Marine natural product lepadin A as a novel inducer of immunogenic cell death via CD91-dependent pathway

doi:10.1007/s13659-023-00401-3

Natural Products and Bioprospecting ›› 2023, Vol. 13 ›› Issue (5): 34-34.DOI: 10.1007/s13659-023-00401-3

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Marine natural product lepadin A as a novel inducer of immunogenic cell death via CD91-dependent pathway

Dalila Carbone¹, Carmela Gallo¹, Genoveffa Nuzzo¹, Giusi Barra¹, Mario Dell'Isola¹, Mario Affuso², Olimpia Follero¹, Federica Albiani², Clementina Sansone³, Emiliano Manzo¹, Giuliana d'Ippolito¹, Angelo Fontana^1,2

1. Institute of Biomolecular Chemistry, Consiglio Nazionale Delle Ricerche, Via Campi Flegrei 34, Pozzuoli, 80078, Naples, Italy;
2. Department of Biology, University of Naples "Federico II", Via Cupa Nuova Cinthia 21, 80126, Naples, Italy;
3. Stazione Zoologica Anton Dohrn, Istituto Nazionale di Biologia, Ecologia e Biotecnologie Marine, University of Naples "Federico II", Villa Comunale, 80121, Naples, Italy

Received:2023-08-01 Online:2023-11-03 Published:2023-10-24
Contact: Carmela Gallo,E-mail:carmen.gallo@icb.cnr.it
Supported by:
This research was founded by the project “Antitumor Drugs and Vaccines from the Sea (ADViSE)” (B43D18000240007) and the FISR COVID Project (B53C22003560002) funded by POR Campania FESR 2014–2020.

Marine natural product lepadin A as a novel inducer of immunogenic cell death via CD91-dependent pathway

1. Institute of Biomolecular Chemistry, Consiglio Nazionale Delle Ricerche, Via Campi Flegrei 34, Pozzuoli, 80078, Naples, Italy;
2. Department of Biology, University of Naples "Federico II", Via Cupa Nuova Cinthia 21, 80126, Naples, Italy;
3. Stazione Zoologica Anton Dohrn, Istituto Nazionale di Biologia, Ecologia e Biotecnologie Marine, University of Naples "Federico II", Villa Comunale, 80121, Naples, Italy

通讯作者: Carmela Gallo,E-mail:carmen.gallo@icb.cnr.it
基金资助:
This research was founded by the project “Antitumor Drugs and Vaccines from the Sea (ADViSE)” (B43D18000240007) and the FISR COVID Project (B53C22003560002) funded by POR Campania FESR 2014–2020.

Abstract

Abstract: Immunogenic Cell Death (ICD) represents a mechanism of enhancing T cell-driven response against tumor cells. The process is enabled by release of damage-associated molecular patterns (DAMPs) and cytokines by dying cells. Based on molecular studies and clinical marker assessment, ICD can be a new target for cancer chemotherapy hitherto restricted to a few conventional anticancer drugs. In view of the development of small molecules in targeted cancer therapy, we reported the preliminary evidence on the role of the natural product lepadin A (1) as a novel ICD inducer. Here we describe the ICD mechanism of lepadin A (1) by proving the translocation of the protein calreticulin (CRT) to the plasma membrane of human A2058 melanoma cells. CRT exposure is an ICD marker in clinical studies and was associated with the activation of the intrinsic apoptotic pathway in A2058 cells with lepadin A (1). After the treatment, the tumour cells acquired the ability to activate dendritic cells (DCs) with cytokine release and costimulatory molecule expression that is consistent with a phenotypic profile committed to priming T lymphocytes via a CD91-dependent mechanism. The effect of lepadin A (1) was dose-dependent and comparable to the response of the chemotherapy drug doxorubicin (2), a well-established ICD inducer.

Key words: Immunogenic cell death, Natural products, Anticancer, Immunotherapy, Drug discovery

摘要： Immunogenic Cell Death (ICD) represents a mechanism of enhancing T cell-driven response against tumor cells. The process is enabled by release of damage-associated molecular patterns (DAMPs) and cytokines by dying cells. Based on molecular studies and clinical marker assessment, ICD can be a new target for cancer chemotherapy hitherto restricted to a few conventional anticancer drugs. In view of the development of small molecules in targeted cancer therapy, we reported the preliminary evidence on the role of the natural product lepadin A (1) as a novel ICD inducer. Here we describe the ICD mechanism of lepadin A (1) by proving the translocation of the protein calreticulin (CRT) to the plasma membrane of human A2058 melanoma cells. CRT exposure is an ICD marker in clinical studies and was associated with the activation of the intrinsic apoptotic pathway in A2058 cells with lepadin A (1). After the treatment, the tumour cells acquired the ability to activate dendritic cells (DCs) with cytokine release and costimulatory molecule expression that is consistent with a phenotypic profile committed to priming T lymphocytes via a CD91-dependent mechanism. The effect of lepadin A (1) was dose-dependent and comparable to the response of the chemotherapy drug doxorubicin (2), a well-established ICD inducer.

关键词: Immunogenic cell death, Natural products, Anticancer, Immunotherapy, Drug discovery

Dalila Carbone, Carmela Gallo, Genoveffa Nuzzo, Giusi Barra, Mario Dell'Isola, Mario Affuso, Olimpia Follero, Federica Albiani, Clementina Sansone, Emiliano Manzo, Giuliana d'Ippolito, Angelo Fontana. Marine natural product lepadin A as a novel inducer of immunogenic cell death via CD91-dependent pathway[J]. Natural Products and Bioprospecting, 2023, 13(5): 34-34.

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Marine natural product lepadin A as a novel inducer of immunogenic cell death via CD91-dependent pathway

Marine natural product lepadin A as a novel inducer of immunogenic cell death via CD91-dependent pathway

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