Gap junction enhancer increases efficacy of cisplatin to attenuate mammary tumor growth

Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors. Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines (PQs) acts as gap junction enhancer, ability to inc...

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Published in:PloS one 2012-09, Vol.7 (9), p.e44963-e44963
Main Authors: Shishido, Stephanie N, Nguyen, Thu A
Format: Article
Language:English
Subjects:
17β-Estradiol
Animal models
Animals
Antineoplastic Agents - pharmacology
Antineoplastic drugs
Apoptosis
Biology
Breast cancer
Cancer
Caspase
Caspase-3
Cell culture
Cell cycle
Cell Line, Tumor
Cell Proliferation - drug effects
Cell signaling
Cisplatin
Cisplatin - pharmacology
Communication
Connexin 43
Connexins
Cytotoxicity
Deoxyribonucleic acid
DNA
Drug dosages
Drug therapy
Drugs
Effectiveness
Estrogens
Fibroblasts
Gallbladder
Gangrene
Gap junctions
Gap Junctions - drug effects
Gap Junctions - metabolism
Growth
Homeostasis
Humans
Kinases
Laboratory animals
Mammary gland
Mammary Neoplasms, Experimental - metabolism
Mammary Neoplasms, Experimental - pathology
Medical research
Medicine
Metastasis
Mice
Mice, Nude
Organic compounds
Ovarian cancer
Proteins
Quinolines
Sex hormones
Signal transduction
Tissues
Tumor cells
Tumors
Veterinary medicine
Xenograft Model Antitumor Assays
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Nguyen, Thu A
description Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors. Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines (PQs) acts as gap junction enhancer, ability to increase the gap junctional intercellular communication, in breast cancer cells. We examined the effect of combinational treatment of PQs and antineoplastic drugs in an animal model, showing an increase in efficacy of antineoplastic drugs via the enhancement of gap junctions. Mice were implanted with estradiol-17ß (1.7 mg/pellet) before the injection of 1×10⁷ T47D breast cancer cells subcutaneously into the inguinal region of mammary fat pad. Animals were treated intraperitoneally with DMSO (control), cisplatin (3.5 mg/kg), PQ (25 mg/kg), or a combining treatment of cisplatin and PQ. Cisplatin alone decreased mammary tumor growth by 85% while combinational treatment of cisplatin and PQ1 or PQ7 showed an additional reduction of 77% and 22% of tumor growth after 7 treatments at every 2 days, respectively. Histological results showed a significant increase of gap junction proteins, Cx43 and Cx26, in PQ-treated tissues compared to control or cisplatin. Furthermore, evidence of highly stained caspase 3 in tumors of combinational treatment (PQ and cisplatin) was seen compared to cisplatin alone. We have showed for the first time an increase in the efficacy of antineoplastic drugs through a combinational treatment with PQs, a specific class of gap junction enhancers.
doi_str_mv 10.1371/journal.pone.0044963
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Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines (PQs) acts as gap junction enhancer, ability to increase the gap junctional intercellular communication, in breast cancer cells. We examined the effect of combinational treatment of PQs and antineoplastic drugs in an animal model, showing an increase in efficacy of antineoplastic drugs via the enhancement of gap junctions. Mice were implanted with estradiol-17ß (1.7 mg/pellet) before the injection of 1×10⁷ T47D breast cancer cells subcutaneously into the inguinal region of mammary fat pad. Animals were treated intraperitoneally with DMSO (control), cisplatin (3.5 mg/kg), PQ (25 mg/kg), or a combining treatment of cisplatin and PQ. 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1932-6203
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source Publicly Available Content Database; PubMed Central
subjects 17β-Estradiol
Animal models
Animals
Antineoplastic Agents - pharmacology
Antineoplastic drugs
Apoptosis
Biology
Breast cancer
Cancer
Caspase
Caspase-3
Cell culture
Cell cycle
Cell Line, Tumor
Cell Proliferation - drug effects
Cell signaling
Cisplatin
Cisplatin - pharmacology
Communication
Connexin 43
Connexins
Cytotoxicity
Deoxyribonucleic acid
DNA
Drug dosages
Drug therapy
Drugs
Effectiveness
Estrogens
Fibroblasts
Gallbladder
Gangrene
Gap junctions
Gap Junctions - drug effects
Gap Junctions - metabolism
Growth
Homeostasis
Humans
Kinases
Laboratory animals
Mammary gland
Mammary Neoplasms, Experimental - metabolism
Mammary Neoplasms, Experimental - pathology
Medical research
Medicine
Metastasis
Mice
Mice, Nude
Organic compounds
Ovarian cancer
Proteins
Quinolines
Sex hormones
Signal transduction
Tissues
Tumor cells
Tumors
Veterinary medicine
Xenograft Model Antitumor Assays
title Gap junction enhancer increases efficacy of cisplatin to attenuate mammary tumor growth
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T15%3A06%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Gap%20junction%20enhancer%20increases%20efficacy%20of%20cisplatin%20to%20attenuate%20mammary%20tumor%20growth&rft.jtitle=PloS%20one&rft.au=Shishido,%20Stephanie%20N&rft.date=2012-09-13&rft.volume=7&rft.issue=9&rft.spage=e44963&rft.epage=e44963&rft.pages=e44963-e44963&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0044963&rft_dat=%3Cgale_plos_%3EA543317656%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c758t-5e2719049c6b9e50a5614928e3199418d503938ed7288c4a2efdc618d0e2c1663%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1326544719&rft_id=info:pmid/23028705&rft_galeid=A543317656&rfr_iscdi=true