## 1 Introduction  
Lung cancer causes more than 25% of cancer-related mortality among all cancer types, and 80% of these lung cancer cases are non-small cell lung cancer (NSCLC) [1]. Besides, lung cancer's 5-year relative survival rate is comparatively low than the other leading cancer sites (17.4%) [2]. The two main aspects that restrict the efficacy of chemotherapy are its toxicity [3] and the development of resistance [4]. Particularly in the advanced stages of lung cancer, chemotherapeutic drug resistance cannot achieve adequate results and is the primary factor considered to cause more than 90% of treatment failures [5]. Traditional medicine utilizes the broad-spectrum pharmacological effects of multiple ingredients to influence multiple targets [6]. With clinical applications and evidence gathered over thousands of years, traditional medicine has recently attracted increasing attention for its effectiveness and fewer side effects [7]. In recent years, with the advancement of translational science and molecular biology, herbal remedies and combinational formulas are being tested in both preclinical and clinical trials as viable treatment options for various malignancies [8]. Thus, it might be advantageous to identify and develop natural compounds, active ingredients, single herbs and combinational formulas in traditional medicine that could influence diverse signaling pathways on the tumor while minimizing side effects compared to other conventional therapies.  
_Artemisia santoliniida_ is one of the species of the genus _Artemisia_ that forms a mono-dominant shrub layer common in stony or disturbed lower-montane sites throughout Central Asia south of the Himalayas [9]. The genus _Artemisia_, often known collectively as wormwood, is a large and diverse genus belonging to the daisy family Asteraceae and encompasses around 500 species of herbs and shrubs [10; 11; 12]. They are frequently used to treat hepatitis, diabetes, malaria, laryngitis, pharyngitis, hemorrhaging, rheumatoid arthritis, and fungal, bacterial, and viral infections [11; 13; 14; 15; 16; 17; 18]. Although _A. santoliniida_ is ubiquitous in Central Asia, very few studies have been conducted on this species, and its biology is poorly known [19]. In addition, the anticancer activities of other _Artemisia_ species, including _A. vulgaris_ in human colon cancer cells, _A. scoparia_ against NSCLC cell line, and _A. aucheri_ and _A. annua_ extracts have also been scientifically validated [20; 21; 22; 23]. However, the antiproliferative role of _A. santoliniida_ in NSCLC and the possible underlying mechanisms have not yet been reported.  
This study aimed to shed light on the mechanisms of action of ASE toward NSCLC. With a motivation to elucidate the characterization changes that occurred in NSCLC responsible for ASE anticancer activity upon exposure, microscopic visualization and flow cytometric analysis were performed. Additionally, the corresponding gene expression changes related to the distinct patterns of cell death were assessed using Western blot analysis. Here, our group reports the selectivity ASE in triggering diverse cell death modes via affecting multiple mediators for the first time. We hypothesized that the anticancer properties of ASE may be due to the inhibition of pro-survival protein expressions in NSCLC.