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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Isolation and characterization of three new anti-proliferative Sesquiterpenes from Polygonum barbatum and their mechanism via apoptotic pathway

Authors: Umar Farooq, Sadia Naz, Binte Zehra, Ajmal Khan, Syed Abid Ali, Ayaz Ahmed, Rizwana Sarwar, Syed Majid Bukhari, Abdur Rauf, Izhar Ahmad, Yahia Nasser Mabkhot

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

The emergence of chemoresistant cancers and toxicity related to existing chemotherapeutic agents, demand the search for new pharmacophore with enhanced anti-cancer activity and least toxicity. For this purpose, three new sesquiterpenes were isolated from ethyl acetate fraction of the aerial parts of the plant Polygonum barbatum and evaluated for their anti-cancer potential.

Methods

The structural elucidation and characterization of the isolated compounds 1–3 were performed using various spectroscopic techniques such as mass, UV, IR, and extensive 1D/2D–NMR spectroscopy. Furthermore, the compounds 1–3 were subjected to screening of anti-cancer activity against different cell lines followed by brief analysis of apoptotic and anti-angiogenic potentials of the potent hit against non-small cell lung carcinoma cell line.

Results

All the compounds 1–3 were subjected to anti-proliferative potential against non-small cell lung carcinoma (NCI-H460), breast cancer (MCF-7), cervical cancer (HeLa) and normal mouse fibroblast (NIH-3 T3) cell lines. Among these, compound 3 was found to be more cytotoxic against NCI-H460 and MCF-7 cells (IC50 = 17.86 ± 0.72 and 11.86 ± 0.46 μM respectively). When compared with the standard drug cisplatin compound 3 was found to have more potent activity against NCI-H460 (IC50 = 19 ± 1.24 μM) as compared to MCF-7 cell lines (IC50 = 9.62 ± 0.5 μM). Compound 3 induced apoptosis in NCI-H460 cells in a dose dependent manner. It significantly downregulated, the expression of anti-apoptotic (BCL-2 L1 and p53) and increased the expression of pro-apoptotic (BAK and BAX) genes. Besides apoptosis, it also significantly reduced the cell migration and downregulated the angiogenic genes (i.e. VEGF and COX-2), thereby, inhibiting angiogenesis in NCI-H460 cells.

Conclusion

Compound 3 possesses potent anti-proliferative potential as well as induced apoptosis and inhibited the cell migration of the cancerous cells by altering the gene expression, responsible for it.
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Metadata
Title
Isolation and characterization of three new anti-proliferative Sesquiterpenes from Polygonum barbatum and their mechanism via apoptotic pathway
Authors
Umar Farooq
Sadia Naz
Binte Zehra
Ajmal Khan
Syed Abid Ali
Ayaz Ahmed
Rizwana Sarwar
Syed Majid Bukhari
Abdur Rauf
Izhar Ahmad
Yahia Nasser Mabkhot
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3667-9

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