Data on cytotoxic pattern of cholesterol analogs for lung adenocarcinoma cells.
Delgado Yamixa,Torres Anamaris,Milian Melissa
Data in brief
Cholesterol (Cho) is a sterol that plays an essential role in the maintenance of biologic cell membranes, and various lipoproteins are its carriers through blood circulation [1]. Some FDA-approved anticancer drugs (i.e., Lipoplatin and Myocet) are conjugated to Cho moieties to improve their pharmacokinetic properties, cellular uptake and target specificity [2]. Recently natural and synthetic sterol compounds have shown a broad spectrum of pharmacological activities [3,4]. Herein, we investigated the anticancer activity of various natural Cho analogs, ie. asiatic acid (AsA), betulinic acid (BeA), oleanolic acid (OleA), ursolic Acid (UrA), lupeol (Lupe) and β-sitosterol (β-Sito) against non-small cell lung adenocarcinoma (A549). We performed theoretical calculations of the biophysicochemical properties, and viability assays in a range of 5-100 μM in A549 cells of these Cho analogs. We used ChemSketch and ChemSpider to determine physical properties, and GraphPad Prism 8 software for the data analysis to determine the inhibitory concentrations at 50% (IC) of each compound.
10.1016/j.dib.2019.104179
Olean-28,13b-olide 2 plays a role in cisplatin-mediated apoptosis and reverses cisplatin resistance in human lung cancer through multiple signaling pathways.
Zhu Bin,Ren Caiping,Du Ke,Zhu Hecheng,Ai Yong,Kang Fenghua,Luo Yi,Liu Weidong,Wang Lei,Xu Yang,Jiang Xingjun,Zhang Yihua
Biochemical pharmacology
Lung cancer, similar to other chronic diseases, occurs due to perturbations in multiple signaling pathways. Mono-targeted therapies are not ideal since they are not likely to be effective for the treatment and prevention of lung cancer, and are often associated with drug resistance. Therefore, the development of multi-targeted agents is required for novel lung cancer therapies. Thioredoxin reductase (TrxR or TXNRD1) is a pivotal component of the thioredoxin (Trx) system. Various types of tumor cells are able to overexpress TrxR/Trx proteins in order to maintain tumor survival, and this overexpression has been shown to be associated with clinical outcomes, including irradiation and drug resistance. Emerging evidence has indicated that oleanolic acid (OA) and its derivatives exhibit potent anticancer activity, and are able to overcome drug resistance in cancer cell lines. In the present study, it was demonstrated that a novel synthesized OA family compound, olean-28,13b-olide 2 (OLO-2), synergistically enhanced cisplatin (CDDP)-mediated apoptosis, led to the activation of caspase-3 and the generation of reactive oxygen species (ROS), induced DNA damage, and inhibited the activation of the extracellular-signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), AKT and nuclear factor-κB (NF-κB) pathways in human multidrug-resistant A549/CDDP lung adenocarcinoma cells. Subsequent analyses revealed that OLO-2 inhibited P-glycoprotein (P-gp or ABCB1) and TrxR by reducing their expression at the protein and mRNA levels, and by suppressing P-gp ATPase and TrxR activities. Further biological evaluation indicated that OLO-2 significantly reduced Trx and excision repair cross-complementary1 (ERCC1) protein expression and significantly inhibited the proliferation of drug-sensitive (A549) and multidrug-resistant (A549/CDDP) non-small cell lung cancer (NSCLC) cells, but had no effect on non-tumor lung epithelial-like cells. In addition, the present study demonstrated, for the first time, to the best of our knowledge, that overexpressing or knocking down TrxR in NSCLC cells enhanced or attenuated, respectively, the resistance of NSCLC cells against CDDP, which indicated that TrxR plays an important role in CDDP resistance and functions as a protector of NSCLC against chemotherapeutic drugs. OLO-2 treatment also exhibited up to 4.6-fold selectivity against human lung adenocarcinoma cells. Taken together, the results of the present study shed light on the drug resistance-reversing effects of OLO-2 in lung cancer cells.
