Pterostilbene and 3'-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells

Luisa Dusonchet, Nicolo' Gebbia, Vincenzo Abbadessa, Stefania Grimaudo, Maria Meli, Nicola Gebbia, Giuseppina Grisolia, Daniela Pizzirani, Lucia Crosta, Daniele Simoni, Marinella Roberti, Riccardo Barucchello, Antonietta Di Cristina, Francesco Invidiata, Lucia Crosta

Risultato della ricerca: Articlepeer review

136 Citazioni (Scopus)

Abstract

Pterostilbene and 3,5-hydroxypterostilbene are the natural 3,5-dimethoxy analogs of traps-resveratrol and piceatannol, two compounds which can induce apoptosis in tumor cells. In previous studies we demonstrated the importance of a 3,5-dimethoxy motif in conferring pro-apoptotic activity to stilbene based compounds so we now wanted to evaluate the ability of pterostilbene and 3,5-hydroxypterostilbene in inducing apoptosis in sensitive and resistant leukemia cells. When tested in sensitive cell lines, HL60 and HUT78, 3'-hydroxypterostilbene was 50-97 times more potent than traps-resveratrol in inducing apoptosis, while pterostilbene appeared barely active. However, both compounds, but not traps-resveratrol and piceatannol, were able to induce apoptosis in the two Fas-ligand resistant lymphoma cell lines, HUT78B1 and HUT78B3, and the multi drug-resistant leukemia cell lines HL60-R and K562-ADR (a Bcr-Abl-expressing cell line resistant to imatinib mesylate). Of note, pterostilbene-induced apoptosis was not inhibited by the pancaspase-inhibitor Z-VAD-fmk, suggesting that this compound acts through a caspase-independent pathway. On the contrary, 3'-hydroxypterostilbene seemed to trigger apoptosis through the intrinsic apoptotic pathway: indeed, it caused a marked disruption of the mitochondrial membrane potential A P and its apoptotic effects were inhibited by Z-VAD-fmk and the caspase-9-inhibitor Z-LEND-fmk. Moreover, pterostilbene and 3'-hydroxypterostilbene, when used at concentrations that elicit significant apoptotic effects in tumor cell lines, did not show any cytotoxicity in normal hemopoietic stem cells. In conclusion, our data show that pterostilbene and particularly 3'-hydroxypterostilbene are interesting antitumor natural compounds that may be useful in the treatment of resistant hematological malignancies, including imatinib, non-responsive neoplasms.
Lingua originaleEnglish
pagine (da-a)1709-1726
Numero di pagine18
RivistaTHE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume37
Stato di pubblicazionePublished - 2005

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

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