Evaluating in vitro cytotoxic effects of Artemisia afra and Artemisia annua infusions against selected lung cancer cell lines

Abstract

Lung cancer was the leading cause of cancer deaths in 2020. This can mainly be attributed to the poor outcomes of chemotherapy as a result of acquired multidrug resistance. Traditional medicinal plant species such as Artemisia afra and A. annua have been used for decades to treat various health-related conditions, including cancer. Both species have previously exhibited anti-cancer activity, although studies to confirm their efficacy and safety in the treatment of lung cancer are still lacking. Therefore, the aim of this study was to identify the major compounds in the traditionally prepared infusions and to evaluate the infusions’ in vitro cytotoxicity against the following lung cancer cell lines: H69V, a chemo-sensitive small cell lung cancer (SCLC) line; H69AR, a drug-resistant SCLC line that hyper-expresses the multidrug resistance-associated protein 1 efflux transporter; and A549, a non-small cell lung cancer line. Non-cancerous lung fibroblast and kidney cells (MRC-5 and Vero) were also included in the study to evaluate the cancer selectivity of the samples. A series of concentrations of each of the samples were screened to determine the relative cell viability inhibitory concentration and selectivity index by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The major phytochemicals in the infusions were identified as organic acids and coumarins and both A. annua and A. afra infusions showed a high degree of selectivity towards the chemo-sensitive H69V cells with IC 50 values of 6 and 70 µg/mL, respectively, and a SI value of 10 for A. afra . However, cytotoxicity towards both non-cancerous cell lines was also observed. Furthermore, the H69AR cells showed considerable resistance to the plant extracts’ cytotoxicity, suggesting that some of the active phytoconstituents in the extracts may potentially be substrates of the MRP1 efflux transporter. From the outcomes of this study, it became evident that both A. afra and A. annua extracts have the potential as a treatment for chemosensitive SCLC. However, possible non-selective cytotoxic effects may be a concern that warrants further investigation. • The cancer cytotoxicity of infusions from Artemisia annua and A. afra was evaluated. • The major compounds in the infusions were identified as organic acids and coumarins. • Infusions were found to be active at > 50 µg/mL with A. afra being most active. • While less active than paclitaxel, A . afra was more selective against H69V and A549.