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Cancer Chemotherapy and Pharmacology

Published in:

01-04-2011 | Original Article

Solamargine, a steroidal alkaloid glycoside, induces oncosis in human K562 leukemia and squamous cell carcinoma KB cells

Authors: Lingmei Sun, Ying Zhao, Huiqing Yuan, Xia Li, Aixia Cheng, Hongxiang Lou

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2011

Abstract

Purpose

The aim of this study was to demonstrate that solamargine (SM) mediates its cytotoxicity via oncosis.

Methods

The cytotoxicity of SM on cancer cells was examined by 3-(4,5-dimethylthiazol)-2 and 5-diphenyltetrazolium bromide assay. Cell membrane integrity was assessed by detecting the leakage of cytoplasmic content, the release of lactate dehydrogenase (LDH), and the uptake of propidium iodide (PI). We use whole-cell recording to measure the time courses of membrane blebbing and disruption in human K562 leukemia and squamous cell carcinoma KB cells. The effects of SM on cytoskeletal systems were detected by Western blotting and immunofluorescence.

Results

The cytotoxicity of SM did not correlate with the expression level of the multidrug resistance MDR1 and was triggered rapidly by 10 μM SM (5 min caused 50% maximum cytotoxicity). Its rapid ability to make propidium iodide (PI) permeate into tumor cells, LDH release, and leakage of cytoplasmic content at the same rate (within minutes), suggests a killing mechanism that involves plasma membrane perturbation. SM induced membrane blebbing within 5 min of sustained application. Both chelating extracellular calcium with EGTA and clamping intracellular calcium concentrations with a high concentration of the cell-permeable chelator BAPTA-AM did not prevent blebbing. Polyethylene glycols having molecular weights ≥3,350 blocked membrane blebbing. SM also disrupted the cytoskeletal systems: degradation of microtubules and actin proteins.

Conclusion

SM can rapidly initiate acute injury and bursting by damaging to cellular membrane and may offer a novel therapeutic strategy in treatment of cancer.

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Title: Solamargine, a steroidal alkaloid glycoside, induces oncosis in human K562 leukemia and squamous cell carcinoma KB cells
Authors: Lingmei Sun
Ying Zhao
Huiqing Yuan
Xia Li
Aixia Cheng
Hongxiang Lou
Publication date: 01-04-2011
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-010-1387-9

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Abstract

Purpose

Methods

Results

Conclusion

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