A triterpenediol from Boswellia serrata induces apoptosis through both the intrinsic and extrinsic apoptotic pathways in human leukemia HL-60 cells

Abstract

A triterpenediol (TPD) comprising of isomeric mixture of 3alpha, 24-dihydroxyurs-12-ene and 3alpha, 24-dihydroxyolean-12-ene from Boswellia serrata induces apoptosis in cancer cells. An attempt was made in this study to investigate the mechanism of cell death by TPD in human leukemia HL-60 cells. It inhibited cell proliferation with IC50 approximately 12 microg/ml and produced apoptosis as measured by various biological end points e.g. increased sub-G0 DNA fraction, DNA ladder formation, enhanced AnnexinV-FITC binding of the cells. Further, initial events involved massive reactive oxygen species (ROS) and nitric oxide (NO) formation, which were significantly inhibited by their respective inhibitors. Persistent high levels of NO and ROS caused Bcl-2 cleavage and translocation of Bax to mitochondria, which lead to loss of mitochondrial membrane potential (Deltapsim) and release of cytochrome c, AIF, Smac/DIABLO to the cytosol. These events were associated with decreased expression of survivin and ICAD with attendant activation of caspases leading to PARP cleavage. Furthermore, TPD up regulated the expression of cell death receptors DR4 and TNF-R1 level, leading to caspase-8 activation. These studies thus demonstrate that TPD produces oxidative stress in cancer cells that triggers self-demise by ROS and NO regulated activation of both the intrinsic and extrinsic signaling cascades.

Evidence Based Phytopharmacological Potential of Herbal Extracts in Post-Ingestion Management of Mycotoxins in Animal Models

“…Galangal rhizomes (Alpinia officinarum) from the botanical family of Zingiberaceae have chemoprevention effect on tumor [95]. The same has been reported for ginger (Zingiber officinale) [96], Frankincense resins (Gum olibanum) [97], Myrrh (Commiphora myrrha) [98], Cinnamon barks (Cimmomum zeylanicum) [99]. Herbal extracts from these plants demonstrate possible significant hepatoprotection potential in cancer induced by aflatoxin B1 [100].…”

2,4,3′,4′-tetramethoxy-biphenyl induces apoptosis in MGC-803 cells through a mitochondrial/caspase pathway

“…Consequently, cytochrome C expression was more in cytosol which might be due to its release from mitochondria as an apoptotic event. Moreover, the loss of mitochondrial membrane potential (ΔΨm) is facilitated through opening of mitochondrial permeability transition pores (PTP) largely due to Bax translocation, which in turn, conduct the leakage of cytochrome C and pro-apoptotic proteins from mitochondria to the cytosol (Bhushan et al, 2007). Translocation of these proteins impairs mitochondrial functions and brings the cells to a "point of no return" to enter apoptosis via activation of caspases.…”

Antimycin A-induced cell death depends on AIF translocation through NO production and PARP activation and is not involved in ROS generation, cytochrome c release and caspase-3 activation in HL-60 cells

“…In HL-60 cells, the activation of inducible NOS was reported. 12 Therefore, it may be considered that AA-induced cell death is involved in NO production by inducible NOS.…”

“…9,10 In addition, NO-induced apoptosis of HL-60 cells has also been reported. 11,12 PARP is an abundant nuclear enzyme that is activated by DNA strand breaks or kinks. [13][14][15] Activated PARP consumes nicotinamide adenine dinucleotide (NAD + ) to transfer poly(ADP-ribose) to specific acceptor proteins.…”