S‐Adenosylmethionine‐mediated apoptosis is potentiated by autophagy inhibition induced by chloroquine in human breast cancer cells

Cave, Donatella Delle; Desiderio, Vincenzo; Mosca, Laura; Ilisso, Concetta Paola; Mele, Luigi; Caraglia, Michele; Cacciapuoti, Giovanna; Porcelli, Marina

doi:10.1002/jcp.26015

Cited by 35 publications

(48 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We evaluated the antiproliferative effects of AdoMet on two HNSC cell lines: oral cancer Cal-33 and laryngeal cancer JHU-SCC-011 cells, using concentrations of AdoMet ranging from 3 to 500 µM, for different treatment times. As reported in Figure 1 (Cave et al, 2018;Ilisso et al, 2015;Ilisso et al, 2016).…”

Section: Evaluation Of the Effects Of Adomet On Two Head And Neck Cmentioning

confidence: 69%

AdoMet triggers apoptosis in head and neck squamous cancer by inducing ER stress and potentiates cell sensitivity to cisplatin

Mosca

Pagano

Ilisso

et al. 2018

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

S‐Adenosyl‐l‐methionine (AdoMet) is a naturally and widely occurring sulfonium compound that plays a primary role in cell metabolism and acts as the principal methyl donor in many methylation reactions. AdoMet also exhibits antiproliferative and proapoptotic activities in different cancer cells. However, the molecular mechanisms underlying the effects exerted by AdoMet have only been partially studied. In the current study, we evaluated the antiproliferative effect of AdoMet on Cal‐33 oral and JHU‐SCC‐011 laryngeal squamous cancer cells to define the underlying mechanisms. We demonstrated that AdoMet induced apoptosis in Cal‐33 and JHU‐SCC‐011 cells, involving a caspase‐dependent mechanism paralleled by an increased Bax/Bcl‐2 ratio. Moreover, we showed, for the first time, that AdoMet induced ER‐stress in Cal‐33 cells and activated the unfolded protein response, which can be responsible for apoptosis induction through the activation of CHOP and JNK. In addition, AdoMet‐induced ER‐stress was followed by autophagy with a consistent increase in the levels of the autophagic marker LC3B‐II, which was indeed potentiated by the autophago‐lysosome inhibitor chloroquine. As both escape from apoptosis and decreased activation of JNK are mechanisms of resistance to cisplatin (cDPP), an agent usually used in cancer therapy, we have evaluated the effects of AdoMet in combination with cDPP on Cal‐33 cells. Our data showed that the combined treatment resulted in a strong synergism in inhibiting cell proliferation and in enhancing apoptosis via intrinsic mechanism. These results demonstrate that AdoMet has ER‐stress‐mediated antiproliferative activity and synergizes with cDDP on cell growth inhibition, thus providing the basis for its use in new anticancer strategies.

show abstract

Section: Evaluation Of the Effects Of Adomet On Two Head And Neck Cmentioning

confidence: 69%

AdoMet triggers apoptosis in head and neck squamous cancer by inducing ER stress and potentiates cell sensitivity to cisplatin

Mosca

Pagano

Ilisso

et al. 2018

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In recent years, it has been shown to possess antiproliferative properties in various cancer cells. It has also inhibited the proliferation of breast cancer cells MCF-7 by inducing both autophagy and apoptosis [3]. Luo et al [4] indicated that SAM treatment inhibited cell growth in gastric and colon cancer cells, and the inhibitory effect was significantly higher than that in normal cells.…”

Section: Introductionmentioning

confidence: 99%

Effect of S-Allyl –L-Cysteine on MCF-7 Cell Line 3-Mercaptopyruvate Sulfurtransferase/Sulfane Sulfur System, Viability and Apoptosis

