β-elemene reverses the drug resistance of A549/DDP lung cancer cells by activating intracellular redox system, decreasing mitochondrial membrane potential and P-glycoprotein expression, and inducing apoptosis

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a Chinese herbal anthraquinone that exhibits numerous biological activities, such as antitumor, antibacterial, antiinflammatory, and immunosuppressive. From an endophytic fungus, a close relative of Polyporales sp., found in association with Rheum emodi, Wall. ex Meissn a compound (Rz) was isolated and characterizedby different spectroscopic techniques (1H-NMR, 13CNMR, 2D-NMR, and HRMS). The compound (Rz) displayed a range of cytotoxicities against different human cancer cell lines like THP-1(Leukemia), A549 (Lung), NCI-H322 (lung) and Colo-205(colon) at a concentration of 70 and 100 µM. The compound had strong anticancer activity by arresting the cell cycle at G1 and G2/M phase and loss of mitochondrial membrane potential in A-549 lung cancer cells in concentration dependent manner. The study suggests that emodin induced anticancer effects may have novel therapeutic applications for the treatment of lung cancer.

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Artesunate inhibits lung cancer cells via regulation of mitochondrial membrane potential and induction of apoptosis

Molecular Medicine Reports ◽

10.3892/mmr.2020.11341 ◽

2020 ◽

Author(s):

Yan Zhao ◽

Jianghui Liu ◽

Liang Liu

Keyword(s):

Lung Cancer ◽

Membrane Potential ◽

Cancer Cells ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Lung Cancer Cells ◽

Induction Of Apoptosis

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Ophiopogonin B-inducing Pyroptosis Through Caspase-1/gsdmd Pathway Contributes to Alleviation of Paclitaxel Resistance in Lung Cancer Cells

10.21203/rs.3.rs-100288/v1 ◽

2020 ◽

Author(s):

Ziyu Cheng ◽

Zhihui Li ◽

Ling Gu ◽

Liqiu Li ◽

Qian Gao ◽

...

Keyword(s):

Lung Cancer ◽

Drug Resistance ◽

Membrane Potential ◽

Cancer Cells ◽

Mitochondrial Membrane Potential ◽

Nude Mice ◽

Release Rate ◽

Mitochondrial Membrane ◽

A549 Cells ◽

Caspase 1

Abstract Background: Drug resistance has become the main reason for the failure of tumor chemotherapy. In our previous study, ophiopogonin B (OP-B) has been verified to inhibit cell proliferation in numerous non-small cell lung cancer (NSCLC) cells. However, it is still unknown whether it can improve the drug resistance of lung cancer cells. Herein, we compared the inhibition effects of OP-B on NCI-H460, A549, A549/DDP and A549/PTX cells, and tried to find out the most sensible cell line to OP-B and the underlying reasons. Methods: The sensitivity of NCI-H460, A549, A549/DDP, and A549/PTX cells to OP-B was determined by CCK-8 assay, and the results were further verified in orthotopic tumor nude mice model and zebrafish tumor model. To identify pyroptosis in the cells, electron microscopy was used to observe cell morphology, flow cytometry was used to detect the mitochondrial membrane potential, and the LDH release rate was analyzed by microplate reader. Otherwise, immunofluorescence and immunohistochemical staining assay, western blot and qRT-PCR were used for detection of pyroptosis-correlated pathway.Results: In vitro, A549/DDP cell was verified to be most sensitive to OP-B than NCI-H460, A549, or A549/PTX cells. In vivo, OP-B inhibited the growth of A549/DDP orthotopic tumor more significantly than that of A549 both in nude mice and zebrafish models. Cell morphological feature, mitochondrial membrane potential, LDH release rate, production of IL-1β and expression of Caspase-1/GSDMD all showed that pyroptosis happened more significantly in A549/DDP cells than that in A549 cells after OP-B treatment.Conclusion: Though inducing more significantly pyroptosis by activating Caspase-1/GSDMD pathway, OP-B relieved DDP resistance of A549 cells.