10.1016/j.bcp.2019.113642
Anticancer effect of SZC015 on lung cancer cells through ROS-dependent apoptosis and autophagy induction mechanisms in vitro.
Sun Bin,Gao Lei,Ahsan Anil,Chu Peng,Song Yanlin,Li Hailong,Zhang Zonghui,Lin Yuan,Peng Jinyong,Song Zhicheng,Wang Shisheng,Tang Zeyao
International immunopharmacology
Oleanolic acid (OA) and its several derivatives possess various pharmacological activities, such as antitumor and anti-inflammation. In present study, anticancer effect of SZC015, an OA derivative, and its underlying mechanisms were investigated. We demonstrated that cell viability was significantly decreased in SZC015-treated lung cancer cells, but has less cytotoxicity in human bronchial epithelial cell line. Further investigation verified that apoptosis and autophagy induction and G/G phase arrest were observed in SZC015-treated H322 cells. Mechanically, the level of Akt, p-Akt, p-IκBα, and total p65, the p-p65 in the cytoplasm and nucleus were suppressed by SZC015 in H322 cells, respectively. Inhibition of p65 nuclear translocation was also confirmed by immunofluorescence staining. In addition, co-treatment with chloroquine, an autophagy inhibitor, significantly inhibited SZC015-induced autophagy and enhanced SZC015-induced apoptotic cell death. Intracellular ROS was increased in a concentration-dependent manner, which could be prevented by N-Acetyl l-Cysteine, an ROS scavenger. Moreover, the level of Akt and procaspase-3 were increased, while the ratio of LC3 II/I was decreased. Taken together, our study demonstrates that the inhibitory effect of SZC015 against H322 cells is mediated by excessive ROS generation that could suppress Akt/NF-κB signaling pathway, which thereby leads to apoptotic and autophagic cell death.
10.1016/j.intimp.2016.09.026
Ursolic and Oleanolic Acids Induce Mitophagy in A549 Human Lung Cancer Cells.
Molecules (Basel, Switzerland)
Ursolic and oleanolic acids are natural isomeric triterpenes known for their anticancer activity. Here, we investigated the effect of triterpenes on the viability of A549 human lung cancer cells and the role of autophagy in their activity. The induction of autophagy, the mitochondrial changes and signaling pathway stimulated by triterpenes were systematically explored by confocal microscopy and western blotting. Ursolic and oleanolic acids induce autophagy in A549 cells. Ursolic acid activates AKT/mTOR pathways and oleanolic acid triggers a pathway independent on AKT. Both acids promote many mitochondrial changes, suggesting that mitochondria are targets of autophagy in a process known as mitophagy. The PINK1/Parkin axis is a pathway usually associated with mitophagy, however, the mitophagy induced by ursolic or oleanolic acid is just dependent on PINK1. Moreover, both acids induce an ROS production. The blockage of autophagy with wortmannin is responsible for a decrease of mitochondrial membrane potential (Δψ) and cell death. The wortmannin treatment causes an over-increase of p62 and Nrf2 proteins promote a detoxifying effect to rescue cells from the death conducted by ROS. In conclusion, the mitophagy and p62 protein play an important function as a survival mechanism in A549 cells and could be target to therapeutic control.
10.3390/molecules24193444
A Study on Cytotoxic and Apoptotic Potential of a Triterpenoid Saponin (3-O--L-Arabinosyl Oleanolic Acid) Isolated from Vahl in Human Non-Small-Cell Lung Cancer (NCI-H292) Cells.
Samarakoon Sameera R,Ediriweera Meran K,Nwokwu Chukwumaobim Daniel Uzochukwuwulu,Bandara Chamara Janaka,Tennekoon Kamani H,Piyathilaka Poorna,Karunaratne D Nedra,Karunaratne Veranja
BioMed research international
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--L-arabinosyl oleanolic acid (3-O-L-AO) isolated from 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 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 and and downregulation of 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.
10.1155/2017/9854083
The dual induction of apoptosis and autophagy by SZC014, a synthetic oleanolic acid derivative, in gastric cancer cells via NF-κB pathway.
