Clioquinol targets zinc to lysosomes in human cancer cells

2008 ◽  
Vol 417 (1) ◽  
pp. 133-139 ◽  
Author(s):  
Haijun Yu ◽  
Yunfeng Zhou ◽  
Stuart E. Lind ◽  
Wei-Qun Ding
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Apoptotic Cell Death ◽  
Cellular Targets ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Free Zinc ◽  
Cancer Line

We have previously demonstrated that clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) acts as a zinc ionophore and induces apoptosis of human cancer cells; however, the mechanisms of clioquinol/zinc-induced apoptotic cell death remain to be elucidated further. Using fluorescence-labelled probes, the present study has examined intracellular zinc distribution after clioquinol treatment in human cancer cells in order to identify cellular targets for zinc ionophores. DU 145, a human prostate cancer line, was chosen as a model system for the present study, and results were confirmed in other human cancer cell lines. Although treatment of cancer cells with 50 μM ZnCl2 for 3 days had no effect on cell viability, addition of clioquinol dramatically enhanced the cytotoxicity, confirming our previous observations. The ionophore activity of clioquinol was confirmed using fluorescence microscopy. Intracellular free zinc was found to be concentrated in lysosomes, indicating that lysosomes are the primary target of zinc ionophores. Furthermore, lysosomal integrity was disrupted after addition of clioquinol and zinc to the cells, as shown by redistribution of both Acridine Orange and cathepsin D. Clioquinol plus zinc resulted in a cleavage of Bid (BH3-interacting domain death agonist), a hallmark of lysosome-mediated apoptotic cell death. Thus the present study demonstrates for the first time that clioquinol generates free zinc in lysosomes, leading to their disruption and apoptotic cell death.

scholarly journals Flavonoid-induced apoptotic cell death in human cancer cells and its mechanisms

2020 ◽  
Vol 21 (2) ◽  
pp. 50-58
Author(s):  
Pritam Bhagwan Bhosale ◽  
Sang Eun Ha ◽  
Preethi Vetrivel ◽  
Hun Hwan Kim ◽  
Jin-A Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Apoptotic Cell Death ◽  
Human Cancer Cells

Triterpenoids fromZiziphus jujubainduce apoptotic cell death in human cancer cells through mitochondrial reactive oxygen species production

2018 ◽  
Vol 9 (7) ◽  
pp. 3895-3905 ◽  
Author(s):  
Minna Shin ◽  
Bo-Mi Lee ◽  
Okwha Kim ◽  
Huynh Nguyen Khanh Tran ◽  
Suhyun Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Apoptotic Cell Death ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Human Cancer Cells ◽  
Mitochondrial Ros ◽  
Species Production

Coumaroyl alphitolic acids induce apoptotic cell death in cancer cellsviamitochondrial ROS production and ER stress.

scholarly journals Identification and Characterization of the Caspase-Mediated Apoptotic Activity of Teucrium mascatense and an Isolated Compound in Human Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 977 ◽  
Author(s):  
Neena Panicker ◽  
Sameera Balhamar ◽  
Shaima Akhlaq ◽  
Mohammed Qureshi ◽  
Tania Rizvi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Annexin V ◽  
Dependent Manner ◽  
Human Cancer Cells ◽  
Cell Death Pathways ◽  
Proliferative Effect ◽  
Mcf 7

Plants of the genus Teucrium (Lamiaceae or Labiatae family) are known historically for their medicinal value. Here, we identify and characterize the anticancer potential of T. mascatense and its active compound, IM60, in human cancer cells. The anti-proliferative effect of a T. mascatense methanol extract and its various fractions were analyzed in MCF-7 and HeLa cells in a dose- and time dependent manner. The dichloromethane fraction (TMDF) was observed to be the most effective with cytotoxicity against a more expanded series of cell lines, including MDA-MB-231. A time and dose-dependent toxicity profile was also observed for IM60; it could induce rapid cell death (within 3 h) in MCF-7 cells. Activation of caspases and PARP, hallmarks of apoptotic cell death pathways, following treatment with TMDF was demonstrated using western blot analysis. Inversion of the phosphatidylserine phospholipid from the inner to the outer membrane was confirmed by annexin V staining that was inhibited by the classical apoptosis inhibitor, Z-VAK-FMK. Changes in cell rounding, shrinkage, and detachment from other cells following treatment with TMDF and IM60 also supported these findings. Finally, the potential of TMDF and IM60 to induce enzymatic activity of caspases was also demonstrated in MCF-7 cells. This study, thus, not only characterizes the anticancer potential of T. mascatense, but also identifies a lead terpenoid, IM60, with the potential to activate anticancer cell death pathways in human cancer cells.

scholarly journals Goniothalamin Induces Necroptosis and Anoikis in Human Invasive Breast Cancer MDA-MB-231 Cells

