Data/hora: 11/06/2024 06:32:12

Provedor de dados: | 48
País: | Chile
Título: | Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC
Autores: | Singh,Thangjam Davis; Meitei,Heikrujam Thoihen; Sharma,Adhikarimayum Lakhikumar; Robinson,Asem; Singh,Lisam Shanjukumar; Singh,Thiyam Ramsing.
Data: | 2015-01-01
Ano: | 2015
Palavras-chave: | Zanthoxylum armatum; Apoptosis; ERK activation; Cisplatin sensitization; DNA damage.
Resumo: | 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 &amp;#947;H2AX 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.
Tipo: | Journal article
Idioma: | Inglês
Identificador: | http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100046
Editor: | Sociedad de Biología de Chile
Formato: | text/html
Fonte: | Biological Research  v.48 2015