No abstract

Despite the advances made in cancer therapeutics, their adverse effects remain a major concern, putting safer therapeutic options in high demand. Since chalcones, a group of flavonoids and isoflavonoids, act as promising anticancer agents, we aimed to evaluate the in vivo anticancer activity of a synthetic isoquinoline chalcone (CHE) in a mice model with Ehrlich solid carcinoma. Our in vivo pilot experiments revealed that the maximum tolerated body weight-adjusted CHE dose was 428 mg/kg. Female BALB/c mice were inoculated with Ehrlich ascites carcinoma cells and randomly assigned to three different CHE doses administered intraperitoneally (IP; 107, 214, and 321 mg/kg) twice a week for two consecutive weeks. A group injected with doxorubicin (DOX; 4 mg/kg IP) was used as a positive control. We found that in CHE-treated groups: (1) tumor weight was significantly decreased; (2) the total antioxidant concentration was substantially depleted in tumor tissues, resulting in elevated oxidative stress and DNA damage evidenced through DNA fragmentation and comet assays; (3) pro-apoptotic genes p53 and Bax, assessed via qPCR, were significantly upregulated. Interestingly, CHE treatment reduced immunohistochemical staining of the proliferative marker ki67, whereas BAX was increased. Notably, histopathological examination indicated that unlike DOX, CHE treatment had minimal toxicity on the liver and kidney. In conclusion, CHE exerts antitumor activity via induction of oxidative stress and DNA damage that lead to apoptosis, making CHE a promising candidate for solid tumor therapy.

In cancer, angiogenesis is a hallmark necessary to supply sufficient nutrients for tumor growth and metastasis to distant sites. Therefore, targeting tumor angiogenesis emerges as an attractive therapeutic modality to retard neoplastic cell growth and dissemination using classes of anti-angiogenic drugs. However, multiple administrations of these drugs show adverse effects, precluding their long-term usage. Conventional chemotherapeutic drugs, natural compounds, carbon-based materials, inorganic and metallic elements, genes, siRNAs, shRNAs, and microRNAs can be incorporated into nanovehicles (e.g. polymers) for delivery to specific targets. This chapter reviews angiogenesis and the underlying molecular mechanisms that regulate this process. Furthermore, this chapter provides an overview on different formulations of nanoparticles or nanovectors that employed to combat cancer, with a special focus on their therapeutic potentials in the context of the suppressive effects on tumor angiogenesis process using in vitro and in vivo models of different tumor entities.