Anti-migratory effects of Piper betle leaf aqueous extract on cancer cells and its microtubule targeting properties
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Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) ISSN 1673-1581 (Print); ISSN 1862-1783 (Online) www.jzus.zju.edu.cn; www.springerlink.com E-mail: [email protected]
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Anti-migratory effects of Piper betle leaf aqueous extract on cancer cells and its microtubule targeting properties*# Mee Lee LOOI†1, Alwyn Khai Howe WONG2, Shelly Anne GNAPRAGASAN2, Anis Zafirah JAPRI2, Aiysvariyah RAJEDADRAM2, Kar Yong PIN3 1
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia 2 School of Biosciences, Taylor’s University, Lakeside Campus, Subang Jaya, Selangor Darul Ehsan 47500, Malaysia 3 Forest Research Institute Malaysia, Kepong, Selangor Darul Ehsan 52109, Malaysia † E-mail: [email protected] https://doi.org/10.1631/jzus.B2000278
Piper betle (PB), also known as “betel” in Malay language, is a tropical Asian vine. PB leaves are commonly chewed by Asians along with betel quid. It contains phenols such as eugenol and hydroxychavicol along with chlorophyll, β-carotene, and vitamin C (Salehi et al., 2019). Extracts from PB leaves have various medicinal properties including anticancer, antioxidant, anti-inflammatory, and antibacterial effects (Salehi et al., 2019). Previous research has shown that PB induces cell cycle arrest at late S or G2/M phase and causes apoptosis at higher doses (Wu et al., 2014; Guha Majumdar and Subramanian, 2019). A combination of PB leaf extract has also been shown to enhance the cytotoxicity of the anticancer drug, 5-fluorouracil (5-FU), in cancer cells (Ng et al., 2014). The ability of cancer cells to disseminate to distant regions is partly the result of microtubule dy*
Project supported by the Taylor’s Research Grant Scheme (No. TRGS/MFS/2/2013/SBS/003) # Electronic supplementary materials: The online version of this article (https://doi.org/10.1631/jzus.B2000278) contains supplementary materials, which are available to authorized users ORCID: Mee Lee LOOI, https://orcid.org/0000-0001-5415-6973 © Zhejiang University and Springer-Verlag GmbH Germany, part of Springer Nature 2020
namics. Microtubules are part of the cell cytoskeleton, contribute to shape and dynamics, and are essential for cell movement and directionality (Ganguly et al., 2012; Mukhtar et al., 2014). As a result of rapid cancer cell division, anti-mitotic drugs that potentially target microtubule dynamics have been suggested to be the best cancer therapeutic agents (Mukhtar et al., 2014). The potential of PB in targeting cancer cell migration was investigated in this study. The modulation effect of PB on microtubule structure and networks was also observed in comparison to a standard microtubule inhibitor, paclitaxel. The sub-toxic levels of PB and 5-FU were used to ensure no cell cytotoxicity in the cell migration analysis. After 24 h of respective treatment, values of IC20 (20% inhibitory concentration) and IC30 (30% inhibitory concentration) recorded for PB on human lung adenocarcinoma (A549) cells were 20 and 100 μg/mL, respectively,
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