Effects of two disiloxanes ALIS-409 and ALIS-421 on chemoprevention in model experiments

Harukuni Tokuda, Takashi Maoka, Nobutaka Suzuiki, J. Hohmann, A. Vasas, Helga Engi, I. Mucsi, Ulrike Olszewski, Gerhard Hamilton, Leonard Amaral, J. Molnár

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Morpholino-disiloxane (ALIS-409) and piperazino-disiloxane (ALIS-421) compounds were developed as inhibitors of multidrug resistance of various types of cancer cells. In the present study, the effects of ALIS-409 and ALIS-421 compounds were investigated on cancer promotion and on co-existence of tumor and normal cells. The two compounds were evaluated for their inhibitory effects on Epstein-Barr virus immediate-early antigen (EBV-EA) expression induced by tetradecanoyl-phorbol-acetate (TPA) in Raji cell cultures. The method is known as a primary screening test for antitumor effect, below the (IC50) concentration. ALIS-409 was more effective in inhibiting EBV-EA (100 μg/ml) and tumor promotion, than ALIS-421, in the concentration range up to 1000 μg/ml. However, neither of the compounds were able to reduce tumor promotion significantly, expressed as inhibition of TPA-induced tumor antigen activation. Based on the in vitro results, the two disiloxanes were investigated in vivo for their effects on mouse skin tumors in a two-stage mouse skin carcinogenesis study. The application of dimethyl-benzanthracene (DMBA; 390 nmol) as a tumor initiator was followed by exposure to TPA (1.7 nmol/l) as a tumor promoter. The experiments showed that ALIS-409 at a concentration of 85 nmol/l had a weak EBV-EA inhibitory effect in vitro and a moderate antitumor activity, compared to the positive control of DMBA plus TPA-treated mice. Flow cytometry by differential staining demonstrated interactions in co-cultures of MCF7 breast cancer and MRC5 human lung fibroblasts. The growth rate of tumor cells in mixed populations of MCF7 breast cancer and MRC5 normal fibroblast cells was reduced in the presence of ALIS-409, as compared to the control non-treated cell populations. The two disiloxanes were moderately-effective in chemoprevention in DMBA-induced and TPA-promoted in vivo tumor formation. Authors suggest that the inhibition of tumor cell and fibroblast interaction by ALIS409 might have some perspective in the development of anti-stromal therapy.

Original languageEnglish
Pages (from-to)2021-2027
Number of pages7
JournalAnticancer Research
Volume33
Issue number5
Publication statusPublished - May 2013

Fingerprint

Chemoprevention
Acetates
Neoplasms
9,10-Dimethyl-1,2-benzanthracene
Fibroblasts
Carcinogens
Breast Neoplasms
1,3-dimethyl-1,3-p-fluorophenyl-1,3-(3-morpholinopropyl)-1,3-disiloxane
disiloxane
1,3-dimethyl-1,3-(4-fluorophenyl)-1,3-(3-butyl-(1-piperazinyl)propyl)-1,3-disiloxane
Morpholinos
Skin
Multiple Drug Resistance
Neoplasm Antigens
Coculture Techniques
Cell Communication
Population
Inhibitory Concentration 50
Flow Cytometry
Carcinogenesis

Keywords

  • Anti-promotion
  • Chemoprevention
  • Coexistence of tumor and normal cells
  • Disiloxanes
  • EBV-induced early antigen
  • Two-stage mouse skin carcinogenesis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effects of two disiloxanes ALIS-409 and ALIS-421 on chemoprevention in model experiments. / Tokuda, Harukuni; Maoka, Takashi; Suzuiki, Nobutaka; Hohmann, J.; Vasas, A.; Engi, Helga; Mucsi, I.; Olszewski, Ulrike; Hamilton, Gerhard; Amaral, Leonard; Molnár, J.

In: Anticancer Research, Vol. 33, No. 5, 05.2013, p. 2021-2027.

