Cytotoxic and cytostatic effects of digitoxigenin monodigitoxoside (DGX) in human lung cancer cells and its link to Na,K-ATPase

Schneider, Naira Fernanda Zanchett; Persich, Lara; Rocha, Sayonarah C.; Ramos, Ana Luísa; Cortes, Vanessa Faria; Silva, Izabella Thaís; Munkert, Jennifer; Pádua, Rodrigo Maia de; Kreis, Wolfgang; Taranto, Alex Gutterres; Barbosa, Leandro A.; Braga, Fernão Castro; Simões, Cláudia Maria Oliveira

doi:10.1016/j.biopha.2017.10.128

Cited by 23 publications

(10 citation statements)

References 40 publications

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“…The cytotoxicity of seeds extract might be attributed to the occurrence of the high content of cardiac glycosides present in A. obesum (Versiani et al, 2014, Ahmed et al, 2017). As anticancer agents, cardiac glycosides triggered different cell death mechanisms including the intrinsic or the extrinsic pathway of apoptosis (Schneider et al, 2018, Juncker et al, 2011). Furthermore, cardiac glycosides induced autophagic cell death was described in breast, ovarian, colorectal, and lung cancer cells (Farah et al, 2016, Hsu et al, 2016, Kang et al, 2016, Wang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Cytogenotoxic effects of Adenium obesum seeds extracts on breast cancer cells

Ali

Farah

Abou-Tarboush

et al. 2019

Saudi Journal of Biological Sciences

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The extracts prepared from various areal parts of the Adenium obesum (Forssk.) Roem. & Schult. (Family: Apocynaceae) including leaves, fruit and seeds ethanolic extracts and seed aqueous extract were evaluated against MCF-7 cells in order to investigate its potential of cytogenotoxicity and induction of apoptosis. The ethanolic seeds extract had comparatively higher cytotoxicity (IC 50 ∼ 337 µg/ml). Further, apoptosis and DNA damaging potential of seeds ethanolic extract was analyzed by applying multiple sub-lethal concentrations and durations. Flow cytometry results revealed that maximum percentage of early apoptosis (37%) and late apoptosis (35%) were observed after 12 h exposure in concentrations 200 µg/ml and 300 µg/ml, respectively. Similarly, the higher effect of extract in terms of DNA damage by alkaline comet assay was registered after 12 h treatment at concentrations 200 and 300 µg/mL. The calculated total damage score (TDS) for these concentrations were 614 and 617, respectively. The above findings indicate that A. obesum ethanolic seeds extracts has cytogenotoxic properties that could be further explored for the potential source of chemotherapeutic lead against cancer.

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Section: Discussionmentioning

confidence: 99%

Cytogenotoxic effects of Adenium obesum seeds extracts on breast cancer cells

Ali

Farah

Abou-Tarboush

et al. 2019

Saudi Journal of Biological Sciences

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“…Isothiocyanates, including benzyl isothiocyanate and phenethyl isothiocyanate, reduced NSCLC metastasis by inducing oxidative stress, but also activated protective autophagy [ 50 , 51 ]. Digitoxigenin monodigitoxoside, a steroid glycoside from Digitalis lanata Ehrh., exerted long-term cytotoxicity via binding to Na/K-ATPase [ 52 ]. Gigantol from Dendrobium draconis Rchb.…”

Section: Discussionmentioning

confidence: 99%

Prodigiosin-Emerged PI3K/Beclin-1-Independent Pathway Elicits Autophagic Cell Death in Doxorubicin-Sensitive and -Resistant Lung Cancer

