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

Abstract

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 downregulated the expression of NF-kB and HIF-1a pathways. Overall these results demonstrate that anticancer effects of M. ferrea stem bark towards human colon carcinoma are mainly due to its terpenes contents.

Ethnobotanical and Phytopharmacological attributes of Mesua ferrea: A mini review

“…Interestingly, oleo-gum resin extract did not induce toxicity in the normal colon cells (CCD-18co) (Asif et al, 2016) Similarly, Asif et al in their recent study showed that terpenes rich stem bark extract has broad spectrum anticancer activities. The order of sensitivity (high to low) of cancer cell lines towards F-3 was HCT 116 > MNK-74 > PC-3 > T-47D > MIA PaCa-2 > HT-29 > PANC-1 > MCF-7 > Capan-1 > EA.hy926 > 3T3-L1 > CCD-18co respectively (Asif et al, 2017). In addition to variety of in vitro anticancer studies, there is also one study that reports the in vivo efficacy of chloroform and ethyl acetate extract of M. ferrea flowers against Ehrlich ascites carcinoma in Swiss albino mice.…”

Complete chloroplast genome of Mesua ferrea: the first Calophyllaceae plastome

“…Recently, researchers confirmed that the anticancer bioactive compound of M. ferrea was terpene (Asif et al. 2017 ). The extract of M. ferrea also showed antiarthritic, antioxidant, and antibacterial activity (Jalalpure et al.…”

“…The extracts of M. ferrea showed anticancer bioactive on human pancreatic cancer cell line (Rajendran et al 2016). Recently, researchers confirmed that the anticancer bioactive compound of M. ferrea was terpene (Asif et al 2017). The extract of M. ferrea also showed antiarthritic, antioxidant, and antibacterial activity (Jalalpure et al 2011;Chahar et al 2013).…”