Momordica charantiaExtract Induces Apoptosis in Human Cancer Cells through Caspase- and Mitochondria-Dependent Pathways

Plants are an invaluable source of potential new anti-cancer drugs.Momordica charantiais one of these plants with both edible and medical value and reported to exhibit anticancer activity. To explore the potential effectiveness ofMomordica charantia, methanol extract ofMomordica charantia(MCME) was used to evaluate the cytotoxic activity on four human cancer cell lines, Hone-1 nasopharyngeal carcinoma cells, AGS gastric adenocarcinoma cells, HCT-116 colorectal carcinoma cells, and CL1-0 lung adenocarcinoma cells, in this study. MCME showed cytotoxic activity towards all cancer cells tested, with the approximate IC50ranging from 0.25 to 0.35 mg/mL at 24 h. MCME induced cell death was found to be time-dependent in these cells. Apoptosis was demonstrated by DAPI staining and DNA fragmentation analysis using agarose gel electrophoresis. MCME activated caspase-3 and enhanced the cleavage of downstream DFF45 and PARP, subsequently leading to DNA fragmentation and nuclear condensation. The apoptogenic protein, Bax, was increased, whereas Bcl-2 was decreased after treating for 24 h in all cancer cells, indicating the involvement of mitochondrial pathway in MCME-induced cell death. These findings indicate that MCME has cytotoxic effects on human cancer cells and exhibits promising anti-cancer activity by triggering apoptosis through the regulation of caspases and mitochondria.

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Synthetic sphingolipid analogs and anti-cancer drugs synergistically induced human colon and pancreatic cancer cell death through inhibiting ceramide metabolism

10.1101/2021.10.01.462804 ◽

2021 ◽

Author(s):

Jing Song ◽

Arie Dagan

Keyword(s):

Pancreatic Cancer ◽

Cell Death ◽

Cancer Cells ◽

Human Cancer ◽

Human Colon ◽

Cancer Drugs ◽

Human Cancer Cells ◽

Low Concentrations ◽

Anti Cancer ◽

Sphingolipid Analogs

AbstractCeramide metabolism is a potential target for anti-cancer therapy. Studies show that chemotherapeutic agents can induce apoptosis and it is mediated by ceramide. Synthesized sphingolipid analogs can induce cell death in human lymphocytes and leukemia cells. By screening a group of synthetic sphingolipid analogs, we found that low concentrations of AD2750 and AD2646 induced cell death in human cancer cells by preventing ceramide from converting to sphingomyelin, individually or in combination with commercial cancer drugs. The combination of low concentrations of Taxol and AD2750 or AD2646 significantly increased cell death on human colon cancer cells (HT29). Co-administering low concentrations of Doxorubicin with AD2750 or AD2646 elevated cellular toxicity on human pancreatic cancer cells (CRL1687). This synergistic effect is related to the elevated cellular ceramide. Combining AD2750 or AD2646 with chemotherapy drugs can be used to manipulate ceramide and sphingomyelin metabolism, potentially to affect the growth of human cancer cells and increase the effectiveness of anti-cancer drugs on killing cancer cells.

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CHOP Is Involved in Endoplasmic Reticulum Stress-induced Apoptosis by Enhancing DR5 Expression in Human Carcinoma Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m406933200 ◽

2004 ◽

Vol 279 (44) ◽

pp. 45495-45502 ◽

Cited By ~ 522

Author(s):

Hirohito Yamaguchi ◽

Hong-Gang Wang

Keyword(s):

