The anticancer and anti-inflammatory effects of polyherbal drug AS20 on HeLa cells resistant to 5-Fluorouracil

Cancer treatment that involves chemotherapy often results in developed drug resistance which can be a major deterrent for the success of a treatment protocol. Increased inflammation, due to the drug's presence, contributes to disease progression and increased Cyclooxygenase-2 (COX2) expression (inflammatory marker). Integrative oncology is a field that focuses on combining natural herbal formulations with standard care to provide optimal clinical outcomes in a holistic manner, to minimize side effects, and to overcome drug resistance, including inflammation. 5-Flurouracil (5-FU) is a chemotherapeutic medication used to treat cancers. We studied drug resistance by deriving 5-FU-resistant HeLa cells (HeLa R) and evaluating the efficacy of AS20 in in vitro experiments. AS20 is an herbal formulation derived from the plant Amaranthus spinosus, an indigenous plant found in India. It contains different types of secondary metabolites such as saponins, polyphenols, alkaloids, terpenoids, and flavonoids. We hypothesized that AS20 has anti-inflammatory and anticancer properties on HeLa R. We investigated if AS20 could downregulate increased inflammatory markers such as COX2 in HeLa R. Also, we studied anti-apoptotic and pro-apoptotic genes in AS20 treated HeLa R cells. Our results demonstrated that the inhibitory concentration at 50% (IC50) values of HeLa wild type cells with AS20 treatment was significantly less than HeLa R cells. Also, AS20 brought down induced COX2 expression in HeLa R cells. AS20 treatment on HeLa R cells showed upregulation of BAX (pro-apoptotic) but no significant change in BAD (pro-apoptotic) and downregulation of BCL2 and BCL2L1 (anti-apoptotic genes) in HeLa R cells. Our results showed that AS20 has anti-inflammatory and pro-apoptotic properties when treated on HeLa R cells.