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

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

Risultato della ricerca: Article

127 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

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Leukemia
Apoptosis
Cell Line
Stilbenes
Fas Ligand Protein
Caspase Inhibitors
Caspase 9
Mitochondrial Membrane Potential
Hematologic Neoplasms
Caspases
Tumor Cell Line
pterostilbene
3'-hydroxypterostilbene
Lymphoma
Neoplasms
Stem Cells
Pharmaceutical Preparations
resveratrol
Imatinib Mesylate
3,3',4,5'-tetrahydroxystilbene

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

Cita questo

Pterostilbene and 3'-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells. / Gebbia, Nicolo'; Grimaudo, Stefania; Meli, Maria; Abbadessa, Vincenzo; Dusonchet, Luisa; Gebbia, Nicola; Grisolia, Giuseppina; Pizzirani, Daniela; Crosta, Lucia; Simoni, Daniele; Roberti, Marinella; Barucchello, Riccardo; Di Cristina, Antonietta; Invidiata, Francesco; Crosta, Lucia.

In: THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, Vol. 37, 2005, pag. 1709-1726.

Risultato della ricerca: Article

Gebbia, N, Grimaudo, S, Meli, M, Abbadessa, V, Dusonchet, L, Gebbia, N, Grisolia, G, Pizzirani, D, Crosta, L, Simoni, D, Roberti, M, Barucchello, R, Di Cristina, A, Invidiata, F & Crosta, L 2005, 'Pterostilbene and 3'-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells', THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, vol. 37, pagg. 1709-1726.
Gebbia, Nicolo' ; Grimaudo, Stefania ; Meli, Maria ; Abbadessa, Vincenzo ; Dusonchet, Luisa ; Gebbia, Nicola ; Grisolia, Giuseppina ; Pizzirani, Daniela ; Crosta, Lucia ; Simoni, Daniele ; Roberti, Marinella ; Barucchello, Riccardo ; Di Cristina, Antonietta ; Invidiata, Francesco ; Crosta, Lucia. / Pterostilbene and 3'-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells. In: THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY. 2005 ; Vol. 37. pagg. 1709-1726.
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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.",
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T1 - Pterostilbene and 3'-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells

AU - Gebbia, Nicolo'

AU - Grimaudo, Stefania

AU - Meli, Maria

AU - Abbadessa, Vincenzo

AU - Dusonchet, Luisa

AU - Gebbia, Nicola

AU - Grisolia, Giuseppina

AU - Pizzirani, Daniela

AU - Crosta, Lucia

AU - Simoni, Daniele

AU - Roberti, Marinella

AU - Barucchello, Riccardo

AU - Di Cristina, Antonietta

AU - Invidiata, Francesco

AU - Crosta, Lucia

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - BCR-ABL

KW - apoptosis

KW - leukemia

KW - multidrug resistance

KW - stilbenes

UR - http://hdl.handle.net/10447/29526

M3 - Article

VL - 37

SP - 1709

EP - 1726

JO - THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

JF - THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

SN - 1357-2725

ER -