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 Effect of Calomelanone, a Dihydrochalcone Analogue, on Human Cancer Apoptosis/Regulated Cell Death in an In Vitro Model

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Wasitta Rachakhom ◽  
Ratana Banjerdpongchai
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Cytotoxic Effect ◽  
Human Cancer ◽  
Autophagic Flux ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Human Cancer Cells ◽  
Regulated Cell Death

Calomelanone, 2 ′ ,6 ′ -dihydroxy-4,4 ′ -dimethoxydihydrochalcone, possesses anticancer activities. This study was conducted to investigate the cytotoxic effect of calomelanone, a dihydrochalcone analogue, on human cancer cells and its associated mechanisms. The cytotoxic effect of calomelanone was measured by MTT assay. Annexin V-FITC/propidium iodide and DiOC6 staining that employed flow cytometry were used to determine the mode of cell death and reduction of mitochondrial transmembrane potential (MTP), respectively. Caspase activities were measured using specific substrates and colorimetric analysis. The expression levels of Bcl-2 family proteins were determined by immunoblotting. Reactive oxygen species were also measured using 2 ′ ,7 ′ -dihydrodichlorofluorescein diacetate and dihydroethidium (fluorescence dyes). Calomelanone was found to be toxic towards various human cancer cells, including acute promyelocytic HL-60 and monocytic leukemic U937 cells, in a dose-dependent manner at 24 h and human hepatocellular HepG2 cells at 48 h. However, the proliferation of HepG2 cells increased at 24 h. Calomelanone was found to induce apoptosis in HL-60 and U937 at 24 h and HepG2 apoptosis at 48 h via the intrinsic pathway by inducing MTP disruption. This compound also induced caspase-3, caspase-8, and caspase-9 activities. Calomelanone upregulated proapoptotic Bax and Bak and downregulated antiapoptotic Bcl-xL proteins in HepG2 cells. Moreover, signaling was also associated with oxidative stress in HepG2 cells. Calomelanone induced autophagy at 24 h of treatment, which was evidenced by staining with monodansylcadaverine (MDC) to represent autophagic flux. This was associated with a decrease of Akt (survival pathway) and an upregulation of Atg5 (the marker of autophagy). Thus, calomelanone induced apoptosis/regulated cell death in HL-60, U937, and HepG2 cells. However, it also induced autophagy in HepG2 depending on duration, dose, and type of cells. Thus, calomelanone could be used as a potential anticancer agent for cancer treatment. Nevertheless, acute and chronic toxicity should be further investigated in animals before conducting investigations in human patients.

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.

Cudraxanthone H Induces Growth Inhibition and Apoptosis in Oral Cancer Cells via NF-κB and PIN1 Pathways

2015 ◽  
Vol 43 (07) ◽  
pp. 1439-1452 ◽  
Author(s):  
Hwa-Jeong Lee ◽  
Seong-Suk Jue ◽  
Soo-Kyung Kang ◽  
Won-Jung Bae ◽  
Youn-Chul Kim ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Kinase Inhibitor ◽  
Human Cancer ◽  
Annexin V ◽  
Root Bark ◽  
Dependent Manner ◽  
Human Cancer Cells ◽  
Induced Apoptosis

Cudraxanthone H (CH) is a natural compound isolated from a methanol extract of the root bark of Cudrania tricuspidata, a herbal plant also known as Moraceae. However, the effect of CH on human cancer cells has not been reported previously. The aim of this study was to investigate the anticancer effects and mechanism of action of CH on oral squamous cell carcinoma (OSCC) cells. CH exerted significant antiproliferative effects on OSCC cells in dose- and time-dependent manners. CH also induced apoptosis in OSCC cells, as evidenced by an increased percentage of cells in the sub-G1 phase of the cell cycle, annexin V-positive/propidium iodide-negative cells, and nuclear morphology. This antiproliferative effect of CH was associated with a marked reduction in the expression of cyclin D1 and cyclin E, with a concomitant induction of cyclin-dependent kinase inhibitor (CDKI) expression (p21 and p27). CH inhibited the phosphorylation and degradation of I[Formula: see text]B-[Formula: see text]and the nuclear translocation of NF-[Formula: see text]B p65. Furthermore, CH treatment down-regulated PIN1 mRNA and protein expression in a dose-dependent manner. PIN1 overexpression by infection with adenovirus-PIN1 (Ad-PIN1) attenuated the CH-induced growth-inhibiting and apoptosis-inducing effects, blocked CH-enhanced CDKI expression and restored cyclin levels. In contrast, inhibiting PIN1 expression via juglone exerted the opposite effects. The present study is the first to demonstrate antiproliferative and apoptosis-inducing effects of CH, which exerts its effects by inhibiting NF-[Formula: see text]B and PIN1. These data suggest that it might be a novel alternative chemotherapeutic agent for use in the treatment of oral cancer.

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.

Antiproliferative effect of β-escin - an in vitro study.

2016 ◽  
Vol 63 (1) ◽  
Author(s):  
Gabriela Mojžišová ◽  
Martin Kello ◽  
Martina Pilátová ◽  
Vladimíra Tomečková ◽  
Janka Vašková ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Mitochondrial Protein ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
In Vitro Study ◽  
Dependent Manner ◽  
Human Cancer Cells ◽  
Apoptotic Effects

This study examined the antiproliferative effects of β-escin (E) in cancer cells. The study showed that E inhibited cancer cells growth in a dose-dependent manner. The flow cytometric analysis revealed an escin-induced increase in the sub-G1 DNA content, which is considered to be a marker of apoptosis. Apoptosis was also confirmed by annexin V staining and DNA fragmentation assay. These effects were associated with increased generation of reactive oxygen species (ROS), caspase-3 activation and decreased mitochondrial membrane potential (MMP). Moreover, escin decreased mitochondrial protein content and mitochondrial fluorescence intensity as well as caused depletion of glutathione (GSH). However, activity of glutathione peroxidase (GPx) and glutathione reductase (GR) was not significantly changed in escin-treated cells. In conclusion, our results demonstrated that E has apoptotic effects in human cancer cells through the mechanisms involving mitochondrial perturbation. Although the exact mechanism needs to be investigated further, it can be concluded that E may be a useful candidate agent for cancer treatment.

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