A Study on Cytotoxic and Apoptotic Potential of a Triterpenoid Saponin (3-O-α-L-Arabinosyl Oleanolic Acid) Isolated fromSchumacheria castaneifoliaVahl in Human Non-Small-Cell Lung Cancer (NCI-H292) Cells

Abstract

Lung cancer is the major cause of cancer death among men. A number of natural compounds have proven to be useful in the treatmet of lung cancer. This study was aimed to determine cytotoxic and apoptotoic effects of a natural compound 3-O-α-L-arabinosyl oleanolic acid (3-O-L-AO) isolated from Schumacheria castaneifolia in non-small-cell lung cancer (NCI-H292) cells. Cytotoxic effects of 3-O-L-AO were determined by Sulforhodamine B (SRB) assay and apoptotic effects were tested by evaluating (a) apoptotsis related morphological changes, (b) caspase 3/7 activity, and (c) expression of Bax, p53, and survivin genes. Oxidative stress markers (reactive oxygen species (ROS), glutathione-S-transferase (GST), and glutathione (GSH)) were also analysed in 3-O-L-AO treated NCI-H292 cells. 3-O-L-AO exerted potent cytotoxic effects in NCI-H292 cells while being less cytotoxic to normal lung (MRC-5) cells. Exposure to 3-O-L-AO caused upregulation of Bax and p53 and downregulation of survivin in NCI-H292 cells. Activation of caspase 3/7 and morphological features related to apoptosis further confirmed 3-O-L-AO induced apoptosis. Furthermore, elevated ROS and GST levels and decreased GSH levels suggested 3-O-L-AO can induce apoptosis, possibly causing oxidative stress in NCI-H292 cells. Overall results suggest that 3-O-L-AO can be considered as an effective anticancer agent for the treatment of lung cancer.

Prodigiosin-Emerged PI3K/Beclin-1-Independent Pathway Elicits Autophagic Cell Death in Doxorubicin-Sensitive and -Resistant Lung Cancer

“…Another study showed crude extract of Neosartorya laciniosa KUFC 7896 and Neosartorya tsunodae KUFC 9213 potentiated doxorubicin tumoricidal activity by increasing Dox accumulation in lung cancer nuclei [ 37 ]. Of note, natural compounds such as curcumin and β-asarone from the Chinese herb Acorus tatarinowii [ 38 , 39 ] have showed their tumoricidal activity by reducing the Wnt/β-catenin signaling pathway, by enhancing current chemotherapeutic drugs, for example, curcumin and phloretin [ 40 , 41 ], and by inducing intrinsic or extrinsic apoptotic pathways, including waltonitone, matrine, oxymatrine, astragalin (kaempferol-3- O -β-d-glucoside), and 3- O -α-l-arabinosyl oleanolic acid from Schumacheria castaneifolia Vahl [ 42 , 43 , 44 , 45 , 46 ]. Some natural compounds’ inhibited growth factor have overcome drug resistance, for example, granulatimide, danorubicin, penicinoline, austocystin D, equol, kaempferol, resveratrol, ellagic acid, and butein [ 47 , 48 , 49 ].…”

Novel Synthesized N-Ethyl-Piperazinyl-Amides of C2-Substituted Oleanonic and Ursonic Acids Exhibit Cytotoxic Effects through Apoptotic Cell Death Regulation

“…The intervention of pentacyclic triterpenes on genes involved in the intrinsic mitochondrial apoptotic pathway has been previously reported; the diamine-(PEG)ylated oleanolic acid clearly up-regulated caspase-8, caspase-9, caspase-3, and Bak, and down-regulated Bcl-2 [71]. Conversely, 3-O-α-L-arabinosyl oleanolic acid caused up-regulation of Bax [72]. Similarly, ursolic acid reduced the expression of Bcl-2 and increased the level of the apoptotic protein Bax [73].…”

Methylenetetrahydrofolate Dehydrogenase 1 Silencing Expedites the Apoptosis of Non-Small Cell Lung Cancer Cells via Modulating DNA Methylation

“…Subsequently, the apoptosis mechanism of si-MTHFD1 in NCI-H1299 cells was investigated by detecting the apoptosis-related factors, including p53, survivin, Bax, and Bcl-2. Samarakoon et al showed that triterpenoid saponin significantly facilitated the apoptosis of NSCLC cells via enhancing p53 and Bax expression and decreasing survivin levels [ 34 ]. Another study revealed that miR-145 upregulation promoted the apoptosis of NSCLC cells through augmenting the Bax/Bcl-2 ratio [ 35 ].…”