Abstract:
:The cytotoxic potential of a naturally occurring indoloquinazoline alkaloid, soyauxinium chloride (SCHL), was determined on a broad panel of animal and human cancer cell lines, including various sensitive and drug-resistant phenotypes. The cytotoxicity, SCHL-induced autophagic, ferroptotic, and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). Caspase-Glo assay was used to detect the activity of caspases using spectrophotometric analysis. Flow cytometry was applied for cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). SCHL and doxorubicin (reference molecule) exhibited cytotoxic effects towards the 18 cancer cell lines tested. The IC50 values obtained ranged from 3.64 μM (towards CCRF-CEM leukemia cells) to 16.86 μM (against the BRAF-wildtype SKMel-505 melanoma cells for SCHL). Collateral sensitivity of the resistant HCT116 p53-/- colon adenocarcinoma cells to SCHL was observed as well as the normal sensitivity of CEM/ADR5000 leukemia cells, MDA-MB-231-BCRP breast adenocarcinoma cells and U87. MGΔEGFR glioblastoma cells. SCHL induced apoptosis in CCRF-CEM cells via caspases 3/7-, 8- and 9-activation, MMP alteration and increased ROS production, and otherwise ferroptosis and necroptosis. SCHL is a prominent cytotoxic alkaloid that should be further studied to develop a novel drug to combat cancers including refractory phenotypes.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Mbaveng AT,Noulala CGT,Samba ARM,Tankeo SB,Abdelfatah S,Fotso GW,Happi EN,Ngadjui BT,Beng VP,Kuete V,Efferth Tdoi
10.1016/j.cbi.2020.109334subject
Has Abstractpub_date
2021-01-05 00:00:00pages
109334eissn
0009-2797issn
1872-7786pii
S0009-2797(20)31410-1journal_volume
333pub_type
杂志文章abstract::Novel therapeutics to overcome the toxic effects of organophosphorus (OP) chemical agents are needed due to the documented use of OPs in warfare (e.g. 1980-1988 Iran/Iraq war) and terrorism (e.g. 1995 Tokyo subway attacks). Standard OP exposure therapy in the United States consists of atropine sulfate (to block muscar...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2010.02.015
更新日期:2010-09-06 00:00:00
abstract::Naphthalene is considered by the US Environmental Protection Agency to be a carcinogenic compound based on inhalation studies in rats. The primary metabolite of naphthalene is naphthalene 1,2-arene oxide. This unstable intermediate can lead to formation of 1-naphthol and naphthalene-1,2-dihydrodiol. Secondary metaboli...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2006.12.007
更新日期:2007-02-20 00:00:00
abstract::Acetaldehyde (AA) and methylglyoxal (MG) are reactive, ubiquitous aldehydes, present in the environment and endogenously formed in animals and humans. They have both been shown to readily form DNA adducts under simulated physiological conditions. We report here on the use of cultured normal and SV40T antigen-immortali...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(97)00107-5
更新日期:1998-01-30 00:00:00
abstract::Aldehyde dehydrogenase 2 (ALDH2) catalyzes oxidation of toxic aldehydes to carboxylic acids. Physiologic levels of Mg(2+) ions influence ALDH2 activity in part by increasing NADH binding affinity. Traditional fluorescence measurements monitor the blue shift of the NADH fluorescence spectrum to study ALDH2-NADH interac...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2011.01.023
更新日期:2011-05-30 00:00:00
abstract::Within the alpha/beta hydrolase fold superfamily of proteins, the COesterase group (carboxylesterase type B, block C, cholinesterases …) diverged from the other groups through simultaneous integration of an N-terminal, first disulfide bond and a significant increase in the protein mean size. This first disulfide bond ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2019.05.016
更新日期:2019-08-01 00:00:00
abstract::The relative toxicities of particulate beryllium phosphate, soluble beryllium sulphate and a beryllium sulphosalicylate complex to a rat liver parencymal derived cell line have been examined in culture. Due to the propensity of beryllium salts to form beryllium phosphate in solution the incubation medium used was free...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(79)90100-5
更新日期:1979-01-01 00:00:00
abstract::Melatonin and S-adenosyl-l-methionine (SAMe) prevent oxidative stress and tissue dysfunction in obstructive jaundice (OJ). Lipid peroxidation is exacerbated in the presence of trace amounts of iron (Fe). The study investigated the regulation by melatonin and SAMe the induction of oxidative stress, iron metabolism dist...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2008.05.016
更新日期:2008-07-30 00:00:00
