Abstract
Datura innoxia is an important species of Solanaceae family with several purposes in folk medicine. This study intends to explore the cytotoxic effect of D. innoxia on various cancer cell proliferation. D. innoxia ethanolic extract’s effect on the progression of the cell cycle and the induction of apoptosis were investigated by flow cytometry. Further, real-time PCR was employed to confirm apoptosis initiation. In addition, active phytochemicals of D. innoxia was identified by gas chromatography–mass spectroscopy (GC-MS). The cell viability study revealed that the ethanolic extract of D. innoxia demonstrated potent cytotoxicity, with an IC50 value of 10 μg/mL against LoVo colon cancer cells. Cell cycle staining with propidium iodide revealed that D. innoxia treatment leads to cell accumulation in the sub-G1 phase. Using the Annexin V-FITC/PI assay, the ethanolic extract was found to cause a dose-dependent increase in early and late apoptosis when compared to control cells. Apoptosis as the mode of cell death was also confirmed by the increased expression of p53, bax and caspase-8, -9, and -3 along with downregulation of Bcl-2. GC-MS analysis displayed that 3,5-Dihydroxybenzoic acid (16.53%), heneicosyl formate (14.14%), 2,3-dimethyl-3-pentanol (12.89%), 2-hydroxy-4-methyl pentanoic acid (5.19%) were the main phytoconstituents. These findings conclude that D. innoxia causes cell death through apoptosis, suggesting more attention should be paid to further exploration of the active components from D. innoxia responsible for the observed activities.
Highlights
Cancer is still a major health issue, and the incidence of cancer related deaths is increasing around the globe [1]
The results of the present study presented that the D. innoxia ethanolic extract exerted a cytotoxic effect on various cancer cells, with high potent activity against LoVo human colon cancer cells
Our results clearly proved that the extract treatments led to a decrease in the antiapoptotic Bcl-2 gene and an increase in the proapoptotic Bax gene, as well as activating caspase genes in the treated groups compared to the control, suggesting that D. innoxia acts through a caspase-dependent apoptosis pathway
Summary
Cancer is still a major health issue, and the incidence of cancer related deaths is increasing around the globe [1]. The female breast, lung and colorectal cancers types are among the most commonly diagnosed cancers globally and continue to be the leading cause of cancer related death worldwide [2]. Mainly unsuccessful and leading to many deaths due to their side effects, the use of conventional treatments to treat cancer is still the most common option of treatment. The development of new drugs from natural sources with fewer side effects is becoming promising field in cancer research [3]. Plants are still a promising reservoir for a novel chemical compound in the cancer research area [4]. Many well-known anticancer drugs, such as paclitaxel and camptothecins, are isolated from plant-derived products [5]. With a different biogeographic region, Saudi Arabia provides a remarkably rich source for medicinal plants that have anticancer properties [6,7]
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