Intrinsic capabilities of Leptospermum javanicum in inducing apoptosis and suppressing the metastatic potential of human lung carcinoma cells. (1st August 2017)

• Record Type: Journal Article
• Authors: Navanesan, Suerialoasan; Abdul Wahab, Norhanom; Manickam, Sugumaran; Cheow, Yuen Lin; Sim, Kae Shin
• Is Part Of: Chemico-biological interactions. Volume 273(2017)
• Page Start: 37
• Page End: 47
• Publication Date: 2017-08-01
• Subjects: Leptospermum javanicum -- Betulinic acid -- Apoptosis -- Cell cycle arrest -- Anti-metastatic -- Matrix metalloproteinase; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.05.022
• Languages: English
• ISSNs: 0009-2797

Abstract

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. Highlights: Betulinic Acid (BA) was isolated form Leptospermum javanicum (syn. L. flavescens) . Isolated compound caused apoptosis in treated lung cancer cells. Prevention of adhesion and migration occurred in treated cells. Cell cycle arrest in treated cells restricts the growth and development. BA decreases expression of MMP-2 but not MMP-9 in TGF-β1 stimulated cells.