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Cell Death Discovery
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Humic substances enhance the anti-cancer efficacy of standard therapies
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  • Published: 31 March 2026

Humic substances enhance the anti-cancer efficacy of standard therapies

  • Paola Bianca1,2 na1,
  • Chiara Modica3 na1,
  • Mariavittoria Verrillo4 na1,
  • Melania Lo Iacono1 na1,
  • Laura Rosa Mangiapane1,
  • Kimiya Shams3,
  • Narges Roozafzay1,
  • Vincenzo Davide Pantina3,
  • Giulia Bozzari3,
  • Sebastiano Di Bella  ORCID: orcid.org/0000-0001-7161-303X3,
  • Francesco Orilio3,
  • Caterina D’Accardo3,
  • Gaetana Porcelli1,
  • Roberta Drago3,
  • Francesco Verona2,3,
  • Rosario Nicola Brancaccio3,
  • Alice Turdo  ORCID: orcid.org/0000-0002-6152-49031,
  • Miriam Gaggianesi3,
  • Simone Di Franco  ORCID: orcid.org/0000-0002-6217-21613,
  • Vincenza Cozzolino4,
  • Riccardo Spaccini4,
  • Matilde Todaro1,2 na2 &
  • …
  • Giorgio Stassi  ORCID: orcid.org/0000-0002-1016-90593,5 na2 

Cell Death Discovery , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cancer therapy
  • Natural products

Abstract

The green oncology paradigm emphasizes the use of natural products in cancer treatment to protect the environment while reducing the adverse effects associated with conventional therapies. In this context, humic substances (HSs), derived from the degradation of waste biomass, have emerged as promising candidates due to their diverse bioactive properties. Beyond their well-known antioxidant and antimicrobial effects, this study demonstrates the antitumor potential of HSs extracted from olive (HS-OL) and artichoke (HS-CYN). Our results reveal that HS-OL and HS-CYN significantly induce DNA damage by triggering apoptosis and reducing cell viability in cancer cells across various histotypes. When used in combination with standard therapies, these HSs enhance therapeutic efficacy, enabling the use of lower doses of chemotherapeutic agents while maintaining their effectiveness. The introduction of HSs into cancer treatment represents a sustainable and innovative approach that not only reduces the ecological footprint but also minimizes the side effects associated with traditional anticancer drugs, offering a dual benefit for both patients and the environment.

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Data availability

All relevant raw data will be available on request from the corresponding author.

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Acknowledgements

We thank Irene Pillitteri for technical assistance.

Funding

The research leading to these results has received funding by European Union, FESR FSE PON Ricerca e Innovazione 2014-2020 DM 1062/2021 to PB, MLI and CM; European Union, NextGenerationEU initiative under the Italian Ministry of University and Research as a part of the PNRR-M4C2-l1.3 Project PE00000019 “HEAL ITALIA” CUP B73C22001250006 to SDB, SDF, MT, and GS; Fondo Finalizzato di Ateneo (FFR)-2024 to MLI, CM, SDB, AT, and MG; AIRC under IG 2024-ID.30306 project to MT; Next Generation EU, PNRR-MCNT1-2023- 12377772—CUP:173C24000370007 to PB and FV; SIS-NET, “ID S4-01.P0001”—CUP: I83C22001810007 to RD; INNOVA—Hub Life Science Diagnostica Avanzata (HLS-DA), PNC-E3-2022-23683266 to CD; Italian Ministry of Health, project “GENESIS ATI, CUP B77G22000340005 to RNB; GP is recipient of the Pezcoller Foundation -SIC- Marina Larcher Fogazzaro fellowship; VDP is a recipient of Fellowship for Italy Post-Doc 2025. This work was supported by Fondazione Umberto Veronesi Fellowship 2023–2024 to MV.

Author information

Author notes

  1. These authors contributed equally: Paola Bianca, Chiara Modica, Mariavittoria Verrillo, Melania Lo Iacono.

  2. These authors jointly supervised this work: Matilde Todaro, Giorgio Stassi.

Authors and Affiliations

  1. Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy

    Paola Bianca, Melania Lo Iacono, Laura Rosa Mangiapane, Narges Roozafzay, Gaetana Porcelli, Alice Turdo & Matilde Todaro

  2. Azienda Ospedaliera Universitaria Policlinico “Paolo Giaccone” (AOUP), Palermo, Italy

    Paola Bianca, Francesco Verona & Matilde Todaro

  3. Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, Palermo, Italy

    Chiara Modica, Kimiya Shams, Vincenzo Davide Pantina, Giulia Bozzari, Sebastiano Di Bella, Francesco Orilio, Caterina D’Accardo, Roberta Drago, Francesco Verona, Rosario Nicola Brancaccio, Miriam Gaggianesi, Simone Di Franco & Giorgio Stassi

  4. Department of Agricultural Sciences, University of Naples Federico II, Naples, Italy

    Mariavittoria Verrillo, Vincenza Cozzolino & Riccardo Spaccini

  5. IRCCS SDN, Naples, Italy

    Giorgio Stassi

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  1. Paola Bianca
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  2. Chiara Modica
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  3. Mariavittoria Verrillo
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PB, MLI, MV, CM, MT, and GS conceived and designed the experiments; PB, MLI, MV, CM, KS, VDP, NR, LRM, CD, GP, RD, GB, and FV carried out the experiments; PB, MLI, MV, CM, VDP, LRM, CD, GP, RD, GB, and FV analyzed and elaborated data; AT, MG, SDF, VC, and RS supplied scientific suggestions and critical review; SDB, RNB and FO executed the bioinformatics analysis; PB, MLI, MV, CM, and GS wrote the manuscript. All authors revised the manuscript.

Corresponding author

Correspondence to Giorgio Stassi.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Patient samples were provided by the University Hospital “P. Giaccone” and the Hospital “Ospedali Riuniti Villa Sofia-Cervello”, in accordance with the ethical standards of the Institutional Committee responsible for human experimentation (authorization CE9/2015).

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Bianca, P., Modica, C., Verrillo, M. et al. Humic substances enhance the anti-cancer efficacy of standard therapies. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-03083-1

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  • Received: 30 June 2025

  • Revised: 12 February 2026

  • Accepted: 12 March 2026

  • Published: 31 March 2026

  • DOI: https://doi.org/10.1038/s41420-026-03083-1

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