A [Pt(cis-1,3-diaminocycloalkane)Cl-2] analog exhibits hallmarks typical of immunogenic cell death inducers in model cancer cells

0551528 - BFÚ 2023 RIV US eng J - Článek v odborném periodiku
Novohradský, Vojtěch - Marková, Lenka - Kostrhunová, Hana - Kašpárková, Jana - Hoeschele, J. D. - Brabec, Viktor
A [Pt(cis-1,3-diaminocycloalkane)Cl-2] analog exhibits hallmarks typical of immunogenic cell death inducers in model cancer cells.
Journal of Inorganic Biochemistry. Roč. 226, JAN 2022 (2022), č. článku 111628. ISSN 0162-0134. E-ISSN 1873-3344
Grant CEP: GA MŠMT(CZ) LTAUSA18009; GA ČR(CZ) GA21-27514S
Institucionální podpora: RVO:68081707
Klíčová slova: anticancer therapy * autophagy * damps * calreticulin * mechanisms * induction
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 3.9, rok: 2022
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S0162013421002750?via%3Dihub

The platinum drugs belong to prevailing chemotherapeutics used in the treatment of cancer. At present, however, the search for new anticancer metal-based drugs that operate by the mechanisms distinct from those of the conventional chemotherapeutics is very active. Furthermore, it has been demonstrated that cytotoxic chemotherapy and immunotherapy may exert a highly synergistic anticancer activity. Thus, the development of antitumor platinum and other metal-based drugs that exhibit cytostatic effects and concurrently elicit immunogenic cell death (ICD) has shown promise for cancer treatment. Notably, conventional platinum drug oxaliplatin ([Pt (1R,2R-DACH)(oxalate)], DACH = diaminocyclohexane) is a well-known agent that displays both cytostatic and immune responses. Moreover, it was also demonstrated that even minor derivatization of the unleaving cycloalkyl moiety in oxaliplatin might have a pronounced effect on its immunomodulatory activity. Here, we investigated how replacing the 1R,2R- diaminocyclohexane ring by 1,3-diaminocycloalkane (alkane = butane, pentane, or hexane) affects the ability to evoke secretion of damage-associated molecular patterns characteristic of ICD in model murine colorectal carcinoma cell line CT26. The results indicate that among the investigated [Pt (cis-1,3-diaminocycloalkane)Cl2] complexes, the complex containing the cyclobutyl moiety exhibits the hallmarks typical of ICD inducers. Thus, [Pt(cis-1,3-diaminocyclobutane)Cl2] may expand the spectrum of anticancer chemotherapeutics capable of inducing ICD in cancer cells and might be of interest for further (pre)clinical development.
Trvalý link: https://hdl.handle.net/11104/0336893