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Periplocin, the most anti-proliferative constituent of Periploca sepium, specifically kills liposarcoma cells by death receptor mediated apoptosis.
Phytomedicine 2018; 51:162-170P

Abstract

BACKGROUND

During a screening of Chinese plants traditionally used for the treatment of cancer and related diseases, extracts of the root bark of Periploca sepium Bunge showed strong cytotoxic activity.

PURPOSE

Isolate and identify cytotoxic compounds from P. sepium and investigate the effects and mechanism of action on different cancer cell lines.

METHODS

Extracts obtained with solvents of different polarities of the root bark of P. sepium were tested for their anti-proliferative effects. The most active extract was subjected to activity-guided fractionation using different chromatographic methods. The most active compound was further investigated on sarcoma cell lines regarding its effects concerning apoptosis, DNA damage and death receptor expression.

RESULTS

We isolated the cardiac glycosides periplocin, glucosyl divostroside, periplogenin, periplocymarin and periplocoside M with periplocin exhibiting the lowest IC50 value against leukemia and liposarcoma cells. Liposarcomas are rare tumors within the heterogeneous group of soft tissue sarcomas and respond poorly to conventional treatments. Periplocin led to growth inhibition and apoptosis induction by changing the expression of death receptors and inducing DNA double strand breaks in SW-872 cells.

CONCLUSION

Periplocin displays a promising mechanism of action in sarcoma cells because altering the death receptor expression is an interesting target in sarcoma treatment especially to overcome TRAIL resistance.

Authors+Show Affiliations

Department of Orthopedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036 Graz, Austria.Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4/1, 8010 Graz, Austria.Department of Orthopedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036 Graz, Austria.Department of Orthopedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036 Graz, Austria.Department of Orthopedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036 Graz, Austria.Department of Orthopedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036 Graz, Austria.Division of Biomedical Research, Medical University Graz, Roseggerweg 48, 8036 Graz, Austria.Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Schubertstr. 1, 8010 Graz, Austria.Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4/1, 8010 Graz, Austria. Electronic address: rudolf.bauer@uni-graz.at.Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4/1, 8010 Graz, Austria.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30466613

Citation

Lohberger, Birgit, et al. "Periplocin, the Most Anti-proliferative Constituent of Periploca Sepium, Specifically Kills Liposarcoma Cells By Death Receptor Mediated Apoptosis." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 51, 2018, pp. 162-170.
Lohberger B, Wagner S, Wohlmuther J, et al. Periplocin, the most anti-proliferative constituent of Periploca sepium, specifically kills liposarcoma cells by death receptor mediated apoptosis. Phytomedicine. 2018;51:162-170.
Lohberger, B., Wagner, S., Wohlmuther, J., Kaltenegger, H., Stuendl, N., Leithner, A., ... Kretschmer, N. (2018). Periplocin, the most anti-proliferative constituent of Periploca sepium, specifically kills liposarcoma cells by death receptor mediated apoptosis. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 51, pp. 162-170. doi:10.1016/j.phymed.2018.10.008.
Lohberger B, et al. Periplocin, the Most Anti-proliferative Constituent of Periploca Sepium, Specifically Kills Liposarcoma Cells By Death Receptor Mediated Apoptosis. Phytomedicine. 2018 Dec 1;51:162-170. PubMed PMID: 30466613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Periplocin, the most anti-proliferative constituent of Periploca sepium, specifically kills liposarcoma cells by death receptor mediated apoptosis. AU - Lohberger,Birgit, AU - Wagner,Susanne, AU - Wohlmuther,Juliana, AU - Kaltenegger,Heike, AU - Stuendl,Nicole, AU - Leithner,Andreas, AU - Rinner,Beate, AU - Kunert,Olaf, AU - Bauer,Rudolf, AU - Kretschmer,Nadine, Y1 - 2018/10/11/ PY - 2018/06/15/received PY - 2018/10/05/revised PY - 2018/10/09/accepted PY - 2018/11/24/entrez PY - 2018/11/24/pubmed PY - 2019/2/5/medline KW - Apoptosis KW - Death receptors KW - Liposarcoma KW - Periploca sepium KW - Periplocin SP - 162 EP - 170 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 51 N2 - BACKGROUND: During a screening of Chinese plants traditionally used for the treatment of cancer and related diseases, extracts of the root bark of Periploca sepium Bunge showed strong cytotoxic activity. PURPOSE: Isolate and identify cytotoxic compounds from P. sepium and investigate the effects and mechanism of action on different cancer cell lines. METHODS: Extracts obtained with solvents of different polarities of the root bark of P. sepium were tested for their anti-proliferative effects. The most active extract was subjected to activity-guided fractionation using different chromatographic methods. The most active compound was further investigated on sarcoma cell lines regarding its effects concerning apoptosis, DNA damage and death receptor expression. RESULTS: We isolated the cardiac glycosides periplocin, glucosyl divostroside, periplogenin, periplocymarin and periplocoside M with periplocin exhibiting the lowest IC50 value against leukemia and liposarcoma cells. Liposarcomas are rare tumors within the heterogeneous group of soft tissue sarcomas and respond poorly to conventional treatments. Periplocin led to growth inhibition and apoptosis induction by changing the expression of death receptors and inducing DNA double strand breaks in SW-872 cells. CONCLUSION: Periplocin displays a promising mechanism of action in sarcoma cells because altering the death receptor expression is an interesting target in sarcoma treatment especially to overcome TRAIL resistance. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/30466613/Periplocin,_the_most_anti-proliferative_constituent_of_Periploca_sepium,_specifically_kills_liposarcoma_cells_by_death_receptor_mediated_apoptosis L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(18)30530-0 DB - PRIME DP - Unbound Medicine ER -