Research output: Contribution to journalArticle

Tokuda, H, Maoka, T, Suzuiki, N, Hohmann, J, Vasas, A, Engi, H, Mucsi, I, Olszewski, U, Hamilton, G, Amaral, L & Molnár, J 2013, 'Effects of two disiloxanes ALIS-409 and ALIS-421 on chemoprevention in model experiments', Anticancer Research, vol. 33, no. 5, pp. 2021-2027.
Tokuda, Harukuni ; Maoka, Takashi ; Suzuiki, Nobutaka ; Hohmann, J. ; Vasas, A. ; Engi, Helga ; Mucsi, I. ; Olszewski, Ulrike ; Hamilton, Gerhard ; Amaral, Leonard ; Molnár, J. / Effects of two disiloxanes ALIS-409 and ALIS-421 on chemoprevention in model experiments. In: Anticancer Research. 2013 ; Vol. 33, No. 5. pp. 2021-2027.
@article{f1441d0a765840de9a73df7eedaae6c7,
title = "Effects of two disiloxanes ALIS-409 and ALIS-421 on chemoprevention in model experiments",
abstract = "Morpholino-disiloxane (ALIS-409) and piperazino-disiloxane (ALIS-421) compounds were developed as inhibitors of multidrug resistance of various types of cancer cells. In the present study, the effects of ALIS-409 and ALIS-421 compounds were investigated on cancer promotion and on co-existence of tumor and normal cells. The two compounds were evaluated for their inhibitory effects on Epstein-Barr virus immediate-early antigen (EBV-EA) expression induced by tetradecanoyl-phorbol-acetate (TPA) in Raji cell cultures. The method is known as a primary screening test for antitumor effect, below the (IC50) concentration. ALIS-409 was more effective in inhibiting EBV-EA (100 μg/ml) and tumor promotion, than ALIS-421, in the concentration range up to 1000 μg/ml. However, neither of the compounds were able to reduce tumor promotion significantly, expressed as inhibition of TPA-induced tumor antigen activation. Based on the in vitro results, the two disiloxanes were investigated in vivo for their effects on mouse skin tumors in a two-stage mouse skin carcinogenesis study. The application of dimethyl-benzanthracene (DMBA; 390 nmol) as a tumor initiator was followed by exposure to TPA (1.7 nmol/l) as a tumor promoter. The experiments showed that ALIS-409 at a concentration of 85 nmol/l had a weak EBV-EA inhibitory effect in vitro and a moderate antitumor activity, compared to the positive control of DMBA plus TPA-treated mice. Flow cytometry by differential staining demonstrated interactions in co-cultures of MCF7 breast cancer and MRC5 human lung fibroblasts. The growth rate of tumor cells in mixed populations of MCF7 breast cancer and MRC5 normal fibroblast cells was reduced in the presence of ALIS-409, as compared to the control non-treated cell populations. The two disiloxanes were moderately-effective in chemoprevention in DMBA-induced and TPA-promoted in vivo tumor formation. Authors suggest that the inhibition of tumor cell and fibroblast interaction by ALIS409 might have some perspective in the development of anti-stromal therapy.",
keywords = "Anti-promotion, Chemoprevention, Coexistence of tumor and normal cells, Disiloxanes, EBV-induced early antigen, Two-stage mouse skin carcinogenesis",
author = "Harukuni Tokuda and Takashi Maoka and Nobutaka Suzuiki and J. Hohmann and A. Vasas and Helga Engi and I. Mucsi and Ulrike Olszewski and Gerhard Hamilton and Leonard Amaral and J. Moln{\'a}r",
year = "2013",
month = "5",
language = "English",
volume = "33",
pages = "2021--2027",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "5",

}

TY - JOUR

T1 - Effects of two disiloxanes ALIS-409 and ALIS-421 on chemoprevention in model experiments

AU - Tokuda, Harukuni

AU - Maoka, Takashi

AU - Suzuiki, Nobutaka

AU - Hohmann, J.

AU - Vasas, A.

AU - Engi, Helga

AU - Mucsi, I.

AU - Olszewski, Ulrike

AU - Hamilton, Gerhard

AU - Amaral, Leonard

AU - Molnár, J.

