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

• Published in: Journal of applied biomedicine Vol. 15; no. 1; pp. 71 - 80
• Main Authors: Asif, Muhammad, Al-Mansoub, Majed Ahmed, Khan, MD Shamsuddin Sultan, Yehya, Ashwaq Hamid Salem, Ezzat, Mohammed Oday, Oon, Chern Ein, Atif, Muhammad, Abdul Majid, Aman Shah, Abdul Majid, Amin Malik Shah
• Format: Journal Article
• Language: English
• Published: Elsevier Sp. z o.o 01.01.2017
• Subjects: Mesua ferrea; Programmed cell death; ROS; Signalling pathways; Terpenes; Signalling pathways; Programmed cell death; Terpenes; Mesua ferrea; ROS
• ISSN: 1214-021X; 1214-0287
• DOI: 10.1016/j.jab.2016.10.003

Proposed molecular mechanisms responsible for selective cytotoxic activity of Mesua ferrea stem bark extract towards human colorectal carcinoma cells. [Display omitted] •Mesua ferrea stem bark extract showed potent cytotoxicity towards HCT 116 cells.•GC–MS analysis revealed that it was majorly comprised of terpenes.•F-3 modulated the expression of NF-κB and HIF-1α cell signalling pathways.•F-3 down-regulated the activity of Bcl-2, survivin, xIAP and HSP60 proteins.•F-3 up-regulated the activity of TRAILR-1, TRAILR-2 and caspases-3 in HCT 116 cells. 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.