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Chem Biol Interact. 2017 Aug 1;273:37-47. doi: 10.1016/j.cbi.2017.05.022. Epub 2017 Jun 2.

Intrinsic capabilities of Leptospermum javanicum in inducing apoptosis and suppressing the metastatic potential of human lung carcinoma cells.

Author information

1
Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
2
Biology Division, Centre for Foundation Studies in Science, University of Malaya, Kuala Lumpur, Malaysia.
3
Rimba Ilmu Botanic Garden, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
4
School of Science, Monash University Malaysia, 47500 Selangor, Malaysia.
5
Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: simkaeshin@um.edu.my.

Abstract

The active isolate of LF1 in Leptospermum javanicum was further looked into its capabilities in provoking an apoptotic reaction and suppressing the metastasis process in treated non-small lung cancer cells. LF1 underwent isolation and purification to yield a white powder which was identified as Betulinic acid (BA) via NMR, LCMS and IR spectroscopy. The isolate, BA, which produced an encouraging cytotoxic effect against non-small lung cancer cells (A549 and NCI-H1299) through the MTT assay, was further assessed with TUNEL, Sub-G1 population quantification, acridine orange/ethidium bromide staining as well as activated caspase-3 detection. The results pointed towards the induction of apoptosis as a result of increasing doses of BA, regardless of the p53 status in both cell lines. Treatment with BA also prevented an effective attachment of the invasive A549 cells onto a new culture surface in addition to diminishing the migratory potential of treated cells across a porous membrane. Further investigation through the ELISA detection and gelatin zymography showed an adverse effect to production of matrix metalloproteinase-2 (MMP-2) while the levels of matrix metalloproteinase-9 (MMP-9) were not negatively affected. The findings from this study validate the potential of L. javanicum as a potential anti-cancer treatment as stated in our previous study. The isolate, BA not only showed a capacity in inducing apoptotic cell death in non-small lung cancer cells, but managed to distort the ability of the cancer cells in effectively undergoing the metastasis process.

KEYWORDS:

Anti-metastatic; Apoptosis; Betulinic acid; Cell cycle arrest; Leptospermum javanicum; Matrix metalloproteinase

PMID:
28578903
DOI:
10.1016/j.cbi.2017.05.022
[Indexed for MEDLINE]

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