J Appl Biomed 15:71-80, 2017 | DOI: 10.1016/j.jab.2016.10.003

Molecular mechanisms responsible for programmed cell death-inducing attributes of terpenes from Mesua ferrea stem bark towards human colorectal carcinoma HCT 116 cells

Muhammad Asifa,*, Majed Ahmed Al-Mansoubb, MD Shamsuddin Sultan Khana, Ashwaq Hamid Salem Yehyac, Mohammed Oday Ezzatd, Chern Ein Oonc, Muhammad Atife, Aman Shah Abdul Majidf, Amin Malik Shah Abdul Majida,g,*
a EMAN Testing and Research laboratory, Department of Pharmacology, School of Pharmaceutical Sciences, Universti Sains Malaysia, Penang 11800, Malaysia
b Department of Pharmacology, School of Pharmaceutical Sciences, Universti Sains Malaysia, Penang 11800, Malaysia
c Institute for Research in Molecular Medicine (INFORMM), Universti Sains Malaysia, Penang, 11800, Malaysia
d Centre for Drug Research, Universti Sains Malaysia, Penang, 11800, Malaysia
e Department of Pharmacy, The Islamia University of Bahawalpur, 63100, Punjab, Pakistan
f Advanced Medical and Dental Institute, Universti Sains Malaysia, Penang 13200, Malaysia
g ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, Australian National University, Australia

The current study explored the in vitro anticancer properties of Mesua ferrea stem bark (SB) extract towards human colon carcinoma HCT116 cells. SB was successively extracted with different solvents using soxhlet apparatus. MTT assay was employed to test toxicity against different cancer and normal cell lines. Active extract (n-Hexane) was fractionated by column chromatography (CC) to get the most active fraction (F-3). Series of in vitro assays were employed to characterize cytotoxic nature of F-3. Antioxidant properties of F-3 were assessed using DPPH, ABTS and FRAP assays followed by GC-MS analysis. Intracellular ROS levels were measured by DCFH-DA fluorescent assay. Finally, cell signalling pathways and their downstream proteins targeted by F-3 were studied using 10-cancer pathway and human apoptosis protein profilers and in silico docking studies. n-Hexane extract and its fraction (F-3) showed potent anti-proliferative effect against HCT 116. Programmed cell death (PCD) studies showed that F-3 modulated the expression of multiple proteins in HCT 116. F-3 showed weak antioxidant activity in all the models, while significant increase in ROS was observed in HCT 116. GC-MS analysis revealed that F-3 was majorly comprised of terpenes. Data of pathway profiler and in silico studies revealed that F-3 down-regulated the expression of NF-κB and HIF-1α pathways. Overall these results demonstrate that anticancer effects of M. ferrea stem bark towards human colon carcinoma are mainly due to its terpenes contents.

Keywords: Mesua ferrea; Terpenes; Programmed cell death; ROS; Signalling pathways

Received: November 1, 2015; Revised: September 30, 2016; Accepted: October 6, 2016; Published: January 1, 2017  Show citation

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Asif M, Al-Mansoub MA, Sultan Khan S, Yehya AHS, Oday Ezzat M, Ein Oon C, et al.. Molecular mechanisms responsible for programmed cell death-inducing attributes of terpenes from Mesua ferrea stem bark towards human colorectal carcinoma HCT 116 cells. J Appl Biomed. 2017;15(1):71-80. doi: 10.1016/j.jab.2016.10.003.
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