The study of sclareol in inhibiting proliferation of osteosarcoma cells by apoptotic induction and loss of mitochondrial membrane potential

2018 ◽  
Vol 22 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Guoqing Duan ◽  
Su Hou ◽  
Jianjun Ji ◽  
Bin Deng
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Osteosarcoma Cells ◽  
Apoptotic Induction

Spontaneous mitochondrial membrane potential change during apoptotic induction by quercetin in K562 and K562/adr cells

2004 ◽  
Vol 82 (12) ◽  
pp. 1084-1090 ◽  
Author(s):  
S Kothan ◽  
S Dechsupa ◽  
G Leger ◽  
J L Moretti ◽  
J Vergote ◽  
...  
Keyword(s):  
Cell Death ◽  
Natural Products ◽  
Multidrug Resistance ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Annexin V ◽  
Cancer Treatments ◽  
Membrane Potential Change ◽  
Apoptotic Induction

Natural products from plants such as flavonoids are potential drugs to overcome multidrug resistance (MDR) in cancer treatments. However, their modes of action are still unclear. In this study, the effects of quercetin on mitochondrial membrane potential (ΔΨm) change as well as quercetin's ability to induce apoptosis and inhibit Pgp-mediated efflux of 99mTc-MIBI in K562/adr cells were investigated. Quercetin exhibits cytotoxicity against erythroleukemic cells: IC50 are 11.0 ± 2.0 µmol/L and 5.0 ± 0.4 µmol/L for K562 and K562/adr, respectively. Quercetin induces cell death via apoptosis in both K562 and K562/adr cells and does not inhibit Pgp-mediated efflux of 99mTc-MIBI. Quercetin (10 µmol/L, 3 h) and etoposide (100 µmol/L, 24 h) induce similar levels of apoptosis in K562 and K562/adr cells. Quercetin induces an increase followed by a decrease in |ΔΨm| value depending on its concentration. A decrease in the |ΔΨm| value is associated with an increase in the percentage of early apoptotic cells. It is clearly shown that quercetin results in a spontaneous ΔΨm change during apoptotic induction. Therefore, quercetin is potentially an apoptotic-inducing agent, which reacts at the mitochondrial level.Key words: multidrug resistance (MDR), quercetin, apoptosis, 99mTc-Annexin V, mitochondrial membrane potential (ΔΨm), 99mTc-MIBI.

Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction

2020 ◽  
Author(s):  
Yingpinyapat Kittirat ◽  
Jutarop Phetcharaburanin ◽  
Bundit Promraksa ◽  
Thanaporn Kultawatsiri ◽  
Arporn Wangwiwatsin ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cell Viability ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Apoptotic Cell ◽  
Atp Production ◽  
Lipid Species ◽  
Anti Cancer ◽  
Apoptotic Induction ◽  
Pyrvinium Pamoate

Abstract Pyrvinium pamoate (PP), an FDA-approved anthelmintic drug, has been validated as a highly potent anti-cancer agent. PP inhibits several crucial functions of cancer cells, and it has been patented recently as a potential chemotherapeutic drug for various cancers. The current study investigated the ability of PP in anti-proliferative activity and focused on the lipidomic profiles revealing the alteration of specific lipid species in cholangiocarcinoma (CCA) cells. PP inhibited CCA cell viability by suppressing mitochondrial membrane potential (MMP) and ATP production, leading to apoptotic cell death. Liquid chromatography-mass spectrometry combined with multivariate statistical analysis were performed to investigate lipid alteration of PP-induced apoptosis in CCA cells. The lipidomic analyses showed the altered lipid signatures of CCA cell types including S-acetyldihydrolipoamide, methylselenopyruvate and triglycerides that were increased in PP-treated CCA cells. In contrast, the levels of sphinganine and phosphatidylinositol were lower in the PP-treated group compared with its counterpart. Moreover, the orthogonal partial-least squares for regression analysis revealed that PP-induced MMP dysfunction, leading to inhibition of ATP contents, was significantly associated with triglyceride production, a characteristic of apoptotic cells. These alterations indicated that PP could suppress the MMP function, which caused inhibition of CCA cell viability through apoptotic induction resulting in lipid accumulation in CCA cells. These findings can provide new insight on an anti-cancer mechanism of PP under apoptotic induction ability that could be a promising therapeutic strategy for CCA treatment.

scholarly journals Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction

2021 ◽  
Vol 9 ◽  
Author(s):  
Yingpinyapat Kittirat ◽  
Jutarop Phetcharaburanin ◽  
Bundit Promraksa ◽  
Thanaporn Kulthawatsiri ◽  
Arporn Wangwiwatsin ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cell Viability ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Apoptotic Cell ◽  
Lipid Production ◽  
Lipid Species ◽  
Anti Cancer ◽  
Apoptotic Induction ◽  
Pyrvinium Pamoate

