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

Abstract

BackgroundClinical 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 Zanthoxylumarmatum 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.ResultsZALE 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-terminal 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.ConclusionPurification 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s40659-015-0037-4) contains supplementary material, which is available to authorized users.

Compostos químicos isolados de extratos e óleos essenciais do gênero Zanthoxylum Linnaeus (Rutaceae) e seu potencial antimicrobiano

“…Vários estudos etnobotânicos documentaram os diferentes usos etnomedicinais dos extratos e infusões obtidos das cascas, sementes e frutos de Z. alatum no tratamento de diferentes tipos de doenças. Na Índia, onde é conhecido por mukthrubi, é utilizado na preparação de medicamentos indígenas contra várias doenças como asma, bronquite, indigestão, veias varicosas, diarreia , reumatismo, dispepsia e cólera (Singh et al 2015, Nooreen et al 2017. No Nepal é usado contra dor de dente, diabetes, problemas estomacais (Balami, 2006), intoxicação alimentar (Malla et al 2014) e tuberculose (Subedi 2017).…”

An Overview of Genus Zanthoxylum with Special Reference to Its Herbal Significance and Application

“…Z. armatum dried An Overview of Genus Zanthoxylum with Special Reference to Its Herbal Significance… DOI: http://dx.doi.org /10.5772/intechopen.92459 root ethyl acetate extract (EAE) (a good antioxidant) and its two components flavonoids, apigenin and kaempferol-7-O-glucoside, also possess an anticancerous trait against A-549, MIA-PaCa, MCF-7, and CACO 2 cancer colon cell lines [40]. In an extensive study, the ME of leaf of Z. armatum induced apoptosis in cervical cancer cell lines (HeLA) at IC 50 (60 μg/mL) through Caspase 3-independent and extracellular signal-regulated kinases (ERK)-dependent mitogenactivated protein kinases (MAPK) apoptosis pathways [41]. Karmakar et al [42] demonstrated that at an IC 50 value of 102.30 μg/mL, the ME of the leaves of Z. armatum exhibited toxicity against Ehrlich Ascites cancer cells.…”

A review on effective utilization, phytochemical compounds, pharmacological intervention of a popularly used plant for developing a new drug: Zanthoxylum armatum with reference to its anticancer activity

“…Zanthoxyllum armatum leaf extract have the potential effect on increasing the efficiency of chemotherapeutic drugs like camptothecin, mitomycin C and cisplatin. 34 In this study, HeLa cells with 80µg/ml was treated with ZALE for almost 48 hours. It shows morphological changes and cytotoxicity in dose dependent manner.…”