2019 ◽  
Vol 20 (16) ◽  
pp. 3953 ◽  
Author(s):  
Patompong Khaw-on ◽  
Wilart Pompimon ◽  
Ratana Banjerdpongchai
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Apoptotic Cell Death ◽  
Human Breast ◽  
Mesenchymal Transition

Goniothalamin (GTN) is toxic to several types of cancer cells in vitro. However, its effects on non-apoptotic cell death induction of human cancer cells have been poorly documented. Here, an investigation of the anti-cancer activity of GTN and the molecular signaling pathways of non-apoptotic cell death in the invasive human breast cancer MDA-MB-231 cell line were undertaken. Apoptotic cell death was suppressed by using a pan-caspase inhibitor (Benzyloxycarbonyl-Val-Ala-Asp-[O-methyl]-fluoromethylketone), z-VAD-fmk) as a model to study whether GTN induced caspase-independent cell death. In the anoikis study, MDA-MB-231 cells were cultured on poly-(2-hydroxyethyl methacrylate)- or poly-HEMA- coated plates to mimic anoikis-resistance growth and determine whether GTN induced cell death and the mechanisms involved. GTN and z-VAD-fmk induced human breast cancer MDA-MB-231 cells to undergo necroptosis via endoplasmic reticulum (ER) and oxidative stresses, with increased expressions of necroptotic genes such as rip1, rip3, and mlkl. GTN induced MDA-MB-231 cells to undergo anoikis via reversed epithelial-mesenchymal transition (EMT) protein expressions, inhibited the EGFR/FAK/Src survival signaling pathway, and decreased matrix metalloproteinase secretion.

scholarly journals (−)-Asarinin from the Roots of Asarum sieboldii Induces Apoptotic Cell Death via Caspase Activation in Human Ovarian Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1849 ◽  
Author(s):  
Miran Jeong ◽  
Hye Kim ◽  
Jin Lee ◽  
Jung-Hye Choi ◽  
Dae Jang
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Apoptotic Cell Death ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Chemical Structures ◽  
Skov3 Cells

Two tetrahydrofurofurano lignans (1 and 2), four phenylpropanoids (3–6), and two alkamides (7 and 8) were isolated from the EtOAc-soluble fraction of the roots of Asarum sieboldii. The chemical structures of the isolates were identified by analysis of spectroscopic data measurements, and by a comparison of their data with published values. The isolates (1, 2, 4–8) were evaluated for their cytotoxicity against human ovarian cancer cells (A2780 and SKOV3) and immortalized ovarian surface epithelial cells (IOSE80PC) using a MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. Of the isolates, (−)-asarinin (1) exhibited the most potent cytotoxicity to both A2780 and SKOV3 cells. A propidium iodide/annexin V-fluorescein isothiocyanate (V-FITC) double staining assay showed that (−)-asarinin (1) induces apoptotic cell death in ovarian cancer cells. In addition, (−)-asarinin (1) increased the activation of caspase-3, caspase-8, and caspase-9 in ovarian cancer cells. Pretreatment with caspase inhibitors attenuated the cell death induced by (−)-asarinin (1). In conclusion, our findings show that (−)-asarinin (1) from the roots of A. sieboldii may induce caspase-dependent apoptotic cell death in human cancer cells.

scholarly journals Inducing oncolytic cell death in human cancer cells by the long non-coding RNA let-A

2021 ◽  
Author(s):  
Tosca Birbaumer ◽  
Tommy Beat Schlumpf ◽  
Makiko Seimiya ◽  
Yanrui Jiang ◽  
Renato Paro
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cell Lines ◽  
Human Cancer ◽  
Ectopic Expression ◽  
In Vitro Transcription ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Non Coding Rna

Long non-coding (lnc) RNAs contain functional elements that play important regulatory roles in a variety of processes during development, normal physiology, as well as disease. We recently discovered a new lncRNA, we named let-A, expressed from the evolutionary conserved let-7-Complex locus in Drosophila. This RNA induces cell death in Drosophila cancer cells. Here we show that ectopic expression of Drosophila let-A is also exerting an oncolytic toxicity in several human cancer cell lines, but shows almost no effect in more differentiated or cell lines derived from normal tissue. We demonstrate that let-A RNA prepared by in vitro transcription and provided in the growth medium is sufficient to induce cell death both in human and Drosophila cancer cells. The activity of in vitro transcribed let-A is most efficient in its full length, but requires prior modification/processing to become active. let-A induces a reduction of nucleolar size in treated cells. We show exo/endocytosis and Toll signaling pathway to be necessary for let-A-induced toxicity. Our findings indicate let-A exhibits an evolutionary conserved anti-cancer function, making it a promising molecule for tumor treatments.

scholarly journals Induction of a Non‐Apoptotic Cell Death in Momordica Charantia ‐Treated Human Cancer Cell Lines

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Adeola Folasade Ehigie ◽  
Peng Wei ◽  
Taotao Wei ◽  
Leonard Ona Ehigie ◽  
Xiyun Yan ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Momordica Charantia ◽  
Apoptotic Cell Death ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines
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