PY - 2013/5

Y1 - 2013/5

N2 - Morpholino-disiloxane (ALIS-409) and piperazino-disiloxane (ALIS-421) compounds were developed as inhibitors of multidrug resistance of various types of cancer cells. In the present study, the effects of ALIS-409 and ALIS-421 compounds were investigated on cancer promotion and on co-existence of tumor and normal cells. The two compounds were evaluated for their inhibitory effects on Epstein-Barr virus immediate-early antigen (EBV-EA) expression induced by tetradecanoyl-phorbol-acetate (TPA) in Raji cell cultures. The method is known as a primary screening test for antitumor effect, below the (IC50) concentration. ALIS-409 was more effective in inhibiting EBV-EA (100 μg/ml) and tumor promotion, than ALIS-421, in the concentration range up to 1000 μg/ml. However, neither of the compounds were able to reduce tumor promotion significantly, expressed as inhibition of TPA-induced tumor antigen activation. Based on the in vitro results, the two disiloxanes were investigated in vivo for their effects on mouse skin tumors in a two-stage mouse skin carcinogenesis study. The application of dimethyl-benzanthracene (DMBA; 390 nmol) as a tumor initiator was followed by exposure to TPA (1.7 nmol/l) as a tumor promoter. The experiments showed that ALIS-409 at a concentration of 85 nmol/l had a weak EBV-EA inhibitory effect in vitro and a moderate antitumor activity, compared to the positive control of DMBA plus TPA-treated mice. Flow cytometry by differential staining demonstrated interactions in co-cultures of MCF7 breast cancer and MRC5 human lung fibroblasts. The growth rate of tumor cells in mixed populations of MCF7 breast cancer and MRC5 normal fibroblast cells was reduced in the presence of ALIS-409, as compared to the control non-treated cell populations. The two disiloxanes were moderately-effective in chemoprevention in DMBA-induced and TPA-promoted in vivo tumor formation. Authors suggest that the inhibition of tumor cell and fibroblast interaction by ALIS409 might have some perspective in the development of anti-stromal therapy.

AB - Morpholino-disiloxane (ALIS-409) and piperazino-disiloxane (ALIS-421) compounds were developed as inhibitors of multidrug resistance of various types of cancer cells. In the present study, the effects of ALIS-409 and ALIS-421 compounds were investigated on cancer promotion and on co-existence of tumor and normal cells. The two compounds were evaluated for their inhibitory effects on Epstein-Barr virus immediate-early antigen (EBV-EA) expression induced by tetradecanoyl-phorbol-acetate (TPA) in Raji cell cultures. The method is known as a primary screening test for antitumor effect, below the (IC50) concentration. ALIS-409 was more effective in inhibiting EBV-EA (100 μg/ml) and tumor promotion, than ALIS-421, in the concentration range up to 1000 μg/ml. However, neither of the compounds were able to reduce tumor promotion significantly, expressed as inhibition of TPA-induced tumor antigen activation. Based on the in vitro results, the two disiloxanes were investigated in vivo for their effects on mouse skin tumors in a two-stage mouse skin carcinogenesis study. The application of dimethyl-benzanthracene (DMBA; 390 nmol) as a tumor initiator was followed by exposure to TPA (1.7 nmol/l) as a tumor promoter. The experiments showed that ALIS-409 at a concentration of 85 nmol/l had a weak EBV-EA inhibitory effect in vitro and a moderate antitumor activity, compared to the positive control of DMBA plus TPA-treated mice. Flow cytometry by differential staining demonstrated interactions in co-cultures of MCF7 breast cancer and MRC5 human lung fibroblasts. The growth rate of tumor cells in mixed populations of MCF7 breast cancer and MRC5 normal fibroblast cells was reduced in the presence of ALIS-409, as compared to the control non-treated cell populations. The two disiloxanes were moderately-effective in chemoprevention in DMBA-induced and TPA-promoted in vivo tumor formation. Authors suggest that the inhibition of tumor cell and fibroblast interaction by ALIS409 might have some perspective in the development of anti-stromal therapy.

KW - Anti-promotion

KW - Chemoprevention

KW - Coexistence of tumor and normal cells

KW - Disiloxanes

KW - EBV-induced early antigen

KW - Two-stage mouse skin carcinogenesis

UR - http://www.scopus.com/inward/record.url?scp=84878192637&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878192637&partnerID=8YFLogxK

M3 - Article

C2 - 23645751

AN - SCOPUS:84878192637

VL - 33

SP - 2021

EP - 2027

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 5

ER -