Endoplasmic Reticulum ◽

Cell Death ◽

Er Stress ◽

Cancer Cells ◽

Human Cancer ◽

Carcinoma Cells ◽

Human Carcinoma ◽

Human Cancer Cells ◽

Induced Apoptosis ◽

Hct116 Cells

It has been shown that excess stress to the endoplasmic reticulum (ER) triggers apoptosis, but the mechanisms underlying these processes remain unclear. We and others have reported previously that DR5 expression is up-regulated in thapsigargin (THG)-treated human cancer cells. Here, we provide evidence that CHOP is involved in THG up-regulation of DR5, which is a critical step for ER stress-induced apoptosis in human cancer cells. In human colon cancer HCT116 cells, knockdown of DR5 by siRNA blocked THG-induced Bax conformational change along with caspase-3 activation and cell death. Moreover, inhibition of CHOP expression attenuated DR5 up-regulation and apoptosis induced by THG, whereas ectopic expression of DR5 restored the sensitivity of CHOP siRNA-transfected cells to THG-induced apoptosis. In addition to HCT116 cells, inhibition of CHOP or DR5 induction also attenuated THG-induced cell death in other cancer cell lines including LNCaP, A2780S, and DU145, indicating that CHOP and DR5 are critical for ER stress-mediated apoptosis in human carcinoma cells. Furthermore, we identified a potential CHOP-binding site in the 5′-flanking region of the DR5 gene. Mutation of this site abrogated the enhanced reporter activity in response to THG treatment. Together, our findings suggest that CHOP regulates ER stress-induced apoptosis, at least in part, through enhancing DR5 expression in some types of human cancer cells.

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Synthetic Sphingolipid Analogs and Anti-cancer Drugs Synergistically Induced Human Colon and Pancreatic Cancer Cell Death Through Inhibiting Ceramide Metabolism

10.21203/rs.3.rs-430456/v1 ◽

2021 ◽

Author(s):

Jing Song ◽

Arie Dagan

Keyword(s):

Pancreatic Cancer ◽

Cell Death ◽

Cancer Cells ◽

Human Cancer ◽

Human Colon ◽

Cancer Drugs ◽

Human Cancer Cells ◽

Low Concentrations ◽

Anti Cancer ◽

Sphingolipid Analogs

Abstract Ceramide metabolism is a potential target for anti-cancer therapy. Studies show that chemotherapeutic agents can induce apoptosis and it is mediated by ceramide. Synthesized sphingolipid analogs can induce cell death in human lymphocytes and leukemia cells. By screening a group of synthetic sphingolipid analogs, we found that low concentrations of AD2750 and AD2646 induced cell death in human cancer cells by preventing ceramide from converting to sphingomyelin, individually or in combination with commercial cancer drugs. The combination of low concentrations of Taxol and AD2750 or AD2646 significantly increased cell death on human colon cancer cells (HT29). Co-administering low concentrations of Doxorubicin with AD2750 or AD2646 elevated cellular toxicity on human pancreatic cancer cells (CRL1687). This synergistic effect is related to the elevated cellular ceramide. Combining AD2750 or AD2646 with chemotherapy drugs can be used to manipulate ceramide and sphingomyelin metabolism, potentially to affect the growth of human cancer cells and increase the effectiveness of anti-cancer drugs on killing cancer cells.

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The Modified Phenanthridine PJ34 Unveils an Exclusive Cell-Death Mechanism in Human Cancer Cells

Cancers ◽

10.3390/cancers12061628 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1628 ◽

Cited By ~ 2

Author(s):

Malka Cohen-Armon

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Cytotoxic Activity ◽

Cancer Cells ◽

Mitotic Spindle ◽

Human Cancer ◽

Parp Inhibitor ◽

Mitotic Catastrophe ◽

Proliferating Cells ◽

Human Cancer Cells

This overview summarizes recent data disclosing the efficacy of the PARP inhibitor PJ34 in exclusive eradication of a variety of human cancer cells without impairing healthy proliferating cells. Its cytotoxic activity in cancer cells is attributed to the insertion of specific un-repairable anomalies in the structure of their mitotic spindle, leading to mitotic catastrophe cell death. This mechanism paves the way to a new concept of cancer therapy.

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Suppression of FOXM1 Sensitizes Human Cancer Cells to Cell Death Induced by DNA-Damage

PLoS ONE ◽

10.1371/journal.pone.0031761 ◽

2012 ◽

Vol 7 (2) ◽

pp. e31761 ◽

Cited By ~ 47

Author(s):

Marianna Halasi ◽

Andrei L. Gartel

Keyword(s):

Dna Damage ◽

Cell Death ◽

Cancer Cells ◽

Human Cancer ◽

Human Cancer Cells

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Treatment of human cancer cells with selenite or tellurite in combination with auranofin enhances cell death due to redox shift

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2009.05.027 ◽

2009 ◽

Vol 47 (6) ◽

pp. 710-721 ◽

Cited By ~ 45

Author(s):

Maria Pia Rigobello ◽

Valentina Gandin ◽

Alessandra Folda ◽

Anna-Klara Rundlöf ◽

Aristi P. Fernandes ◽

...

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Human Cancer ◽

Human Cancer Cells

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

BioMed Research International ◽

10.1155/2020/4926821 ◽

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.

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