Cancer is characterized by the development of abnormal cells that divide uncontrollably, have the ability to invade and destroy normal body tissue, and often spread throughout the body. One of the most common cancers in terms of prevalence and mortality worldwide is lung cancer, with more than 2.2 million new cases of lung cancer in 2020, which is 12.5% of the total cancer statistics, so the 5-year survival rate is about 16 [1]. In Iran, the number of lung cancer cases in men and women in 2020 was approximately 10,465 (12.6%), and the number of deaths was 9,071 (10.9%) [11]. The main types of lung cancer include small cell lung cancer (SCLC), which has a faster growth and spread rate, and non-small cell lung cancer (NSCLC), which pathologically accounts for 80% of cases. There are 3 main groups of adenocarcinoma (ADC) with a frequency of 30–40%, which is the most common form of NSCLC, squamous cell carcinoma (SCC), and large cell carcinoma (LCC). The people who are more likely to develop lung cancer are people over 50 years of age with a smoking history. The main risk factors involved in lung cancer are tobacco consumption, air pollution, being exposed to substances such as asbestos or radon at home or work, and having a family history of lung cancer [3] [4]. Common treatments for lung cancer include chemotherapy, radiation therapy, surgery, and targeted molecular treatments [3]. Currently, most of the anti-cancer treatments with all the desired efficiency are associated with many undesirable and unfortunate side effects. Inefficiency, lack of safety, drug resistance, and high costs of treatment have led to a lack of trust in these methods. For this reason, today, returning to the use of medicinal plants has received a lot of attention, and since products of plant origin are naturally They are multi-purpose, and in addition, compared to chemical agents, they are cheap and safe. Also, the active substances in herbal medicines have a biological balance due to their combination with other substances, so they are not accumulated in the body and have no side effects. There are fewer side effects, and in this sense, they are significantly superior to chemical drugs [1] and [8]. One of these medicinal plants, Drimia maritima, with the scientific name Urginea maritima, has been used since ancient times to treat various diseases, including respiratory diseases, heart defects, skin problems, and digestive disorders [1] [9]. Among the main active compounds, unique bufadienolides such as Proscillaridin A, which is a type of cardiac glycoside drug, can be used in the treatment of congestive heart failure and cardiac arrhythmia. The cardiotonic effect of cardiac glycosides is caused by their anti-Na/K pump activity; although originally prescribed for heart failure, their anticarcinogenic effect was recently discovered [9] [4]. According to studies, Proscillaridin at very low concentrations effectively induces apoptosis and potently inhibits cell survival pathways while having very little toxicity to normal cells [10]. Apoptosis (programmed cell death) is triggered through different pathways; some of these pathways occur due to the activation of caspase group enzymes. BAX and BCL2 genes are among the important genes involved in the mitochondrial pathway of apoptosis, since the balance between proliferation and apoptosis is disrupted in cancer cells, and cells need to inhibit apoptosis for their growth and proliferation, a direct relationship. There is a relationship between the expression of these genes and the cancerous process, so investigating the expression changes of these genes can be considered a therapeutic or diagnostic goal in cancer studies [11] [12].
Among the plants that have been of great interest due to the presence of natural and safe active ingredients is the turmeric plant, with the scientific name Curcuma longa. Turmeric has been used for thousands of years in the treatment of various diseases such as colds, fevers, skin diseases, and liver diseases, and its use is not toxic even in high doses. Recently, this substance has been considered an effective combination for the treatment of cancer [15] [16]. Turmeric itself consists of three main compounds: demethoxycurcumin, curcumin, and bisdemethoxycurcumin. Among these components, curcumin, the effective ingredient of the rhizome of the turmeric plant, is beneficial in preventing the growth of cancer cells. This compound has anti-inflammatory, anti-viral, anti-bacterial, anti-fungal, and anti-cancer properties [16]. Many in vitro and in vivo studies have shown that curcumin can inhibit cancer in three stages: progression, angiogenesis, and tumor growth. The anticancer activities of proscillaridin and curcumin are through their effects on various biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumors, and cell metastasis [18]. The purpose of this research is to simultaneously investigate the effectiveness of proscillaridin and curcumin in inducing apoptosis and cell cycle changes in NSCLC cells.