abstract::The objectives of the present work were to study the effects of certain peroxisome proliferators on xenobiotic-metabolizing enzyme activities in the testes of normal and hypothyroid rats, i.e. phenol sulfotransferases (pST), phenol UDP-glucuronosyl transferases (pUDPGT), glutathione transferases (GST), catalase, epoxi...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(97)00020-3
更新日期:1997-05-02 00:00:00
abstract::The ochratoxin A (OTA) metabolite (4R)-4-hydroxyochratoxin A [4R)-OTA) inhibits the aminoacylation of phenylalanine tRNA catalyzed by phenylalanyl-tRNA synthetase (PheRS) with a Ki-value of 0.9 mM as compared to 1.3 mM for OTA. It also inhibits protein synthesis and cell growth in the same manner as OTA. Ochratoxin al...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(83)90160-6
更新日期:1983-11-01 00:00:00
abstract::The effect of repeated parenteral administration of cadmium (0.75, 1.5 and 3.0 mg/kg) on tissue disposition and urinary excretion of cadmium, zinc, copper and iron has been studied in the male rat. Cadmium, zinc and copper accumulated in liver and kidney, but the concentration of iron did not alter significantly. The ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(79)90137-6
更新日期:1979-10-01 00:00:00
abstract::The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human periph...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2015.03.019
更新日期:2015-05-25 00:00:00
abstract::Sophoricoside (SOPH) is an isoflavone glycoside isolated from the fruits of Sophora japonica. Since its first isolation in 1961, there are rare findings about the effects of SOPH on reproductive system. In the present study, the pregnant mice administrated by different doses of SOPH were used to explore the effect of ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2014.05.009
更新日期:2014-08-05 00:00:00
abstract::The metabolism of [3H]benzo[a]pyrene (BP) and (-)-trans-[14C]7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) was studied in freshly isolated hepatocytes of the wild benthic fish, brown bullhead (Ictalurus nebulosus). Bullhead hepatocytes incubated with 40 microM [3H]BP for 1 h metabolized BP to water soluble met...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(90)90063-s
更新日期:1990-01-01 00:00:00
abstract::Oxalate induced renal calculi formation and the associated renal injury is thought to be caused by free radical mediated mechanisms. An in vivo model was used to investigate the effect of phycocyanin (from Spirulina platensis), a known antioxidant, against calcium oxalate urolithiasis. Male Wistar rats were divided in...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2004.05.006
更新日期:2004-08-10 00:00:00
abstract::Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM) that worsens its morbidity and mortality. There is evidence that camel milk (CM) improves the glycemic control in DM but its effect on the renal complications especially the DN remains unclear. Thus the current study aimed to ch...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2015.01.013
更新日期:2015-03-05 00:00:00
abstract::Glycidyl ethers are used in epoxy resins. Epoxy resins are widely used in adhesives and coatings, as well as in electronics and structural composites, thus there is a potential of human exposure to glycidyl ethers. The aim of the present investigation was to explore the utility of haemoglobin adducts for biomonitoring...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(96)03744-1
更新日期:1997-01-24 00:00:00
abstract::Styrene oxide was reacted with deoxynucleosides and DNA in aqueous buffer at pH 7.4. The products were purified by HPLC, characterized by UV spectroscopy and by chemical ionization mass spectrometry. The main products identified were 7-alkyl-, N2-alkyl- and O6-alkyldeoxyguanosine, 1-alkyl-, and N6-alkyldeoxyadenosine,...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(86)90055-4
更新日期:1986-12-01 00:00:00
abstract::11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) physiologically catalyzes the interconversion of receptor-active 11-hydroxy glucocorticoids (cortisol) to their receptor-inactive 11-oxo metabolites (cortisone), thereby acting as important pre-receptor control device in regulating access of glucocorticoid horm...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(02)00180-1
更新日期:2003-02-01 00:00:00
abstract::Isolated rat hepatocytes were used to investigate the biochemical mechanisms of toxicity of triethyllead (Et3Pb+), a highly neurotoxic degradation product of the antiknocking petrol additive tetraethyllead. As early as 5 min from the addition of 50 microM Et3Pb+ to hepatocyte suspensions a decrease of mitochondrial me...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(94)90111-2