Pyrvinium pamoate (PP), an FDA-approved anthelmintic drug, has been validated as a highly potent anti-cancer agent and patented recently as a potential chemotherapeutic drug for various cancers. The aims of this study were, therefore, to investigate the ability of PP in anti-proliferative activity and focused on the lipid profiles revealing the alteration of specific lipid species in the liver fluke Opisthorchis viverrini (Ov)-associated cholangiocarcinoma (CCA) cells. PP inhibited CCA cell viability through suppressing mitochondrial membrane potential (MMP) and ATP productions, leading to apoptotic cell death. Liquid chromatography-mass spectrometry combined with chemometrics was performed to investigate lipid alteration during PP-induced apoptosis. The lipidomic analyses showed the altered lipid signatures of CCA cell types including S-acetyldihydrolipoamide, methylselenopyruvate, and triglycerides that were increased in PP-treated CCA cells. In contrast, the levels of sphinganine and phosphatidylinositol were lower in the PP-treated group compared with its counterpart. The orthogonal partial-least squares regression analysis revealed that PP-induced MMP dysfunction, leading to remarkably reduced ATP level, was significantly associated with triglyceride (TG) accumulation observed in PP-treated CCA cells. Our findings indicate that PP could suppress the MMP function, which causes inhibition of CCA cell viability through lipid production, resulting in apoptotic induction in CCA cells. These findings provide an anti-cancer mechanism of PP under apoptotic induction ability that may serve as the alternative approach for CCA treatment.

Platelets apoptosis in rats after global brain ischemia

2018 ◽  
pp. 27-35
Author(s):  
А.А. Соколовская ◽  
Э.Д. Вирюс ◽  
В.В. Александрин ◽  
А.С. Роткина ◽  
К.А. Никифорова ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Ischemic Stroke ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Brain Ischemia ◽  
Mitochondrial Membrane ◽  
Male Rats ◽  
Global Brain Ischemia ◽  
Platelet Apoptosis ◽  
Global Brain

Цель исследования. Ишемические повреждения головного мозга, являются одной из наиболее частой причин инвалидности и смертности во всем мире. Недавно была установлена роль апоптоза тромбоцитов в патофизиологии инсульта, однако его механизмы до сих пор остаются невыясненными. Несмотря на различные экспериментальные модели, направленные на мониторинг апоптоза тромбоцитов, результаты, относительно изучения и выявления апоптоза тромбоцитов при ишемии головного мозга у крыс, весьма немногочисленны. Цель исследования - анализ апоптоза тромбоцитов с помощью метода проточной цитофлуориметрии на модели глобальной ишемии мозга у крыс. Методика. В экспериментах использовано 6 крыс-самцов Вистар в возрасте от 5 до 6 мес., разделенных на 2 группы: интактный контроль (К) и глобальная ишемия головного мозга. Модель глобальной ишемии головного мозга у крыс воспроизводилась путём билатеральной окклюзии общих сонных артерий на фоне гипотензии. Уровень системного артериального давления снижали посредством кровопотери до 40-45 мм рт. ст. Суспензию тромбоцитов крыс получали методом гельфильтрации с использованием сефарозы 2B. Для анализа экстернализации фосфатидилсерина (ФС) тромбоциты крыс инкубировали с Аннексином V-PE в связывающем буфере. Для оценки митохондриального мембранного потенциала (ММП) тромбоциты инкубировали с катионным красителем JC-1. После инкубации образцы немедленно анализировали на проточном цитофлуориметре FACSCalibur (Becton Dickinson, США). Результаты. Согласно полученным данным, экстернализация ФС на тромбоцитах крыс, перенесших инсульт, была значительно выше (53,45 ± 4,21%), чем в контрольной группе крыс (5,27 ± 2,40%). Данный эффект подтверждается выраженной деполяризацией митохондриальных мембран (DYm). После экспериментальной ишемии мозга почти 40% тромбоцитов было деполяризовано. Заключение. Использованный в работе подбор методов и маркеров обеспечивает понимание механизмов апоптоза тромбоцитов как в экспериментальных, так и в клинических условиях. Полученные данные позволяют сделать заключение, что апоптоз тромбоцитов является одним из факторов развития глобальной ишемии головного мозга у крыс. Результаты могут быть использованы для понимания механизмов, участвующих в развитии ишемического повреждения, что, в свою очередь, может быть использовано при разработке новых терапевтических стратегий. Aim. Stroke is one of the most common causes of disability and mortality worldwide. Multiple experimental models of stroke have focused on monitoring of platelet apoptosis. However, studies on and detection of platelet apoptosis in rats with ischemic stroke are very scarce. We investigated platelet apoptosis in rats with global brain ischemia using flow cytometry. Methods. Experiments were carried out on healthy, adult Wistar male rats weighing 300-350 g. The rats were divided into the following 2 groups: intact rats and rats with global brain ischemia. Global brain ischemia was induced by two-vessel (2-VO) carotid occlusion in combination with hypotension. Systemic blood pressure was reduced by 40-45 mm Hg by inducing haemorrhage. Platelets were isolated by gel filtration on Sepharose 2B. For evaluation of phosphatidylserine (PS) externalization, platelets were incubated with Annexin V-PE and analyzed on FACSCalibur (BD Biosciences). Mitochondrial membrane potential (DY) was measured during platelets apoptosis using JC-1, a mitochondrial membrane potential indicator. Platelets were analyzed by flow cytometry immediately after the incubation. Results. PS externalization on platelets was significantly greater after global brain ischemia (53.45 ± 4.21%) than in the control group (5.27 ± 2.40%). Pronounced depolarization of mitochondrial membrane potential (DYm) confirmed this finding. In the rat group with experimental brain ischemia, almost 40% (35.24 ± 5.21%) of platelets were depolarized. Conclusion. Our results provide insight into mechanisms involved in platelet apoptosis during ischemic stroke and can be used in further development of new therapeutic strategies.

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