Quaternary Benzophenanthridine Alkaloids Act as Smac Mimetics
and Overcome Resistance to Apoptosis

J 2023

Quaternary Benzophenanthridine Alkaloids Act as Smac Mimetics and Overcome Resistance to Apoptosis

KULÍŠKOVÁ, Petra, Lucie VAŠÁTKOVÁ and Iva SLANINOVÁ

Basic information

Original name

Quaternary Benzophenanthridine Alkaloids Act as Smac Mimetics and Overcome Resistance to Apoptosis

Authors

KULÍŠKOVÁ, Petra (203 Czech Republic, belonging to the institution), Lucie VAŠÁTKOVÁ (203 Czech Republic, belonging to the institution) and Iva SLANINOVÁ (203 Czech Republic, belonging to the institution)

Edition

International Journal of Molecular Sciences, BASEL, MDPI, 2023, 1661-6596

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.600 in 2022

RIV identification code

RIV/00216224:14110/23:00132433

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/ijms242015405

UT WoS

001090041300001

Keywords in English

apoptosis; benzophenanthridine alkaloids; cancer; cell death; cIAP; Smac mimetic drug resistance; chelerythrine; sanguinarine

Abstract

V originále

Defects in cell death signaling pathways are one of the hallmarks of cancer and can lead to resistance to conventional therapy. Natural products are promising compounds that can overcome this resistance. In the present study we studied the effect of six quaternary benzophenanthridine alkaloids (QBAs), sanguinarine, chelerythrine, sanguirubine, chelirubine, sanguilutine, and chelilutine, on Jurkat leukemia cells, WT, and cell death deficient lines derived from them, CASP3/7/6(-/-) and FADD(-/-), and on solid tumor, human malignant melanoma, A375 cells. We demonstrated the ability of QBAs to overcome the resistance of these deficient cells and identified a novel mechanism for their action. Sanguinarine and sanguirubine completely and chelerythrine, sanguilutine, and chelilutine partially overcame the resistance of CASP3/7/6(-/-) and FADD(-/-) cells. By detection of cPARP, a marker of apoptosis, and pMLKL, a marker of necroptosis, we proved the ability of QBAs to induce both these cell deaths (bimodal cell death) with apoptosis preceding necroptosis. We identified the new mechanism of the cell death induction by QBAs, the downregulation of the apoptosis inhibitors cIAP1 and cIAP2, i.e., an effect similar to that of Smac mimetics.

Links

MUNI/A/1098/2022, interní kód MU

Name: Nespecifická imunita u chorob imunitního systému

Investor: Masaryk University, Non-specific immunity in immune system diseases

MUNI/A/1393/2022, interní kód MU

Name: Biomedicínské vědy III

Investor: Masaryk University

Citovat

KULÍŠKOVÁ, Petra, Lucie VAŠÁTKOVÁ and Iva SLANINOVÁ. Quaternary Benzophenanthridine Alkaloids Act as Smac Mimetics and Overcome Resistance to Apoptosis. International Journal of Molecular Sciences. BASEL: MDPI, 2023, vol. 24, No 20, p. 1-16. ISSN 1661-6596. Available from: https://dx.doi.org/10.3390/ijms242015405.

@article{2346798,
   author = {Kulíšková, Petra and Vašátková, Lucie and Slaninová, Iva},
   article_location = {BASEL},
   article_number = {20},
   doi = {http://dx.doi.org/10.3390/ijms242015405},
   keywords = {apoptosis; benzophenanthridine alkaloids; cancer; cell death; cIAP; Smac mimetic drug resistance; chelerythrine; sanguinarine},
   language = {eng},
   issn = {1661-6596},
   journal = {International Journal of Molecular Sciences},
   title = {Quaternary Benzophenanthridine Alkaloids Act as Smac Mimetics and Overcome Resistance to Apoptosis},
   url = {https://www.mdpi.com/1422-0067/24/20/15405},
   volume = {24},
   year = {2023}
}

TY  - JOUR
ID  - 2346798
AU  - Kulíšková, Petra - Vašátková, Lucie - Slaninová, Iva
PY  - 2023
TI  - Quaternary Benzophenanthridine Alkaloids Act as Smac Mimetics and Overcome Resistance to Apoptosis
JF  - International Journal of Molecular Sciences
VL  - 24
IS  - 20
SP  - 1-16
EP  - 1-16
PB  - MDPI
SN  - 16616596
KW  - apoptosis
KW  - benzophenanthridine alkaloids
KW  - cancer
KW  - cell death
KW  - cIAP
KW  - Smac mimetic drug resistance
KW  - chelerythrine
KW  - sanguinarine
UR  - https://www.mdpi.com/1422-0067/24/20/15405
N2  - Defects in cell death signaling pathways are one of the hallmarks of cancer and can lead to resistance to conventional therapy. Natural products are promising compounds that can overcome this resistance. In the present study we studied the effect of six quaternary benzophenanthridine alkaloids (QBAs), sanguinarine, chelerythrine, sanguirubine, chelirubine, sanguilutine, and chelilutine, on Jurkat leukemia cells, WT, and cell death deficient lines derived from them, CASP3/7/6(-/-) and FADD(-/-), and on solid tumor, human malignant melanoma, A375 cells. We demonstrated the ability of QBAs to overcome the resistance of these deficient cells and identified a novel mechanism for their action. Sanguinarine and sanguirubine completely and chelerythrine, sanguilutine, and chelilutine partially overcame the resistance of CASP3/7/6(-/-) and FADD(-/-) cells. By detection of cPARP, a marker of apoptosis, and pMLKL, a marker of necroptosis, we proved the ability of QBAs to induce both these cell deaths (bimodal cell death) with apoptosis preceding necroptosis. We identified the new mechanism of the cell death induction by QBAs, the downregulation of the apoptosis inhibitors cIAP1 and cIAP2, i.e., an effect similar to that of Smac mimetics.
ER  -

KULÍŠKOVÁ, Petra, Lucie VAŠÁTKOVÁ and Iva SLANINOVÁ. Quaternary Benzophenanthridine Alkaloids Act as Smac Mimetics and Overcome Resistance to Apoptosis. \textit{International Journal of Molecular Sciences}. BASEL: MDPI, 2023, vol.~24, No~20, p.~1-16. ISSN~1661-6596. Available from: https://dx.doi.org/10.3390/ijms242015405.

Detailed Information on Publication Record