**1. Introduction**

Cancer is a disease characterized by constant clonal proliferation of the somatic cells due to which the homeostatic feedback mechanism gets out of control through genetic and epigenetic alterations and kills by invading normal tissues [1–4]. Natural products extracted from plants, microbes, and other marine organisms have secondary or non-essential metabolism. Natural products have gained importance in novel anticancer agents' discovery and investigation of more effective drugs [5, 6]. Colchicine, which is obtained from plants of the genus Colchicum belonging to Liliaceae (Colchicaceae) family, is one of the natural product. Colchicine is an anti-neoplastic drug used in cancer therapy as a mitotic inhibitor [7].

Apoptosis plays a critical role in the elimination of damaged or undesirable cells and the development and maintenance of homeostasis. Disturbances in these processes cause various diseases ranging from cancer and autoimmune disorders to ischemic injuries and neurodegenerative diseases [8–14].

Apoptosis is encouraged by cell signaling, lack of growth factors, the release of granzyme, specific receptor-ligand interactions, and various stress factors (chemotherapy, radiation, etc.). Then, the cell death process is initiated. Some of the original proteins play a role in this process. As a consequence thereof, signals are transferred to the execution mechanism with the help of adaptor proteins and are regulated the mitochondrial permeability by bcl-2 family proteins. An increase in permeability of the outer mitochondrial membrane is caused by the release of cytochrome c. Cytochrome c is connected to apoptosis protease activation factor (Apaf-1) in the cytosol. Apaf-1 binds to the pro-caspase-9 molecule by oligomerization in the presence of adenosine triphosphate (ATP) and constitutes apoptosome. The activated caspase-9 plays a role in the activation of caspase-3 and caspase-7. Nevertheless, the *bcl-2* in the mitochondrial membrane prevents activation of caspases by preventing the increase of mitochondrial permeability and making stable Apaf-1 and so on proteins. Thus, apoptosis does not occur. *bcl-xL,* which is a member of the bcl-2 family, and *bcl-2* play the anti-apoptotic role. *bax*, *bad,* and *bak* are triggered by apoptosis [15–22].

In recent years, investigating the molecular mechanisms of apoptosis by using agents has become extremely important in cancer treatment [23–26]. Our study is aimed to investigate the cytotoxic effects of different concentrations of two extracts that belong to the genus *Colchicum*, one of them is endemic in Turkey (*Colchicum umbrosum* Steven (S.) and *Colchicum baytopiorum* CD Brickell (CD) is an endemic species in Turkey [27, 28], on HeLa cells and also show the molecules that play a role in the regulation of molecular mechanisms of the resultant apoptosis.
