The NF-κB inhibitor DHMEQ decreases survival factors, overcomes the protective activity of microenvironment and synergizes with chemotherapy agents in classical Hodgkin lymphoma.
The NF-κB inhibitor DHMEQ has shown preclinical activity in classical Hodgkin Lymphoma (cHL). Here we evaluated if DHMEQ could affect microenvironmental interactions and formation and improve the activity of drugs used in relapsed/refractory cHL. We demonstrated that DHMEQ down-regulated the NF-κB target genes IRF4 and CD40, the secretion of IL-6, CCL5, CCL17 and generated ROS. Cytotoxicity, CD30 down-modulation and CD30 shedding by DHMEQ were prevented by ROS scavenger NAC. DHMEQ overcame stimuli from CD40 engagement and fibroblasts and enhanced doxorubicin, cisplatin and gemcitabine activity. Our results suggest that DHMEQ may be a promising agent for future therapeutic strategies in cHL.
Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, PN, Italy.
Marta
M
Celegato
Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, PN, Italy.
Cinzia
C
Borghese
Department of Molecular Target Medicine, Aichi Medical University, Nagakute 480-1195, Japan.
Kazuo
K
Umezawa
Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, PN, Italy.
Naike
N
Casagrande
Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, PN, Italy; MATI (Microgravity Ageing Training Immobility) Excellence Center and Department of Medical and Biological Science, University of Udine, Udine, Italy.
Alfonso
A
Colombatti
Department of Pathology, CRO Aviano National Cancer Institute, Aviano, PN, Italy.
Antonino
A
Carbone
Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, PN, Italy. Electronic address: daldinucci@cro.it.
Donatella
D
Aldinucci
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D019013:CD40 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D054414:Chemokine CCL17 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D003512:Cyclohexanones / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D017730:Ki-1 Antigen / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects*; D000099218:Interferon Regulatory Factor-4
D000970:Antineoplastic Agents; D001549:Benzamides; D019013:CD40 Antigens; D054414:Chemokine CCL17; D018946:Chemokine CCL5; D003512:Cyclohexanones; D050835:Interferon Regulatory Factors; D015850:Interleukin-6; D017730:Ki-1 Antigen; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D000099218:Interferon Regulatory Factor-4; C106230:CCL17 protein, human; C483024:CCL5 protein, human; C464444:dehydroxymethylepoxyquinomicin
CD30; Hodgkin lymphoma; NF-κB inhibitors; Reactive oxygen species; Tumor microenvironment