Evaluating the Anti-Tumor Efficacy and Safety of AEV01 in Glioblastoma and Hepatocellular Carcinoma: AnIn VitroandIn VivoApproach

Abstract

Background: Gliomas and hepatocellular carcinoma (HCC) are difficult to treat with short survival rates despite current therapies. The need for new treatments is urgent, and orthotopic cell-derived tumor xenograft (CDX) models have provided valuable insights. AEV01, a specialty extract from the roots of Picrorhiza kurroa, shows promise as a non-surgical treatment option with anti-inflammatory, antioxidant, and anti-cancer properties. Its efficacy has been demonstrated in a patient with pancreatic cancer and in enhancing immune conditions in COVID-19 patients. Objectives: This study was conducted with the objective to investigate the anti-tumour properties of AEV01 in human glioblastoma and liver cancer cells through in vitro and in vivo experiments. Methodology: The methodology of the study involved the use of various cell lines including HEK-293T, U-87 MG glioblastoma, HepG2 liver cancer, Hep3B, and WRL-68 liver senescence cells. The cytotoxicity of the drug AEV01 was assessed using the MTT assay. Dual staining with acridine orange/ethidium bromide was performed to evaluate morphological changes in the cancer cells. ELISA was used to detect protein marker expression levels. Immunocytochemistry was employed to assess CD36 expression in various cellular models. Orthotopic tumor engraftment was carried out to establish a glioblastoma-induced model. Animal grouping and treatment plans were done, and histopathological effects were evaluated. Immunohistochemistry was performed to assess the anti-tumor effects of AEV01. ELISA and toxicity studies were also conducted. Results: The results of the study showed that AEV01 had dose-dependent cytotoxicity against glioma and liver cancer cells, while minimally impacting normal cells. AEV01 induced apoptosis in cancer cells and downregulated the expression of inflammatory markers while upregulating the expression of the tumor suppressor protein TP53. AEV01 also decreased the expression of CD36, a potential target for cancer therapy, in glioma and liver cancer cells. In an in vivo glioma-induced model, AEV01 exhibited anti-tumor effects and reduced the expression of CD36. Histopathological analysis demonstrated that AEV01 had minimal toxicity on vital organs. Overall, these findings suggest that AEV01 has potential as a therapeutic agent for glioma and liver cancer.