更新日期:1994-01-01 00:00:00
abstract::Genotoxic and clastogenic effects of styrene were studied in mice. Male NMRI mice were exposed by inhalation to styrene in concentrations of 750 and 1500 mg/m3 for 21, 7, 3 and 1 days (6 h/day, 7 days/week). Followed parameters included styrene in blood, specific styrene oxide (SO) induced DNA adducts, DNA strand brea...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(01)00253-8
更新日期:2001-09-28 00:00:00
abstract::Colon epithelium is made up of two general classes of cells, surface cells which are post-mitotic and crypt cells which contain the proliferative population. Their relative vulnerability to environmental damage and ability to perform DNA repair are important issues in colon carcinogenesis. DNA damage and repair was st...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(85)90026-2
更新日期:1985-01-01 00:00:00
abstract::Fatty liver is the earliest and most common response of the liver to consumption of excessive alcohol. Steatosis can predispose the fatty liver to develop progressive liver damage. Chief among the many mechanisms involved in development of hepatic steatosis is dysregulation of insulin-mediated adipose tissue metabolis...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109059
更新日期:2020-05-01 00:00:00
abstract::Iron and copper ions, in their unbound form, may lead to the generation of reactive oxygen species via Haber-Weiss and/or Fenton reactions. In addition, it has been shown that copper ions can irreversibly and non-specifically bind to thiol groups in proteins. This non-specific binding property has not been fully addre...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2010.06.013
更新日期:2010-10-06 00:00:00
abstract::Chrysophanol, a major anthraquinone component occurring in many traditional Chinese herbs, is accepted as important active component with various pharmacological actions such as antibacterial and anticancer activity. Previous studies demonstrated that exposure to chrysophanol induced cytotoxicity, but the mechanisms o...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2018.04.015
更新日期:2018-06-01 00:00:00
abstract::We have previously shown that subclinical hypervitaminosis A in rats causes fragile bones. To begin to investigate possible mechanisms for Vitamin A action we extended our previous study. Forty-five mature female Sprague-Dawley rats were divided into three groups, each with 15 animals. They were fed a standard diet co...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2005.10.104
更新日期:2006-01-05 00:00:00
abstract::Liquid-holding recovery and rejoining of gamma-radiation-induced DNA single-strand scissions in Escherichia coli could be effectively inhibited by procaine hydrochloride at the concentration of 20 mM. At this concentration, the drug also reversibly altered cellular permeability barrier as evidenced from the uptake of ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(75)90097-6
更新日期:1975-09-01 00:00:00
abstract::Esophageal squamous cell carcinoma (ESCC), the main subtype of esophageal cancer, is the eighth most common cancer worldwide. Cell adhesion molecule 2 (CADM2) has been reported to be a tumor suppressor and is usually downregulated in several cancers. However, the role of CADM2 in ESCC remains unknown. The aim of the p...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2018.04.021
更新日期:2018-05-25 00:00:00
abstract::In isolated frog heart it was established that methylene-blue (MB, an oxidizing agent) decreased, while ascorbate (ASC, a reducing agent) increased the frequency of autorhythmic heart contractions. After MB treatment, in parallel with this phenomenon, the extracellular K+ concentration [K+]o showed a slow increase, bu...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(87)90092-5
更新日期:1987-01-01 00:00:00
abstract::In recent years, attention has been focused on the anti-cancer properties of pure components, an important role in the prevention of disease. Andrographolide (Andro), the major constituent of Andrographis paniculata (Burm. F.) Nees plant, is implicated towards its pharmacological activity. To investigate the mechanism...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2008.06.006
更新日期:2008-08-11 00:00:00
abstract::Cholinesterases (ChEs) are classified as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) according to their substrate specificity and sensitivity to selected inhibitors. The activities of AChE in red blood cells (RBC-AChE) and BChE in serum can be used as potential biomarkers of suppressed and/or heighten...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2005.10.031
更新日期:2005-12-15 00:00:00