Abstract
BackgroundZanthoxylum armatum DC has been an important traditional plant known for its medicinal properties. It is well known for its antimicrobial, larvicidal and cytotoxic activities.MethodsThe potential anticancer effects of the methanol extract and the crude saponins from fruit, bark and leaves of Z. armatum on breast (MDA-MB-468 and MCF-7) and colorectal (Caco-2) cancer cell lines using MTT, neutral red uptake(NRU) and DAPI stain assays were evaluated.ResultsIn MTT assay the methanol extract of fruit (Zf), bark (Zb) and leaves (Zl) of Zanthoxylum armatum, showed significant and dose dependent growth inhibition of MCF-7, MDA MB-468 and Caco-2 cancer cell lines in a dose of 200 μg/ml and above. The saponins (Zf.Sa, Zb.Sa and Zl.Sa) showed significant activity against MDA MB-468 (95, 94.5 and 85.3%) as compared to MCF-7 (79.8, 9.43, 49.08%) and Caco-2 (75.8, 61.8, 68.62%) respectively. The extracts were further tested in more sensitive NRU assay and its was found that Zf extract showed higher cytotoxic activity as compared to Zb and Zl extracts with 100 μg/ml concentration. The breast cancer cell lines showed more sensitivity toward the crude saponins from fruit and bark with maximum inhibition of up to 93.81(±2.32) % with respect to 71.19(± 2.76) of Actinomycin-D. DAPI staining experiment showed that saponins from fruit induced apoptosis mode of cell death in all three types of cell lines while saponins form leaves and bark showed similar results against MDA MB-468 indicated by nuclear fragmentation and chromatin condensation. The effect of saponins from fruit, bark and leaves (Zf.Sa, Zb.Sa and Zl.Sa) against Caco-2 cell lines inhibited the growth of Caco-2 by 53.16 (±3.31) %, 66.43 (± 3.24) and 45.96 (± 10.67) respectively with respect to Actinomycin-D (4 μM) which showed the growth inhibition of 65.40(±4.29) %.ConclusionThe current study clearly demonstrates that the extract and crude saponins from fruit, bark and leaves of traditional medicinal plant Zanthoxyllum armatum DC., has the potential to exert its cytotoxic effect on cancer cell lines isolated form human by a mechanism involving apoptosis. The overall finding demonstrate that this plant specially fruits, could be potential source of new anticancer compounds for possible drug development against cancer.
Highlights
Zanthoxylum armatum DC has been an important traditional plant known for its medicinal properties
Cell lines MCF-7 and MDA-MB-468 cells were purchased from ATCC (American Type Culture Collection, USA) through an authorized distributor, LGC Standards, Teddington, UK
Plant material Five kg of each of leaves, bark and fruit of Z. armatum were collected from Mansehra, Tanawal area of KPK Pakistan in the month of August, 2013
Summary
Zanthoxylum armatum DC has been an important traditional plant known for its medicinal properties. It is well known for its antimicrobial, larvicidal and cytotoxic activities. One of the studies revealed that since 1994 50 % of the drugs approved are originated from natural sources. The drugs approved cover a variety of therapeutic indications, most of these are related to cancer treatment [1]. It is evident from various studies that medicinally important plants including Podophyllum peltatum, Taxus brevifolia, and Cantharanthus roseus and many others provided bioactive compounds including podophyllotoxin, taxol, and vincristine etc. The present study was carried out to explore the anticancer activity of extracts and crude saponin fractions from Zanthoxylum armatum fruit, bark and leaves in cultured human breast cancer cells (MCF-7 and MDA MB-468) and colorectal cancer cell lines (Caco-2)
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