Cancer development is associated with the deregulation of various cell signaling pathways brought on by certain genetic and epigenetic alterations. Therefore, novel therapeutic strategies have been developed to target those pathways. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) (PI3K/Akt/mTOR) pathway is one major deregulated pathway in various types of cancer. Several anticancer drug candidates are currently being investigated in preclinical and/or clinical studies to target this pathway. Natural bioactive compounds provide an excellent source for anticancer drug development. Curcumin and plumbagin are two potential anticancer compounds that have been shown to target the PI3K/Akt/mTOR pathway individually. However, their combinatorial effect on cancer cells is still unknown. This study aims to investigate the synergistic effect of these two compounds on the PI3K/Akt/mTOR pathway by employing a sequential molecular docking and molecular dynamics (MD) analysis. An increase in binding affinity and a decrease in inhibition constant have been observed when curcumin and plumbagin were subjected to sequential docking against the key proteins PI3K, Akt, and mTOR. The MD simulations and molecular mechanics combined with generalized Born surface area (MM-GBSA) analyses validated the target proteins’ more stable conformation when interacting with the curcumin and plumbagin combination. This indicates the synergistic role of curcumin and plumbagin against cancer cells and the possible dose advantage when used in combination. The findings of this study pave the way for further investigation of their combinatorial effect on cancer cells in vitro and in vivo models.
Cancer and diabetes mellitus (DM) are among the leading causes of mortality and morbidity in the global arena. Lately, several studies demonstrated that DM could promote cancer. However, the exact mechanism(s) highlighting this association are largely untouched and require comprehensive detailing. In the present review, we aimed to explore and decipher the possible mechanism of DM an cancer association. Hyperglycemia could be a subordinate plausible explanation of carcinogenesis in the diabatic patient. It is well known that high glucose levels may help in cancer proliferation. In addition, chronic inflammation, the other well‐known factor of diabetes, could also play a role in carcinogenesis. Moreover, the numerous medicines to treat diabetes either increase or reduce cancer risk. Insulin is one of the potent growth factors that promotes cell propagation and induces cancer directly or via insulin like growth factor‐1. On the other hand, hyperinsulinemia leads to an increased activity of growth factor‐1 by inhibiting growth factor binding protein‐1. To improve cancer prognosis, individuals with diabetes should be screened to discover cancer at an early stage and treated appropriately.
The recent advancement of nanoparticles (NPs) holds significant potential for treating various ailments. NPs are employed as drug carriers for diseases like cancer because of their small size and increased stability. In addition, they have several desirable properties that make them ideal for treating bone cancer, including high stability, specificity, higher sensitivity, and efficacy. Furthermore, they might be taken into account to permit the precise drug release from the matrix. Drug delivery systems for cancer treatment have progressed to include nanocomposites, metallic NPs, dendrimers, and liposomes. Materials’ mechanical strength, hardness, electrical and thermal conductivity, and electrochemical sensors are significantly improved using nanoparticles (NPs). New sensing devices, drug delivery systems, electrochemical sensors, and biosensors can all benefit considerably from the NPs’ exceptional physical and chemical capabilities. Nanotechnology is discussed in this article from a variety of angles, including its recent applications in the medical sciences for the effective treatment of bone cancers and its potential as a promising option for treating other complex health anomalies via the use of anti-tumour therapy, radiotherapy, the delivery of proteins, antibiotics, and vaccines, and other methods. This also brings to light the role that model simulations can play in diagnosing and treating bone cancer, an area where Nanomedicine has recently been formulated. There has been a recent uptick in using nanotechnology to treat conditions affecting the skeleton. Consequently, it will pave the door for more effective utilization of cutting-edge technology, including electrochemical sensors and biosensors, and improved therapeutic outcomes.
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