Abstract
Cell autophagy and apoptosis processes are of interest in drug development and contribute to the chemotherapy outcomes of patients receiving cancer treatment. The functional roles of cyclic nucleotides in cells include maintenance of metabolic homeostasis. cGMP and steroid compounds participate in apoptotic and autophagic events, and modulate the function of multi-drug resistance proteins. Endogenous steroid and cyclic nucleotide ratios change with ageing and this may initiate detrimental changes in cell function. This study uses a computational chemistry approach to investigate molecular similarity within chemotherapeutic and steroid compound structures. Modulators of autophagy/apoptosis and endogenous steroid structures all demonstrate molecular similarity to the structure of cGMP. Relative molecular similarity within these structures facilitates additive and synergistic treatment effects. Endogenous steroids are natural modulators of autophagy and apoptosis; concentration changes consequently have the potential to impact cancer risks.
Highlights
The cell phenomena of autophagy and apoptosis are relevant to many medical conditions but best exploited in cancer chemotherapy
The data generated by this study reveal that phytochemical and synthetic drug structures with the same functional properties on cancer cells have the same cGMPfitting tendencies
Allicin fits to the same regions of the cGMP template as ML-9, acetylcarnitine and STF-62247; the latter is marketed as in vitro autophagy inducer
Summary
The cell phenomena of autophagy and apoptosis are relevant to many medical conditions but best exploited in cancer chemotherapy. Autophagy is regarded as a degradative recycling process primarily focused on cell survival and apoptosis. Structurally and functionally heterogeneous and promiscuous in regard to receptor targets, are classed as activators, inhibitors and dual-modulators [5]. Cellular homeostasis, maintained by a negative-feedback autophagic response triggered by ROS, may develop into a regulated death response when levels become overwhelming [6]. Calcium signaling is critical; ryanodine and inositol 1,4,5-triphosphate receptors (IP3R) modulate autophagic flux [7] [8]. Mitochondrial and cell apoptosis result from mitochondrial calcium overload [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