Bronowicka-Adamska

Bentke

Lasota

et al. 2020

IJMS

View full text Add to dashboard Cite

The S-Allyl-L-cysteine (SAC) component of aged garlic extract (AGE) is proven to have anticancer, antihepatotoxic, neuroprotective and neurotrophic properties. γ-Cystathionase (CTH), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (MPST) are involved in H2S/sulfane sulfur endogenous formation from L-cysteine. The aim of the study was to determine the effect of SAC on MCF-7 cells survival and apoptosis, which is a widely known approach to reduce the number of cancer cells. An additional goal of this paper was to investigate the effect of SAC on the activity and expression of enzymes involved in H2S production. The experiments were carried out in the human breast adenocarcinoma cell line MCF-7. Changes in the cell viability were determined by MTT assay. Cell survival was determined by flow cytometry (FC). Changes in enzymes expression were analyzed using Western blot. After 24 h and 48 h incubation with 2245 µM SAC, induction of late apoptosis was observed. A decrease in cell viability was observed with increasing SAC concentration and incubation time. SAC had no significant cytotoxic effect on the MCF-7 cells upon all analyzed concentrations. CTH, MPST and CBS expression were confirmed in non-treated MCF-7 cells. Significant decrease in MPST activity at 2245 µM SAC after 24 h and 48 h incubation vs. 1000 µM SAC was associated with decrease in sulfane sulfur levels. The presented results show promising SAC effects regarding the deterioration of the MCF-7 cells’ condition in reducing their viability through the downregulation of MPST expression and sulfate sulfur level reduction.

show abstract

“…Despite emerging data from the literature on the anti-proliferative and anti-metastatic effects exerted by AdoMet in a variety of cancer cells are accumulating (8)(9)(10)(11)(12)(13), currently, only limited data are available on the molecular mechanisms underlying the anticancer effects of AdoMet on HNSCC (13), and the role of AdoMet in the invasion and migration of HNSCC has not been investigated to date, at least to the best of our knowledge.…”

Section: Discussionmentioning

confidence: 99%

“…compound exerts pleiotropic effects on signal transduction in a variety of cell types and that AdoMet is able to halt the progression of several human tumors (8)(9)(10)(11)(12)(13).…”

Section: Effects Of S-adenosyl-l-methionine On the Invasion And Migramentioning

confidence: 99%

Effects of S‑adenosyl‑L‑methionine on the invasion and migration of head and neck squamous cancer cells and analysis of the underlying mechanisms

et al. 2020

Self Cite

View full text Add to dashboard Cite

S-Adenosyl-L-methionine (AdoMet) is the principal methyl donor in transmethylation reactions fundamental to sustaining epigenetic modifications. Over the past decade, AdoMet has been extensively investigated for its antiproliferative, pro-apoptotic and anti-metastatic roles in several types of human cancer. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide, and is an aggressive type of cancer that is associated with a high recurrence rate, metastasis and poor treatment outcomes. The present study demonstrates, for the first time, to the best of our knowledge, that AdoMet induces cell cycle arrest and inhibits the migratory and invasive ability of two different HNSCC cell lines, oral Cal-33 and laryngeal JHU-SCC-011 cells. In both cell lines, AdoMet attenuated cell cycle progression, decreased the protein level of several cyclins and downregulated the expression of p21 cell cycle inhibitor. Moreover, AdoMet was able to inhibit Cal-33 and JHU-SCC-011 cell migration in a dose-dependent manner after 24 and 48 h, respectively, and also induced a significant reduction in the cell invasive ability, as demonstrated by Matrigel invasion assay monitored by the xCELLigence RTCA system. Western blot analysis of several migration and invasion markers confirmed the inhibitory effects exerted by AdoMet on these processes and highlighted AKT, β-catenin and small mothers against decapentaplegic (SMAD) as the main signaling pathways modulated by AdoMet. The present study also demonstrated that the combination of AdoMet and cisplatin synergistically inhibited HNSCC cell migration. Taken together, these findings demonstrate that the physiological compound, AdoMet, affects the motility and extracellular matrix invasive capability in HNSCC. Thus, AdoMet may prove to be a good candidate for future drug development against metastatic cancer.

show abstract

S‐Adenosylmethionine‐mediated apoptosis is potentiated by autophagy inhibition induced by chloroquine in human breast cancer cells

Cited by 35 publications

References 61 publications

AdoMet triggers apoptosis in head and neck squamous cancer by inducing ER stress and potentiates cell sensitivity to cisplatin

AdoMet triggers apoptosis in head and neck squamous cancer by inducing ER stress and potentiates cell sensitivity to cisplatin

Effect of S-Allyl –L-Cysteine on MCF-7 Cell Line 3-Mercaptopyruvate Sulfurtransferase/Sulfane Sulfur System, Viability and Apoptosis

Effects of S‑adenosyl‑L‑methionine on the invasion and migration of head and neck squamous cancer cells and analysis of the underlying mechanisms

Contact Info

Product

Resources

About