Novel methylsulfonyl chalcones as potential antiproliferative drugs for human prostate cancer: involvement of the intrinsic pathway of apoptosis
| Autor: | Frederique Martin, Christelle Pouget, Bassel Ismail, Rokhaya Gueye, David Yannick Leger, Youness Limami, Jean-Louis Beneytout, Lamia Ghezali, Mona Diab-Assaf, Bertrand Liagre, Catherine Fagnère, Jean-Luc Duroux |
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| Přispěvatelé: | Laboratoire de Chimie des Substances Naturelles (LCSN), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Lebanese University [Beirut] (LU) |
| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Antineoplastic Agents Apoptosis DNA Fragmentation Biology 03 medical and health sciences Prostate cancer 0302 clinical medicine Chalcones DU145 Cell Line Tumor medicine Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Sulfones Protein kinase B 030304 developmental biology Cell Proliferation 0303 health sciences Caspase 8 Oncogene [CHIM.ORGA]Chemical Sciences/Organic chemistry NF-kappa B Cancer Prostatic Neoplasms medicine.disease Caspase 9 3. Good health Cell biology Oncogene Protein v-akt Oncology Mechanism of action Cyclooxygenase 2 030220 oncology & carcinogenesis Cancer research Signal transduction medicine.symptom Poly(ADP-ribose) Polymerases Signal Transduction |
| Zdroj: | International Journal of Oncology International Journal of Oncology, Spandidos Publications, 2013, 43 (4), pp.1160-1168. ⟨10.3892/ijo.2013.2024⟩ |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2013.2024⟩ |
| Popis: | International audience; Limited success has been achieved in extending the survival of patients with metastatic and hormone-refractory prostate cancer (HRPC). There is a strong need for novel agents in the treatment and prevention of HRPC. In the present study, the apoptotic mechanism of action of RG003 (2'-hydroxy-4- methylsulfonylchalcone) and RG005 (4'-chloro-2'-hydroxy-4- methylsulfonylchalcone) in association with intracellular signalling pathways was investigated in the hormone-independent prostate carcinoma cells PC-3 and DU145. We showed that these compounds induced apoptosis through the intrinsic pathway but not through the extrinsic one. We showed that synthetic chalcones induced an activation of caspase-9 but not caspase-8 in PC-3 cells. Even if both chalcones induced apoptosis in PC-3 cells, a dominant effect of RG003 treatment was observed resulting in a disruption of δm, caspase-9 and caspase-3 activation, PARP cleavage and DNA fragmentation. Furthermore, in regard to our results, it is clear that the simultaneous inhibition of Akt and NF-κB signalling can significantly contribute to the anticancer effects of RG003 and RG005 in PC-3 prostate cancer cells. NF-κB inhibition was correlated with the reduction of COX-2 expression and induction of apoptosis. Our results clearly indicate for the first time that RG003 and RG005 exert their potent anti proliferative and pro-apoptotic effects through the modulation of Akt/NF-κB/COX-2 signal transduction pathways in PC-3 prostate cancer cells with a dominant effect for RG003 |
| Databáze: | OpenAIRE |
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