Apoptotic activities of cardenolide glycosides from Asclepias subulata

Rascón-Valenzuela, Luisa Alondra; Velázquez, Carlos; Garibay‐Escobar, Adriana; Vilegas, Wagner; Medina-Juárez, Luis Ángel; Gámez-Meza, Nohemí; Robles‐Zepeda, Ramón Enrique

doi:10.1016/j.jep.2016.08.022

Cited by 13 publications

(11 citation statements)

References 29 publications

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“…In recent years, numerous cardenolides have shown apoptosis through caspase-dependent apoptosis including (+)-strebloside, 15 12,16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside, desglucouzarin, 25 periplocymarin, and periplocin. 26 Additionally, selected cardenolides have entered phase I and II clinical trials for the treatment of solid tumors with satisfactory safety and efficacy profiles.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Caspase-Dependent Apoptosis in Prostate Cancer Cells and Zebrafish by Corchorusoside C from Streptocaulon juventas

Anaya-Eugenio¹,

Addo²,

Ezzone³

et al. 2019

J. Nat. Prod.

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Corchorusoside C (1), isolated from Streptocaulon juventas collected in Vietnam, was found to be non-toxic in a zebrafish (Danio rerio) model and to induce cytotoxicity in several cancer cell lines with notable selective activity against prostate DU-145 cancer cells (IC 50 0.08 μM). Moreover, corchorusoside C induced DU-145 cell shrinkage and cell detachment. In CCD-112CoN colon normal cells, 1 showed significantly reduced cytotoxic activity (IC 50 2.3 μM). A preliminary mechanistic study indicated that 1 inhibits activity and protein expression of NF-κB (p50 and p65), IKK (α and β) and ICAM-1 in DU-145 cells. ROS concentrations increased at 5 h posttreatment and MTP decreased in a dose-dependent manner. Moreover, decreased protein expression of Bcl-2 and increased expression of PARP-1 was observed. Furthermore, corchorusoside C increased both the activity and protein levels of caspases 3 and 7. Additionally, 1 induced sub-G1 population increase of DU-145 cells and modulated caspases in zebrafish with non-differential morphological effects. Therefore, corchorusoside C (1) induces apoptosis in DU-145 cells and targets the same pathways both in vitro and in vivo in zebrafish. Thus, the use of zebrafish assays seems worthy of wider application than is currently employed for the evaluation of potential anticancer agents of natural origin.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Caspase-Dependent Apoptosis in Prostate Cancer Cells and Zebrafish by Corchorusoside C from Streptocaulon juventas

Anaya-Eugenio¹,

Addo²,

Ezzone³

et al. 2019

J. Nat. Prod.

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“…The extracts and secondary metabolites isolated from several parts of this plant have been reported to exhibit a range of pharmacological activities, including anti-inflammatory [ 10 ] and anticancer effects [ 4 , 6 ]. Compounds isolated from the milkweed plants (family: Apocynaceae or Asclepedaceae), such as 12,16-dihydroxycalotropin, calotropin, corotoxigenin 3-O-glycoside, desglucouzarin, uscharin, and 2′′-oxovoruscharin, have been explored as potential anticancer agents, owing to their ability to induce cell death through apoptosis and other pathways [ 11 – 13 ]. Recently, an ethanolic extract of the aerial parts of C .…”

Section: Introductionmentioning

confidence: 99%

Calotropis gigantea stem bark extract induced apoptosis related to ROS and ATP production in colon cancer cells

et al. 2021

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Conventional chemotherapeutic agents for colorectal cancer (CRC) cause systemic side effects and eventually become less efficacious owing to the development of drug resistance in cancer cells. Therefore, new therapeutic regimens have focused on the use of natural products. The anticancer activity of several parts of Calotropis gigantea has been reported; however, the effects of its stem bark extract on inhibition of cancer cell proliferation have not yet been examined. In this study, the anticancer activity of C. gigantea stem bark extract, both alone and in combination with 5-fluorouracil (5-FU), was evaluated. A crude ethanolic extract was prepared from dry, powdered C. gigantea barks using 95% ethanol. This was then partitioned to obtain dichloromethane (CGDCM), ethyl acetate, and water fractions. Quantitative analysis of the constituent secondary metabolites and calotropin was performed. These fractions exhibited cytotoxicity in HCT116 and HT-29 cells, with CGDCM showing the highest potency in both the cell lines. A combination of CGDCM and 5-FU significantly enhanced the cytotoxic effect. Moreover, the resistance of normal fibroblast, HFF-1, cells to this combination demonstrated its safety in normal cells. The combination significantly enhanced apoptosis through the mitochondria-dependent pathway. Additionally, the combination reduced adenosine triphosphate production and increased the production of reactive oxygen species, demonstrating the mechanisms involved in the induction of apoptosis. Our results suggest that CGDCM is a promising anti-cancer agent and may enhance apoptosis induction by 5-FU in the treatment of CRC, while minimizing toxicity toward healthy cells.

