
AD  - Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA, 
      02454, USA.
FAU - Medina, Jamie E
AU  - Medina JE
AD  - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, 02115, USA.
FAU - Zhou, Jie
AU  - Zhou J
AD  - Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA, 
      02454, USA.
FAU - Du, Xuewen
AU  - Du X
AD  - Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA, 
      02454, USA.
FAU - Wang, Huaimin
AU  - Wang H
AD  - Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA, 
      02454, USA.
AD  - State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, 
      Nankai University, Tianjin, 300071, China.
FAU - Yang, Cuihong
AU  - Yang C
AD  - Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 
      300192, China.
FAU - Liu, Jianfeng
AU  - Liu J
AD  - Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 
      300192, China.
FAU - Yang, Zhimou
AU  - Yang Z
AD  - State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, 
      Nankai University, Tianjin, 300071, China.
FAU - Dinulescu, Daniela M
AU  - Dinulescu DM
AD  - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, 02115, USA.
FAU - Xu, Bing
AU  - Xu B
AD  - Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA, 
      02454, USA.
LA  - eng
GR  - R01 CA142746/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20170224
PL  - Germany
TA  - Adv Healthc Mater
JT  - Advanced healthcare materials
JID - 101581613
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Dipeptides)
RN  - EC 3.1.1.- (Carboxylic Ester Hydrolases)
SB  - IM
MH  - Antineoplastic Agents/administration & dosage
MH  - Apoptosis/*drug effects
MH  - Carboxylic Ester Hydrolases/*metabolism
MH  - Cell Line, Tumor
MH  - Dipeptides/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Neoplasms, Experimental/*drug therapy/*metabolism/pathology
MH  - Treatment Outcome
PMC - PMC5550337
MID - NIHMS872859
OTO - NOTNLM
OT  - anticancer
OT  - drug-resistance
OT  - enzyme
OT  - selectivity
OT  - self-assembly
EDAT- 2017/02/25 06:00
MHDA- 2018/02/01 06:00
PMCR- 2018/08/01
CRDT- 2017/02/25 06:00
PHST- 2016/12/07 00:00 [received]
PHST- 2017/01/16 00:00 [revised]
PHST- 2017/02/25 06:00 [pubmed]
PHST- 2018/02/01 06:00 [medline]
PHST- 2017/02/25 06:00 [entrez]
PHST- 2018/08/01 00:00 [pmc-release]
AID - 10.1002/adhm.201601400 [doi]
PST - ppublish
SO  - Adv Healthc Mater. 2017 Aug;6(15):10.1002/adhm.201601400. doi: 
      10.1002/adhm.201601400. Epub 2017 Feb 24.