Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC

BACKGROUND: Clinical use of chemotherapeutic drug, cisplatin is limited by its toxicity and drug resistance. Therefore, efforts continue for the discovery of novel combination therapies with cisplatin, to increase efficacy and reduce its toxicity. Here, we screened 16 medicinal plant extracts from N...

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Autores principales:	Singh,Thangjam Davis, Meitei,Heikrujam Thoihen, Sharma,Adhikarimayum Lakhikumar, Robinson,Asem, Singh,Lisam Shanjukumar, Singh,Thiyam Ramsing
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2015
Materias:	Zanthoxylum armatum Apoptosis ERK activation Cisplatin sensitization DNA damage
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100046
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spelling	oai:scielo:S0716-976020150001000462016-02-16Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DCSingh,Thangjam DavisMeitei,Heikrujam ThoihenSharma,Adhikarimayum LakhikumarRobinson,AsemSingh,Lisam ShanjukumarSingh,Thiyam Ramsing Zanthoxylum armatum Apoptosis ERK activation Cisplatin sensitization DNA damage BACKGROUND: Clinical use of chemotherapeutic drug, cisplatin is limited by its toxicity and drug resistance. Therefore, efforts continue for the discovery of novel combination therapies with cisplatin, to increase efficacy and reduce its toxicity. Here, we screened 16 medicinal plant extracts from Northeast part of India and found that leaf extract of Zanthoxylum armatum DC. (ZALE) induced cytotoxicity as well as an effect on the increasing of the efficiency of chemotherapeutic drugs (cisplatin, mitomycin C and camptothecin). This work shows detail molecular mechanism of anti-cancer activity of ZALE and its potential for combined treatment regimens to enhance the apoptotic response of chemotherapeutic drugs. RESULTS: ZALE induced cytotoxicity, nuclear blebbing and DNA fragmentation in HeLA cells suggesting apoptosis induction in human cervical cell line. However, the apoptosis induced was independent of caspase 3 activation and poly ADP ribose polymerase (PARP) cleavage. Further, ZALE activated Mitogen-activated protein kinases (MAPK) pathway as revealed by increased phosphorylation of extracellular-signal-regulated kinases (ERK), p38 and c-Jun N-ter-minal kinase (JNK). Inhibition of ERK activation but not p38 or JNK completely blocked the ZALE induced apoptosis suggesting an ERK dependent apoptosis. Moreover, ZALE generated DNA double strand breaks as suggested by the induction γH2AX foci formation. Interestingly, pretreatment of certain cancer cell lines with ZALE, sensitized the cancer cells to cisplatin and other chemotherapeutic drugs. Enhanced caspase activation was observed in the synergistic interaction among chemotherapeutic drugs and ZALE. CONCLUSION: Purification and identification of the bio-active molecules from the ZALE or as a complementary treatment for a sequential treatment of ZALE with chemotherapeutic drugs might be a new challenger to open a new therapeutic window for the novel anti-cancer treatment.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.48 20152015-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100046en10.1186/S40659-015-003
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Zanthoxylum armatum Apoptosis ERK activation Cisplatin sensitization DNA damage
spellingShingle	Zanthoxylum armatum Apoptosis ERK activation Cisplatin sensitization DNA damage Singh,Thangjam Davis Meitei,Heikrujam Thoihen Sharma,Adhikarimayum Lakhikumar Robinson,Asem Singh,Lisam Shanjukumar Singh,Thiyam Ramsing Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC
description	BACKGROUND: Clinical use of chemotherapeutic drug, cisplatin is limited by its toxicity and drug resistance. Therefore, efforts continue for the discovery of novel combination therapies with cisplatin, to increase efficacy and reduce its toxicity. Here, we screened 16 medicinal plant extracts from Northeast part of India and found that leaf extract of Zanthoxylum armatum DC. (ZALE) induced cytotoxicity as well as an effect on the increasing of the efficiency of chemotherapeutic drugs (cisplatin, mitomycin C and camptothecin). This work shows detail molecular mechanism of anti-cancer activity of ZALE and its potential for combined treatment regimens to enhance the apoptotic response of chemotherapeutic drugs. RESULTS: ZALE induced cytotoxicity, nuclear blebbing and DNA fragmentation in HeLA cells suggesting apoptosis induction in human cervical cell line. However, the apoptosis induced was independent of caspase 3 activation and poly ADP ribose polymerase (PARP) cleavage. Further, ZALE activated Mitogen-activated protein kinases (MAPK) pathway as revealed by increased phosphorylation of extracellular-signal-regulated kinases (ERK), p38 and c-Jun N-ter-minal kinase (JNK). Inhibition of ERK activation but not p38 or JNK completely blocked the ZALE induced apoptosis suggesting an ERK dependent apoptosis. Moreover, ZALE generated DNA double strand breaks as suggested by the induction γH2AX foci formation. Interestingly, pretreatment of certain cancer cell lines with ZALE, sensitized the cancer cells to cisplatin and other chemotherapeutic drugs. Enhanced caspase activation was observed in the synergistic interaction among chemotherapeutic drugs and ZALE. CONCLUSION: Purification and identification of the bio-active molecules from the ZALE or as a complementary treatment for a sequential treatment of ZALE with chemotherapeutic drugs might be a new challenger to open a new therapeutic window for the novel anti-cancer treatment.
author	Singh,Thangjam Davis Meitei,Heikrujam Thoihen Sharma,Adhikarimayum Lakhikumar Robinson,Asem Singh,Lisam Shanjukumar Singh,Thiyam Ramsing
author_facet	Singh,Thangjam Davis Meitei,Heikrujam Thoihen Sharma,Adhikarimayum Lakhikumar Robinson,Asem Singh,Lisam Shanjukumar Singh,Thiyam Ramsing
author_sort	Singh,Thangjam Davis
title	Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC
title_short	Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC
title_full	Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC
title_fullStr	Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC
title_full_unstemmed	Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC
title_sort	anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of zanthoxylum armatum dc
publisher	Sociedad de Biología de Chile
publishDate	2015
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100046
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Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC

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