The Application of Embelin for Cancer Prevention and Therapy

Embelin is a naturally-occurring benzoquinone compound that has been shown to possess many biological properties relevant to human cancer prevention and treatment, and increasing evidence indicates that embelin may modulate various characteristic hallmarks of tumor cells. This review summarizes the information related to the various oncogenic pathways that mediate embelin-induced cell death in multiple cancer cells. The mechanisms of the action of embelin are numerous, and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and modulate the NF-κB, p53, PI3K/AKT, and STAT3 signaling pathways. Embelin also induces autophagy in cancer cells; however, these autophagic cell-death mechanisms of embelin have been less reported than the apoptotic ones. Recently, several autophagy-inducing agents have been used in the treatment of different human cancers, although they require further exploration before being transferred from the bench to the clinic. Therefore, embelin could be used as a potential agent for cancer therapy.

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

Journal of Biomedical Translational Research ◽

10.12729/jbtr.2020.21.2.050 ◽

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

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

Food & Function ◽

10.1039/c8fo00526e ◽

2018 ◽

Vol 9 (7) ◽

pp. 3895-3905 ◽

Cited By ~ 15

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.

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A Potential Antineoplastic Peptide of Human Prostate Cancer Cells Derived from the Lesser Spotted Dogfish (Scyliorhinus canicula L.)

Marine Drugs ◽

10.3390/md17100585 ◽

2019 ◽

Vol 17 (10) ◽

pp. 585 ◽

Cited By ~ 1

Author(s):

Adrien Bosseboeuf ◽

Amandine Baron ◽

Elise Duval ◽

Aude Gautier ◽

Pascal Sourdaine ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Cell Death ◽

Growth Inhibition ◽

Cancer Cells ◽

Apoptotic Cell ◽

Prostate Cancer Cells ◽

Cell Death Mechanisms ◽

Autophagy Inhibition

The purpose of the present paper is to investigate the mechanism of action of a pyroglutamate-modified peptide (pE-K092D) on in vitro growth inhibition of MDA-Pca-2b prostate cancer cells. This peptide was derived from a peptide previously isolated from the testis of the lesser spotted dogfish and identified as QLTPEALADEEEMNALAAR (K092D). The effect of the peptide on cell proliferation and cell death mechanisms was studied by flow cytometry. Cellular morphology and cytoskeleton integrity of peptide-treated cells were observed by immunofluorescence microscopy. Results showed the onset of peptide induced early cytoskeleton perturbation, inhibition of autophagy, inhibition of cell proliferation and, at the end, non-apoptotic cell death mechanisms (membrane destabilization and necrosis). All those mechanisms seem to contribute to MDA-Pca-2b growth inhibition by a main cytostatic fate.

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

Molecules ◽

10.3390/molecules24050977 ◽

2019 ◽

Vol 24 (5) ◽

pp. 977 ◽

Cited By ~ 7

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.

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Induction of Apoptotic Cell Death Specifically in Rat and Human Cancer Cells by Pancratistatin

Artificial Cells Blood Substitutes and Biotechnology ◽

10.1081/bio-200066621 ◽

2005 ◽

Vol 33 (3) ◽

pp. 279-295 ◽

Cited By ~ 24

Author(s):

Siyaram Pandey ◽

Natasha Kekre ◽

Jafar Naderi ◽

James McNulty

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Apoptotic Cell ◽

Human Cancer ◽

Apoptotic Cell Death ◽

Human Cancer Cells

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

International Journal of Molecular Sciences ◽

10.3390/ijms20163953 ◽

2019 ◽

Vol 20 (16) ◽

pp. 3953 ◽

Cited By ~ 4

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.

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

Molecules ◽

10.3390/molecules23081849 ◽

2018 ◽

Vol 23 (8) ◽

pp. 1849 ◽

Cited By ~ 7

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.

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Clioquinol targets zinc to lysosomes in human cancer cells

Biochemical Journal ◽

10.1042/bj20081421 ◽

2008 ◽

Vol 417 (1) ◽

pp. 133-139 ◽

Cited By ~ 70

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.

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K092A and K092B, Two Peptides Isolated from the Dogfish (Scyliorhinus canicula L.), with Potential Antineoplastic Activity Against Human Prostate and Breast Cancer Cells

Marine Drugs ◽

10.3390/md17120672 ◽

2019 ◽

Vol 17 (12) ◽

pp. 672 ◽

Cited By ~ 1

Author(s):

Adrien Bosseboeuf ◽

Amandine Baron ◽

Elise Duval ◽

Aude Gautier ◽

Pascal Sourdaine ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Apoptotic Cell ◽

Antineoplastic Activity ◽

Human Prostate ◽

Scyliorhinus Canicula ◽

Cell Death Mechanisms

Cancer therapy is currently a major challenge within the research community, especially in reducing the side effects of treatments and to develop new specific strategies against cancers that still have a poor prognosis. In this context, alternative strategies using biotechnologies, such as marine peptides, have been developed based on their promise of effectivity associated with a low toxicity for healthy cells. The purpose of the present paper is to investigate the active mechanism of two peptides that were isolated from the epigonal tissue of the lesser spotted dogfish Scyliorhinus canicula L., identified NFDTDEQALEDVFSKYG (K092A) and EAPPEAAEEDEW (K092B) on the in vitro growth inhibition of ZR-75-1 mammary carcinoma cells and MDA-Pca-2b prostate cancer cells. The effects of the peptides on cell proliferation and cell death mechanisms were studied by the flow cytometry and immunofluorescence microscopy approaches. The results have shown the onset of both K092A- and K092B-induced early cytoskeleton changes, and then cell cycle perturbations followed by non-apoptotic cell death. Moreover, impedance perturbation and plasma membrane perforation in ZR-75-1 K092A-treated cell cultures and autophagy inhibition in MDA-Pca-2b K092B-treated cells have been observed. In conclusion, these two bioactive peptides from dogfish exhibit antineoplastic activity on the human prostate and breast cancer cells in vitro.

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