Chiu

Lin

Chen

et al. 2018

JCM

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Prodigiosin (PG) belongs to a family of prodiginines isolated from gram-negative bacteria. It is a water insoluble red pigment and a potent proapoptotic compound. This study elucidates the anti-tumor activity and underlying mechanism of PG in doxorubicin-sensitive (Dox-S) and doxorubicin-resistant (Dox-R) lung cancer cells. The cytotoxicity and cell death characteristics of PG in two cells were measured by MTT assay, cell cycle analysis, and apoptosis/autophagic marker analysis. Then, the potential mechanism of PG-induced cell death was evaluated through the phosphatidylinositol-4,5-bisphosphate 3-kinase-p85/Protein kinase B /mammalian target of rapamycin (PI3K-p85/Akt/mTOR) and Beclin-1/phosphatidylinositol-4,5-bisphosphate 3-kinase-Class III (Beclin-1/PI3K-Class III) signaling. Finally, in vivo efficacy was examined by intratracheal inoculation and treatment. There was similar cytotoxicity with PG in both Dox-S and Dox-R cells, where the half maximal inhibitory concentrations (IC50) were all in 10 μM. Based on a non-significant increase in the sub-G1 phase with an increase of microtubule-associated proteins 1A/1B light chain 3B-phosphatidylethanolamine conjugate (LC3-II), the cell death of both cells was categorized to achieve autophagy. Interestingly, an increase in cleaved-poly ADP ribose polymerase (cleaved-PARP) also showed the existence of an apoptosis-sensitive subpopulation. In both Dox-S and Dox-R cells, PI3K-p85/Akt/mTOR signaling pathways were reduced, which inhibited autophagy initiation. However, Beclin-1/PI3K-Class III downregulation implicated non-canonical autophagy pathways were involved in PG-induced autophagy. At completion of the PG regimen, tumors accumulated in the mice trachea and were attenuated by PG treatment, which indicated the efficacy of PG for both Dox-S and Dox-R lung cancer. All the above results concluded that PG is a potential chemotherapeutic agent for lung cancer regimens regardless of doxorubicin resistance.

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“…Hepatocellular carcinoma (HCC) is a primary liver cancer with high mortality and is the most common malignancy ( 1 ), which occurs frequently in Asia, Africa, southern Europe and China ( 2 ). Although early surgical resection and liver transplantation are effective treatments for HCC ( 3 ), the 5-year recurrence rate for HCC remains poor because of its high recurrence and metastasis rates ( 4 ). Therefore, useful prognostic and therapeutic indicators are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Integrative Transcriptomic, Proteomic and Functional Analysis Reveals ATP1B3 as a Diagnostic and Potential Therapeutic Target in Hepatocellular Carcinoma

Cai

et al. 2021

Front. Immunol.

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The Na+/K+-ATPase (NKA), has been proposed as a signal transducer involving various pathobiological processes, including tumorigenesis. However, the clinical relevance of NKA in hepatocellular carcinoma (HCC) has not been well studied. This study revealed the upregulation of mRNA of ATP1A1, ATP1B1, and ATP1B3 in HCC using TCGA, ICGC, and GEO database. Subsequently, ATP1B3 was demonstrated as an independent prognostic factor of overall survival (OS) of HCC. To investigate the potential mechanisms of ATP1B3 in HCC, we analyzed the co-expression network using LinkedOmics and found that ATP1B3 co-expressed genes were associated with immune-related biological processes. Furthermore, we found that ATP1B3 was correlated immune cell infiltration and immune-related cytokines expression in HCC. The protein level of ATP1B3 was also validated as a prognostic significance and was correlated with immune infiltration in HCC using two proteomics datasets. Finally, functional analysis revealed that ATP1B3 was increased in HCC cells and tissues, silenced ATP1B3 repressed HCC cell proliferation, migration, and promoted HCC cell apoptosis and epithelial to mesenchymal transition (EMT). In conclusion, these findings proved that ATP1B3 could be an oncogene and it was demonstrated as an independent prognostic factor and correlated with immune infiltration in HCC, revealing new insights into the prognostic role and potential immune regulation of ATP1B3 in HCC progression and provide a novel possible therapeutic strategy for HCC.

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Cytotoxic and cytostatic effects of digitoxigenin monodigitoxoside (DGX) in human lung cancer cells and its link to Na,K-ATPase

Cited by 23 publications

References 40 publications

Cytogenotoxic effects of Adenium obesum seeds extracts on breast cancer cells

Cytogenotoxic effects of Adenium obesum seeds extracts on breast cancer cells

Prodigiosin-Emerged PI3K/Beclin-1-Independent Pathway Elicits Autophagic Cell Death in Doxorubicin-Sensitive and -Resistant Lung Cancer

Integrative Transcriptomic, Proteomic and Functional Analysis Reveals ATP1B3 as a Diagnostic and Potential Therapeutic Target in Hepatocellular Carcinoma

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