Antitumor Activity of 3-Indolylmethanamines 31B and PS121912

Margaret L Guthrie; Preetpal S Sidhu; Emily K Hill; Timothy C Horan; Premchendar Nandhikonda; Kelly A Teske; Nina Y Yuan; Marina Sidorko; Revathi Rodali; James M Cook; Lanlan Han; Nicholas R Silvaggi; Daniel D Bikle; Richard G Moore; Rakesh K Singh; Leggy A Arnold

Antitumor Activity of 3-Indolylmethanamines 31B and PS121912

Journal article

Peer reviewed

Antitumor Activity of 3-Indolylmethanamines 31B and PS121912

Margaret L Guthrie, Preetpal S Sidhu, Emily K Hill, Timothy C Horan, Premchendar Nandhikonda, Kelly A Teske, Nina Y Yuan, Marina Sidorko, Revathi Rodali, James M Cook, …

Anticancer research, Vol.35(11), pp.6001-6007

11/2015

PMCID: PMC4633305

PMID: 26504023

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Abstract

To investigate the in vivo effects of 3-indolylmethanamines 31B and PS121912 in treating ovarian cancer and leukemia, respectively. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and western blotting were applied to demonstrate the induction of apoptosis. Xenografted mice were investigated to show the antitumor effects of 3-indolylmethanamines. (13)C-Nuclear magnetic resource (NMR) and western blotting were used to demonstrate inhibition of glucose metabolism. 31B inhibited ovarian cancer cell proliferation and activated caspase-3, cleaved poly (ADP-ribose) polymerase 1 (PARP1), and phosphorylated mitogen-activated protein kinases (MAPK), JUN N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38. 31B reduced ovarian cancer xenograft tumor growth and PS121912 inhibited the growth of HL-60-derived xenografts without any sign of toxicity. Compound 31B inhibited de novo glycolysis and lipogenesis mediated by the reduction of fatty acid synthase and lactate dehydrogenase-A expression. 3-Indolylmethanamines represent a new class of antitumor agents. We have shown for the first time the in vivo anticancer effects of 3-indolylmethanamines 31B and PS121912.

Flow Cytometry

Amines - chemistry

Aniline Compounds - pharmacology

Hydrocarbons, Aromatic - pharmacology

Magnetic Resonance Spectroscopy

Apoptosis - drug effects

Humans

Ovarian Neoplasms - pathology

Blotting, Western

Xenograft Model Antitumor Assays

Animals

Mice, Nude

Female

Indoles - pharmacology

Antineoplastic Agents - pharmacology

Cell Proliferation - drug effects

Mice

Ovarian Neoplasms - metabolism

Tumor Cells, Cultured

Indoles - chemistry

Ovarian Neoplasms - drug therapy

Details

Title: Subtitle: Antitumor Activity of 3-Indolylmethanamines 31B and PS121912
Creators: Margaret L Guthrie - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A
Preetpal S Sidhu - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A
Emily K Hill - Molecular Therapeutics Laboratory, Program in Women's Oncology, Women and Infants' Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI, U.S.A
Timothy C Horan - Molecular Therapeutics Laboratory, Program in Women's Oncology, Women and Infants' Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI, U.S.A
Premchendar Nandhikonda - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A
Kelly A Teske - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A
Nina Y Yuan - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A
Marina Sidorko - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A
Revathi Rodali - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A
James M Cook - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A
Lanlan Han - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A
Nicholas R Silvaggi - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A
Daniel D Bikle - Endocrine Research Unit, Department of Medicine, Veterans Affairs Medical Center, San Francisco, CA, U.S.A
Richard G Moore
Rakesh K Singh - Molecular Therapeutics Laboratory, Program in Women's Oncology, Women and Infants' Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI, U.S.A
Leggy A Arnold - Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, U.S.A. Milwaukee Institute of Drug Discovery, University of Wisconsin, Milwaukee, WI, U.S.A. arnold2@uwm.edu
Resource Type: Journal article
Publication Details: Anticancer research, Vol.35(11), pp.6001-6007
Publisher: Greece
PMID: 26504023
PMCID: PMC4633305
ISSN: 1791-7530
eISSN: 1791-7530
Grant note: R01 MH096463 / NIMH NIH HHS R03 DA031090 / NIDA NIH HHS R01 HL118561 / NHLBI NIH HHS R01 NS076517 / NINDS NIH HHS R01 AR050023 / NIAMS NIH HHS
Language: English
Date published: 11/2015
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983931065702771

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