Rui Li Xiao,Shu Song Yu,Jun Wu Jing,Mo Chen Zi,Wu Sun Zheng,Min Liu Shu,Yuan Lin,Yong Peng Jin,Cheng Song Zhi,Sheng Wang Shi,Yao Tang Ze
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
Oleanolic acid (OA) possesses various pharmacological activities, such as antitumor and anti-inflammation; however, its clinical applications are limited by its relatively weak activities and low bioavailability. In this study, we evaluated the cytotoxic activity of seven novel OA derivatives, one of which, SZC014 [2-(pyrrolidine-1-yl) methyl-3-oxo-olean-12-en-28-oic acid], exhibited the strongest antitumor activity; its anticancer effect on gastric cancer cells and action mechanisms were investigated. The viability of OA and seven synthesized derivatives treating gastric cancer cells was detected using tetrazolium (MTT). Among them, SZC014 exhibited the strongest cytotoxic activity against gastric cancer cells (SGC7901, MGC803, and MKN-45). The effect of SZC014 on cell cycle was identified by propidium iodide (PI) staining assay. The cellular apoptosis induced by SZC014 was tested by annexin V/PI. The cellular morphological changes and ultrastructural structures affected by SZC014 were observed and imaged through inverted phase contrast microscope and transmission electron microscopy. Western blotting was performed to explore the expression of proteins associated with apoptosis (caspase 3, caspase 9, Bax, Bcl-2, and Bcl-xL), autophagy (Beclin 1 and ATG 5), and nuclear factor-κB (NF-κB) signal pathway, respectively. The cytotoxic activities of all the seven synthesized OA derivatives were stronger than that of OA against gastric cancer cells. SZC014 exhibited stronger cytotoxic activity than other OA derivatives, inhibited the proliferation of gastric cancer cells, besides, induced G2/M phase cell cycle arrest in SGC7901 cells. Both apoptosis and autophagy were found simultaneously in SZC014-treated SGC7901 cells. Caspase-dependent apoptosis induced by SZC014 was confirmed to be associated with upregulation of Bax and downregulation of Bcl-2 and Bcl-xL, while upregulation of Beclin 1 and ATG 5 was inferred to be involved in SZC014-induced autophagy. Moreover, treating cells with SZC014 resulted in a decrease in phosphorylation of IκBα and NF-κB/p65 and NF-κB/p65 nuclear translocation. The cytotoxic activities of seven OA derivatives were generally stronger than that of OA, among which, SZC014 possessed the most potent anticancer activity in SGC7901 cells and would be a promising chemotherapic agent for the treatment of gastric cancer.
10.1007/s13277-015-4293-2
Anticancer effect of SZC017, a novel derivative of oleanolic acid, on human gastric cancer cells.
Gao Lei,Xu Zhen,Wang Yan,Sun Bin,Song Zhicheng,Yang Bining,Liu Xu,Lin Yuan,Peng Jinyong,Han Guozhu,Wang Shisheng,Tang Zeyao
Oncology reports
Oleanolic acid (OA) and its several derivatives possess chemopreventive and chemotherapeutic functions against a series of cancer types. Many chemotherapeutic compounds are effective in improving the quality of life and prolonging the survival of patients with gastric cancer, therefore progress in the treatment of gastric cancer, especially the anticancer effects of OA derivatives must be achieved. The inhibitory effect of SZC017, a newly synthesized derivative of OA, on cell viability was determined by MTT assay. Furthermore, flow cytometry, transmission electron microscopy, and western blot analysis revealed that the inhibition of cell viability by OA was mediated by triggering the intrinsic apoptosis of gastric cancer cells, and inducing S phase arrest of SGC7901 cells. Mechanistically, SZC017 was effective against gastric cancer cells via inhibiting Akt/NF‑κB signaling and topoisomerase I and IIα proteins. Taken together, our data indicate that SZC017 may be a potential chemotherapeutic agent against gastric cancer cells.
10.3892/or.2015.4447