Search for and identification of molecular targets of angucycline antibiotic landomycin E in human tumor cells

Abstract

Study of cellular and molecular mechanisms of anticancer activity of novel perspective angucycline antibiotic landomycin E was carried out. It was revealed that this compound uses mechanisms of apoptosis induction in tumor cells that differ from such mechanisms used by structurally related drug doxorubicin which is widely applied in clinics. In particular, landomycin E blocks cells in G1 phase of cell cycle, and this action is mediated by the reactive oxygen species. Such G1-specificity of landomycin E action of can be of great importance in chemotherapy, since it is known that cancer stem cells which are responsible for recurrent tumors, are staying mainly in G0/G1 phase, and, thus, are insensitive to most anticancer drugs. Application of Western-blot analysis for studying potential intracellular targets of the landomycin E action allowed identifying procaspase-7 as a targeted effector apoptotic protein. There are no other cases of direct activation of this enzyme by the anticancer drugs described in literature till now. Thus, such a unique mechanism of anticancer activity might allow landomycin E to kill tumor cells effectively even in the absence of other key enzymes involved in apoptosis, such as caspase-3. Taking into consideration high antineoplastic potential of landomycin E and unique mechanism of its action, this antibiotic could be recommended as anticancer drug of second line defense at treatment of cancer patients.

Keywords

• anticancer drugs
• tumor drug resistance
• landomycin e
• apoptosis
• cell cycle