PMID- 27798863
OWN - NLM
STAT- MEDLINE
DCOM- 20170127
LR  - 20181113
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 36
IP  - 10
DP  - 2016 Oct
TI  - Substituted Tetrahydroisoquinolines as Microtubule-destabilizing Agents in Triple 
      Negative Human Breast Cancer Cells.
PG  - 5043-5052
AB  - Triple-negative breast cancer (TNBC) occurs at greater frequency amongst 
      African-Americans, being characterized by the absence of estrogen receptor (ER), 
      progesterone receptor (PR) and human epidermal receptor 2 (HER2). TNBC is often 
      invasive and typically treated with cytostatic agents such as taxanes in 
      combination with anthracyclines or platinum-based drugs. In this study, we 
      synthesized a number of tetrahydroisoquinoline moieties by N-amination of 
      substituted isoquinolines by O-mesytelene sulfonylhydroxylamine followed by ylide 
      formation and reduction, which yielded the desired, substituted 
      tetrahydroisoquinolines (THIQs) in moderate to good yield. Using a differential 
      scatter plot to identify potential selective ER-modulating drugs in ER-positive 
      control cells (MCF-7) driven by estradiol vs. TNBC (MDA-MB-231) cells, the in 
      vitro data showed an absence of effects on the ER (compared to 4-hydroxytamoxifen 
      and raloxifene). In contrast, two lead compounds halted proliferation 
      (cytostatic) in MDA-MB-231 TNBC cells at a potency level below 2.5 muM concomitant 
      with mitotic arrest, attenuated replicative DNA synthesis, halted microtubule 
      nucleation/stunted tubulin polymerization, abnormal expansive cytoskeletal 
      tubulin and actin morphologies with multinucleation of cells. The most effective 
      cytostatic compounds GM-4-53 and GM-3-121 blocked replicative processes at the 
      G(2) growth phase. These findings suggest that specific THIQs work independently 
      of the ER, by holding static the microtubule network thereby preventing mitosis. 
      Future work is required to establish the safety and efficacy of these drugs and 
      their potential adjunct therapeutic gain in the presence of taxanes in TNBC.
CI  - Copyright(c) 2016 International Institute of Anticancer Research (Dr. John G. 
      Delinassios), All rights reserved.
FAU - Gangapuram, Madhavi
AU  - Gangapuram M
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, U.S.A.
FAU - Jean, Riccardo
AU  - Jean R
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, U.S.A.
FAU - Mazzio, Elizabeth
AU  - Mazzio E
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, U.S.A.
FAU - Badisa, Ramesh
AU  - Badisa R
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, U.S.A.
FAU - Eyunni, Suresh
AU  - Eyunni S
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, U.S.A.
FAU - Goodman, Carl B
AU  - Goodman CB
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, U.S.A.
FAU - Redda, Kinfe K
AU  - Redda KK
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, U.S.A.
FAU - Soliman, Karam F
AU  - Soliman KF
AD  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 
      Tallahassee, FL, U.S.A. karam.soliman@famu.edu.
LA  - eng
GR  - G12 MD007582/MD/NIMHD NIH HHS/United States
GR  - P20 MD006738/MD/NIMHD NIH HHS/United States
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Tetrahydroisoquinolines)
RN  - 0 (Tubulin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Humans
MH  - Microtubules/*drug effects
MH  - Polymerization/drug effects
MH  - Tetrahydroisoquinolines/*pharmacology
MH  - Triple Negative Breast Neoplasms/drug therapy
MH  - Tubulin/metabolism
PMC - PMC5104193
MID - NIHMS817533
OTO - NOTNLM
OT  - Triple-negative breast cancer
OT  - taxanes
OT  - tetrahydroisoquinolines
EDAT- 2016/11/01 06:00
MHDA- 2017/01/28 06:00
PMCR- 2016/11/10
CRDT- 2016/11/01 06:00
PHST- 2016/08/18 00:00 [received]
PHST- 2016/09/12 00:00 [accepted]
PHST- 2016/11/01 06:00 [pubmed]
PHST- 2017/01/28 06:00 [medline]
PHST- 2016/11/01 06:00 [entrez]
PHST- 2016/11/10 00:00 [pmc-release]
AID - 36/10/5043 [pii]
AID - 10.21873/anticanres.11073 [doi]
PST - ppublish
SO  - Anticancer Res. 2016 Oct;36(10):5043-5052. doi: 10.21873/anticanres.11073.