Melanoma: Morphological essays of energetic tumor death under the influence of live mitochondria.

Abstract

e21561 Background: Global trials form a new mitochondrial paradigm for suppressing the growth of malignant tumors. The unique role of mitochondria (MC) in the processes of metabolism, proliferation, and cell death was proven by the establishment of signaling pathways and critical conditions for the self-organization and degradation of MC. There are still many unsolved problems in the development of a new strategy, including the absence of an integral picture of morphological changes in the tumor under the influence of mitochondrial therapy (MCT), and this determined the purpose of the study. Methods: The study included male and female Balb/c Nude mice weighing 21-22 g. B16/F10 melanoma was transplanted to mice subcutaneously, and suspension of live liver MC was injected intraperitoneally. MC were isolated by differential centrifugation (Avanti J-E high-speed centrifuge, BECKMAN COULTER, USA). After an MCT cycle, the melanoma structure was examined with hematoxylin and eosin staining and light microscopy (LEICA DM LS2). Results: Control samples of melanoma (without MCT) showed abundant vascularization with dense growth of epithelial-like cells with branched cytoplasm, an eccentric nucleus and a moderate content of melanin pigment. Massive hypoxic death, autolysis and autoxidation of tumor cells were registered in male mice after MCT, as well as matrix hyalinosis, pronounced subcutaneous tissue edema with segregation and necrotization of fat accumulations. The formation of a large cavity filled with detritus indicated signs of total tumor necrosis and ischemia. The accumulation of hyperchromic granules indicated the activation of granulocytic and phagocytic elements in the mechanism of tumor regression. Female mice showed rare small areas of necrosis, as well as pronounced fragmentation of nuclei and cytoplasm of cells in most fields of view induced by bioenergetic hypoxia, with the formation of apoptotic bodies. Along the edge of the cells subjected to autophagocytosis, melanin accumulated as it left the cells and accumulated as large granules, while small ones filled the space of the vessels. The process of melanoma regression was confirmed by a significant increase in free fibrous areas, where only faint cell shadows remained. Conclusions: The initial state of melanoma degrades under the influence of MCT inducing bioenergetic hypoxia in male and female Balb/c Nude mice in different ways. Gender, in fact, hormonal differences determine the dominance of different ways of cell death, necrosis (in males) and apoptosis (in females), while maintaining the MCT access to the processes of preventing tumor growth.