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Grape Proanthocyanidins Induce Apoptosis by Loss of Mitochondrial Membrane Potential of Human Non-Small Cell Lung Cancer Cells In Vitro and In Vivo

PLoS ONE ◽

10.1371/journal.pone.0027444 ◽

2011 ◽

Vol 6 (11) ◽

pp. e27444 ◽

Cited By ~ 62

Author(s):

Tripti Singh ◽

Som D. Sharma ◽

Santosh K. Katiyar

Keyword(s):

Lung Cancer ◽

Membrane Potential ◽

Small Cell Lung Cancer ◽

Cancer Cells ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Small Cell ◽

Small Cell Lung

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Correction: Grape Proanthocyanidins Induce Apoptosis by Loss of Mitochondrial Membrane Potential of Human Non-Small Cell Lung Cancer Cells In Vitro and In Vivo

PLoS ONE ◽

10.1371/annotation/23a8e553-4fce-4c73-9946-7a2a6a5729e9 ◽

2012 ◽

Vol 7 (6) ◽

Cited By ~ 4

Author(s):

Tripti Singh ◽

Som D. Sharma ◽

Santosh K. Katiyar

Keyword(s):

Lung Cancer ◽

Membrane Potential ◽

Small Cell Lung Cancer ◽

Cancer Cells ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Small Cell ◽

Small Cell Lung

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Maintenance of Respiration Capacity Is an Early Predictor of Drug Resistance in Cancer Cells

Blood ◽

10.1182/blood.v124.21.2157.2157 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2157-2157

Author(s):

Cornelia A Brendel ◽

Katharina Henkenius ◽

Melanie Maerken ◽

Tom Kaiser ◽

Larissa Greif ◽

...

Keyword(s):

Drug Resistance ◽

Membrane Potential ◽

Cancer Therapy ◽

Cancer Cells ◽

Mitochondrial Membrane Potential ◽

Mtt Assay ◽

Mitochondrial Function ◽

Mitochondrial Membrane ◽

Drug Exposure ◽

Cellular Respiration

Abstract Inherent or acquired drug resistance is the major obstacle in cancer therapy. An individual prediction of response to cancer therapy would be highly appreciated. It has been reported that the mitochondrial function of cancer cells correlates with the treatment response in different cancer entities (Chonghaile et al., Science 2011 and Vo et al., Cell 2012). However, as the method of BCL-2 peptide priming measurement (“BH3 profiling”) seemed to be rather complicated and error-prone in our hand we sought to determine mitochondrial function by analyzing cellular respiration. We established three different drug resistant human cancer cell lines (MV4-11, HL-60 and NCl-H82) by continuous exposure to Sorafenib, Cytarabine (Ara-C) or Etoposid (VP-16) respectively. Cellular respiration was measured as oxygen consumption rate (OCR) 24h after drug exposure employing the XF96 extracellular Flux Analyzer. Viability, reduction equivalents NADH/NADPH and mitochondrial membrane potential of the cells were concomitantly determined by flow cytometry via 4’, 6-diamidino-2-phenylindole (DAPI) exclusion, (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Tetramethylrhodamine ethyl ester (TMRE) staining with flow cytometric analysis, respectively. All resistant cancer cells maintained their respiration capacity upon exposure to tyrosine kinase inhibitors, chemotherapeutics or topoisomerase inhibitors, whereas the respiration of drug sensitive cancer cells decreased significantly. Moreover, resistant MV4-11 and HL-60 cells exhibited a metabolic shift towards glycolysis after drug treatment. In contrast sensitive cancer cells showed a decline in respiration and glycolysis in a dose dependent manner. Decrease of respiration was evident at 24h post treatment, while the onset of apoptosis was measurable 48-120h later. Reduction equivalents NADH/NADPH but not mitochondrial membrane potential were diminished in sensitive cells after 24h drug exposure, but dose dependency was more distinct with OCR analysis. The increase of glycolysis in resistant cell lines was also not detectable with the MTT assay. Our data indicate cellular metabolism and in particular respiration as an early, sensitive and reliable surrogate parameter of drug sensitivity in viable cells that might therefore be applicable in order to determine drug responsiveness in primary cancer cells in a prospective manner. Disclosures No relevant conflicts of interest to declare.

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SP1 Mediates MRP1 Upregulation and Multi-Drug Resistance in Human Lung Cancer Cells

SSRN Electronic Journal ◽

10.2139/ssrn.3427292 ◽

2019 ◽

Author(s):

Shuli Shao ◽

Yunjianan Feng ◽

Yue Xiao ◽

Yan Li ◽

Weiwei Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Drug Resistance ◽

Cancer Cells ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Multi Drug Resistance ◽

Human Lung Cancer Cells

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Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180209152215 ◽

2019 ◽

Vol 18 (9) ◽

pp. 1313-1322 ◽

Cited By ~ 5

Author(s):

Manjula Devi Ramamoorthy ◽

Ashok Kumar ◽

Mahesh Ayyavu ◽

Kannan Narayanan Dhiraviam

Keyword(s):

Prostate Cancer ◽

Reactive Oxygen Species ◽

Cell Cycle ◽

Membrane Potential ◽

Cancer Cells ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Reactive Oxygen ◽

Oxygen Species ◽

Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

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