Crocin, a bioactive molecule of saffron, inhibited proliferation of both HCT116 wild-type and HCT116 p53?/? cell lines at a focus of 10 mM. upsurge in the DNA damage-sensor deposition, H2AX indicating that crocin induced an autophagy-independent traditional programmed cell loss of life. L.) can be used being a colouring or flavoring agent and its own constituents typically, including crocin, crocetin, picrocrocin, and safranal, possess all demonstrated wellness promoting properties. Although some research support the idea that saffron may be a guaranteeing cancers therapy agent, its detailed molecular systems lack still. Saffron was also suggested as an excellent apoptotic inducer of tumor cells. Saffrons ability to induce Tmem1 apoptosis has been reported to play a crucial role in the death of human cervical carcinoma cells (HeLa), human hepatocellular carcinoma cells (HepG2), and human colorectal malignancy cells [6,7,8]. studies have shown that saffrons major carotenoid, crocin, is regarded as the most promising anticancer compound in saffron as it has been reported to have inhibitory effects against a wide range of Succinyl phosphonate trisodium salt malignancy cells including human cervical carcinoma HeLa cells, adenocarcinoma cells, and different forms of breast malignancy cells [9,10]. Several groups have reported that most of the cellular systems in which autophagy was proven to contribute to cell death had defects in the apoptosis signaling pathway [5,11,12]. To that end, the tumor suppressor protein p53 is known to induce and/or repress the expression of target genes involved in central pathways, such as control of the cell cycle and apoptosis [13]. p53 triggers cell cycle arrest and hence allows DNA damage repair or promotes apoptosis if cells are challenged with severe irreparable insults [14]. Mutations in the p53 gene are detected in most CRCs and are thought to be late events in the transition from dysplastic adenomas to invasive carcinomas [15,16]. The connection between autophagic and apoptotic cell death within the context of cancer continues to be unresolved. Autophagy provides cancers cells using a defensive response under unfavorable circumstances [17]. During mobile stress, cells make use of autophagy to adjust to the microenvironment, but autophagy because of excessive stress results in cell loss of life [18,19,20]. Alternatively, several studies have got reported that autophagy is usually triggered in some cancers in response to numerous anticancer brokers, including As2O3, tamoxifen, and temozolomide [21,22,23]. The cellular function of autophagy remains a matter of argument, and its role in cancers Succinyl phosphonate trisodium salt is still particularly controversial [20]. This study is set to expose crocin as a potential chemotherapeutic agent for colorectal malignancy where the molecular mechanism through which crocin induces cell death in two p53 isogenic HCT116 cells is usually investigated. Our results unveil a novel mechanism of action of crocin in inducing autophagy and/or apoptosis in human colon cancer cells in a p53-dependent manner. 2. Results 2.1. Crocin Inhibits Proliferation of HCT116 Cell Lines The effect of crocin on HCT116 cell lines cell viability was examined by MTT analysis. Crocin reduced proliferation in a time- and dose-dependent manner. Physique 1A,B show a significant, but different cell proliferation inhibition ( 0.05) of both HCT116 wild-type and HCT116 p53?/? cell lines at a concentration of 10 mM of crocin after 24 h, of 40% and 65%, respectively. However, both cell lines showed the same pattern of reduced cell proliferation (65%) after 48 h of crocin treatment. To justify this result, trypan blue staining was conducted for both cell lines treated with 10 mM crocin for 24 and 48 h. Indeed, crocin induced more cell death among the Succinyl phosphonate trisodium salt surviving 30% (Physique 1B) HCT116 p53?/? cells compared to HCT116 wild-type cells after 24 and 48 h (Amount 1C,D). That is in contract using a prior study displaying that crocin-mediated cell viability inhibition was suffering from p53 position [24]. Open up in another window Open up in another window Amount 1 Aftereffect of raising concentrations of crocin over the development of HCT116 wild-type (wt) and HCT116 p53?/? cells for 24 and 48 h. (A,B) Viability check evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) displaying the HCT116 wild-type and HCT116 p53?/? cells neglected (ctrl) or treated with different concentrations of crocin (Cro; 0.5 to 15 mM) for 24 and 48 h. The MTT data proven are performed in quadruplicates; and (C) Cell quantities (inactive and alive) and (D) cell.