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“…According to Mo et al (2016) , calotropin activates the mitochondrial apoptotic pathway, accompanied by an increase in Bax/Bcl-2 ratio, decreased mitochondrial membrane potential, and increased reactive oxygen species (ROS) production and activation of caspases 3 and 9. Rascón-Valenzuela et al (2016) reported that calotropin and C3OG induce apoptosis by caspases 3, 8, and 9 activating the A549 cell line. Malayoside is a cardenolide with a similar structure to C3OG, which showed a cytotoxic and apoptotic effect on the NCI-H460 lung cell line.…”

Section: Discussionmentioning

confidence: 99%

“…They also showed selective cytotoxicity by not significantly affecting the non-cancerous human cell line and the murine cancer cell line ( Rascón-Valenzuela et al, 2015 ). Additionally, these cardenolides induced cell death through caspase-dependent apoptosis, activated by an extrinsic pathway ( Rascón-Valenzuela et al, 2016 ). Furthermore, recent studies have shown that calotropin inhibits the enzymatic activity of the Na + /K + -ATPase ( Pederson et al, 2020 ; Agrawal et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Calotropin and corotoxigenin 3-O-glucopyranoside from the desert milkweed Asclepias subulata inhibit the Na⁺/K⁺-ATPase activity

Meneses-Sagrero

Rascón-Valenzuela

García‐Ramos³

et al. 2022

PeerJ

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Na+/K+-ATPase is an essential transmembrane enzyme found in all mammalian cells with critical functions for cell ion homeostasis. The inhibition of this enzyme by several cardiotonic steroids (CTS) has been associated with the cytotoxic effect on cancer cell lines of phytochemicals such as ouabain and digitoxin. This study evaluated the inhibitory capacity of cardenolides calotropin and corotoxigenin 3-O-glucopyranoside (C3OG) from Asclepias subulata over the Na+/K+-ATPase activity in vitro and silico. The inhibitory assays showed that calotropin and C3OG decreased the Na+/K+-ATPase activity with IC50 values of 0.27 and 0.87 μM, respectively. Furthermore, the molecules presented an uncompetitive inhibition on Na+/K+-ATPase activity, with Ki values of 0.2 μM to calotropin and 0.5 μM to C3OG. Furthermore, the molecular modeling indicated that calotropin and C3OG might interact with the Thr797 and Gln111 residues, considered essential to the interaction with the Na+/K+-ATPase. Besides, these cardenolides can interact with amino acid residues such as Phe783, Leu125, and Ala323, to establish hydrophobic interactions on the binding site. Considering the results, these provide novel evidence about the mechanism of action of cardenolides from A. subulata, proposing that C3OG is a novel cardenolide that deserves further consideration for in vitro cellular antiproliferative assays and in vivo studies as an anticancer molecule.

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Apoptotic activities of cardenolide glycosides from Asclepias subulata

Abstract: In this study was found that cardenolide glycosides, 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, isolated from A. subulata induced the cell death trough caspase-dependent apoptosis, which was activated, preferably, by extrinsic pathway.

Cited by 13 publications

References 29 publications

Caspase-Dependent Apoptosis in Prostate Cancer Cells and Zebrafish by Corchorusoside C from Streptocaulon juventas

Caspase-Dependent Apoptosis in Prostate Cancer Cells and Zebrafish by Corchorusoside C from Streptocaulon juventas

Calotropis gigantea stem bark extract induced apoptosis related to ROS and ATP production in colon cancer cells

Calotropin and corotoxigenin 3-O-glucopyranoside from the desert milkweed Asclepias subulata inhibit the Na⁺/K⁺-ATPase activity

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Apoptotic activities of cardenolide glycosides from Asclepias subulata

Abstract: In this study was found that cardenolide glycosides, 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, isolated from A. subulata induced the cell death trough caspase-dependent apoptosis, which was activated, preferably, by extrinsic pathway.

Cited by 13 publications

References 29 publications

Caspase-Dependent Apoptosis in Prostate Cancer Cells and Zebrafish by Corchorusoside C from Streptocaulon juventas

Caspase-Dependent Apoptosis in Prostate Cancer Cells and Zebrafish by Corchorusoside C from Streptocaulon juventas

Calotropis gigantea stem bark extract induced apoptosis related to ROS and ATP production in colon cancer cells

Calotropin and corotoxigenin 3-O-glucopyranoside from the desert milkweed Asclepias subulata inhibit the Na+/K+-ATPase activity

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Calotropin and corotoxigenin 3-O-glucopyranoside from the desert milkweed Asclepias subulata inhibit the Na⁺/K⁺-ATPase activity