_Applied_  
_sciences_  
_Article_  
**Comparative Evaluation of Apoptosis Induction Using Needles, Bark, and Pollen Extracts and Essential Oils of _Pinus elalarica_ in Lung Cancer Cells**  
**[PERSON] 1**, **[PERSON] 2, [PERSON] 3, [PERSON] 4, [PERSON] 5, [PERSON] 6, [PERSON] 7, [PERSON] 5,* and [PERSON] 6,*(r)  
and lymphatic systems. Cancer is the second leading cause of death worldwide and was reportedly responsible for 9.6 million deaths in 2018 [1]. Among these, lung cancer is the most commonly diagnosed cancer (11.6% of all cases), ranking first in terms of reported cancer deaths (18.4% of all cancer deaths) [1]. Throughout the history of human life, natural products derived from living organisms such as plants have been utilized as a primary source of medicinal agents [2]. Plants provide an extensive reservoir of therapeutic agents, representing a significant structural variety and remarkable chemical entities in modern medicine. Numerous studies have also reported that natural products derived from plants possess anticancer properties [3].  
Gymnosperms are seed-bearing vascular plants, including cycads, ginkgo, Jews, and conifers, in which the ovules or seeds are not enclosed within the ovary. Pinostrobin, pycrogenol, enzogenol, and pinocembrin are important anticancer agents of gymnosperm origin. Paclitaxel (taxol), isolated from the bark of yeew trees (_Taxus_ sp.), is reportedly cytotoxic to human prostate, ovarian, breast, and lung cancer cells [4; 5]. The _Pinus_ genus is the largest in the family Pinaceae [6]. These coniferous, evergreen, and typically monoecious trees are cultivated in most areas of the Northern Hemisphere [7]. _Pinus_ _el'arica_, also named Tehran pine, is native to the South Caucasus between Europe and Asia and has been extensively grown in Iran. In traditional medicine, different parts of this plant (bark, needles, and nuts) have been used for the treatment of several conditions, including skin wounds, bronchial asthma, dermatitis, and skin irritation, and have reportedly shown antibacterial, antimutagenic, antitumor, anti-inflammatory, and glucose-lowering activities [8; 9; 10; 11]. Essential oils and extracts from pine needles and bark are rich in terpenoids such as cyanophylle, limonene, \(\alpha\)-pinene, and phenolic acids [12; 13; 14]. Pine extracts act as antioxidants by reacting with free radicals, thus protecting DNA against oxidative damage and apoptosis induced by hydroxyl radicals [15; 16; 17]. phytochemical evidence has revealed that pine extracts contain catechin and taxifolin, two polyphenic compounds that afford a potent anticancer product, Pycrogenol(r)[8; 18]. Apoptosis plays an important role in modulating immunological competency, development, and homeostasis through changes in cell morphology, chromatin condensation, DNA fragmentation, caspase-3 activation, Bax and p53 elevation, Bcl-2 reduction, and poly (ADP-ribose) polymerase (PARP) cleavage [19]. For instance, a pinecone extract of _Pinus_ _koriensis_ has revealed a beneficial effect in cancer prevention by inducing apoptosis in lung cancer cells through caspase-3 activation [20]. Therefore, induction of apoptosis in cancer cells with plant-derived products can be employed as an effective strategy against tumor development.  
Several studies have reported the pharmacological properties and chemical diversity of _P. eldarica_ extracts; however, the antineoplastic effects of _P. eldarica_ against human lung cancer cells and their underlying mechanisms of action are yet to be reported. In the present study, we aimed to evaluate the antioxidant, cytotoxic, and proapoptotic effects of hexane, methanolic, and aqueous extracts, and essential oils, of various parts (bark, needles, and pollen) of _P. eldarica_ on lung cancer (A549) cells, with the possible elucidation of cellular and molecular mechanisms. The results of this study could help pave the way for developing novel cancer therapeutic agents, opening new horizons for the application of natural products in lung cancer therapy.