Osteosarcoma is the most common primary bone cancer affecting children and adolescents worldwide. Despite an incidence of three cases per million annually, it accounts for an inordinate amount of morbidity and mortality. While the use of chemotherapy (cisplatin, doxorubicin, and methotrexate) in the last century initially resulted in marginal improvement in survival over surgery alone, survival has not improved further in the past four decades. Patients with metastatic osteosarcoma have an especially poor prognosis, with only 30% overall survival. Hence, there is a substantial need for new therapies. The inability to control the metastatic progression of this localized cancer stems from a lack of complete knowledge of the biology of osteosarcoma. Consequently, there has been an aggressive undertaking of scientific investigation of various signaling pathways that could be instrumental in understanding the pathogenesis of osteosarcoma. Here, we review these cancer signaling pathways, including Notch, Wnt, Hedgehog, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT, and JAK/STAT, and their specific role in osteosarcoma. In addition, we highlight numerous natural compounds that have been documented to target these pathways effectively, including curcumin, diallyl trisulfide, resveratrol, apigenin, cyclopamine, and sulforaphane. We elucidate through references that these natural compounds can induce cancer signaling pathway manipulation and possibly facilitate new treatment modalities for osteosarcoma.

Purpose Several formulations have been proposed to improve the systemic delivery of novel cancer therapeutic compounds, including cyclodextrin derivatives. We aimed to synthesize and characterize of CDF-β-cyclodextrin inclusion complex (1:2) (CDFCD). Methods The compound was characterized by Fourier transform infrared, differential scanning calorimetry, powder X-ray diffraction studies, H1 & C13 NMR studies and scanning electron microscopic analysis. Its activity was tested against multiple cancer cell lines, and in vivo bioavailability was checked. Results CDF-β-cyclodextrin was found to lower IC₅₀ value by half when tested against multiple cancer cell lines. It preferentially accumulated in the pancreas, where levels of CDF-β-cyclodextrin in mice were 10 times higher than in serum, following intravenous administration of an aqueous CDF-β-cyclodextrin preparation. Conclusions Novel curcumin analog CDF preferentially accumulates in the pancreas, leading to its potent anticancer activity against pancreatic cancer cells. Synthesis of such CDF-β-cyclodextrin self-assembly is an effective strategy to enhance its bioavailability and tissue distribution, warranting further evaluation for CDF delivery in clinical settings for treatment of human malignancies.

Benzoquinones are class of natural quinones found chiefly in higher plants, fungi, bacteria and animal kingdom. They are involved in important biological functions such as bioenergetic transport, oxidative phosphorylation and electron transport processes. In recent years it has become increasingly clear that some of them possess potent antioxidant, anti-inflammatory and anticancer activities. There is clearly a common thread running through these activities and there have been a large number of studies carried out to unravel the mechanisms of these activities. In the present review we have provided a brief account of these studies especially covering these aspects. Although antioxidant potentials of these compounds constitute the basis of their biological activities its nature and scope is dictated by many microscopic biological environments. One of the important advantages offered by these compounds is the ease with which they can be synthesized and chemically manipulated. This can easily provide impetus for further research in developing some potentially useful drug molecules.