A Hydroalcoholic Extract from the Leaves of Nerium oleander Inhibits Glycolysis and Induces Selective Killing of Lung Cancer Cells

Calderón-Montaño, José Manuel; Burgos-Morón, Estefanía; Orta, Manuel Luís; Mateos, Santiago; López‐Lázaro, Miguel

doi:10.1055/s-0032-1328715

Cited by 43 publications

(32 citation statements)

References 42 publications

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“…Sreenivasan Y et al [4] revealed that oleandrin could selectively induce apoptosis of human malignant cells, but not normal primary cells such as peripheral blood mononuclear cells (PBMC) or neutrophils. In addition, Calderón-Montaño JM et al [28] also found that an extract from Nerium oleander selectively induced the death of lung cancer cells but not nonmalignant lung fibroblasts. An explanation of the potential mechanism of oleandrin-mediated apoptosis may be that normal cells lack an elevated expression of certain subunits of Na + , K + -ATPase (such as α3), which is typical of tumor cells and positively correlates with the sensitivity to oleandrin.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Intrinsic and Extrinsic Apoptotic Pathways in Osteosarcoma Cells Following Oleandrin Treatment

Zhu

Lei

et al. 2016

IJMS

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Our previous study has reported the anti-tumor effect of oleandrin on osteosarcoma (OS) cells. In the current study, we mainly explored its potential regulation on intrinsic and extrinsic apoptotic pathway in OS cells. Cells apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected using fluorescence staining and flow cytometry. Caspase-3 activity was detected using a commercial kit. The levels of cytoplasmic cytochrome c, mitochondrial cytochrome c, bcl-2, bax, caspase-9, Fas, FasL, caspase-8 and caspase-3 were detected by Western blotting. z-VAD-fmk was applied to block both intrinsic and extrinsic apoptosis pathways, and cells apoptosis was also tested. Furthermore, we used z-LEHD-fmk and Fas blocking antibody to inhibit intrinsic and extrinsic pathways, separately, and the selectivity of oleandrin on these pathways was explored. Results showed that oleandrin induced the apoptosis of OS cells, which was accompanied by an increase in ROS and a decrease in MMP. Furthermore, cytochrome c level was reduced in mitochondria but elevated in the cytoplasm. Caspase-3 activity was enhanced by oleandrin in a concentration- and time-dependent manner. Oleandrin also down-regulated the expression of bcl-2, but up-regulated bax, caspase-9, Fas, FasL, caspase-8 and caspase-3. In addition, the suppression of both apoptotic pathways by z-VAD-fmk greatly reverted the oleandrin-induced apoptosis. Moreover, the suppression of one pathway by a corresponding inhibitor did not affect the regulation of oleandrin on another pathway. Taken together, we concluded that oleandrin induced apoptosis of OS cells via activating both intrinsic and extrinsic apoptotic pathways.

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Section: Discussionmentioning

confidence: 99%

Regulation of Intrinsic and Extrinsic Apoptotic Pathways in Osteosarcoma Cells Following Oleandrin Treatment

Zhu

Lei

et al. 2016

IJMS

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“…The cardiac drugs digitoxin and digoxin, the semisynthetic cardiac glycoside UNBS1450, and two extracts from the plant Nerium oleander have entered clinical trials for the treatment of cancer (see http://clinicaltrials.gov/ and ref. [6, 7, 10, 20, 21]).…”

Section: Introductionmentioning

confidence: 99%

Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

Calderón-Montaño

Burgos-Morón

Orta

et al. 2014

BioMed Research International

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Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na+/K+-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typically inhibit cancer cell proliferation at nanomolar concentrations, and recent high-throughput screenings of drug libraries have therefore identified cardiac glycosides as potent inhibitors of cancer cell growth. Cardiac glycosides can also block tumor growth in rodent models, which further supports the idea that they have potential for cancer therapy. Evidence also suggests, however, that cardiac glycosides may not inhibit cancer cell proliferation selectively and the potent inhibition of tumor growth induced by cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact caused by their ability to selectively kill human cells versus rodent cells. This paper reviews such evidence and discusses experimental approaches that could be used to reveal the cancer therapeutic potential of cardiac glycosides in preclinical studies.

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“…We have observed recently that rodent cells are over 100 times more resistant than human cells to the cytotoxicity of an extract from the leaves of Nerium oleander [3]. The selectivity of our cardiac glycoside-containing extract towards human cancer cells was much lower or nonexistent when compared to human healthy cells.…”

mentioning

confidence: 72%

“…The selectivity of our cardiac glycoside-containing extract towards human cancer cells was much lower or nonexistent when compared to human healthy cells. Its selectivity was 10-fold when tested in human lung cancer cells (A549) versus human lung nonmalignant cells (MRC5), but it was very low or lacking when tested in human melanoma cells (UACC62) and colorectal cancer cells (HT29) versus the nonmalignant cells [3].…”

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confidence: 99%

Does the Nerium oleander extract PBI-05204 have potential for pancreatic cancer therapy?

et al. 2015

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A Hydroalcoholic Extract from the Leaves of Nerium oleander Inhibits Glycolysis and Induces Selective Killing of Lung Cancer Cells

Cited by 43 publications

References 42 publications

Regulation of Intrinsic and Extrinsic Apoptotic Pathways in Osteosarcoma Cells Following Oleandrin Treatment

Regulation of Intrinsic and Extrinsic Apoptotic Pathways in Osteosarcoma Cells Following Oleandrin Treatment

Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

Does the Nerium oleander extract PBI-05204 have potential for pancreatic cancer therapy?

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