*Article* **Phytochemical Analysis and Anticancer Properties of** *Drimia maritima* **Bulb Extracts on Colorectal Cancer Cells**

**Khairallah Al-Abdallat 1,2,†, Maher Obeidat 3,†, Nidaa A. Ababneh 3, Suzan Zalloum 4, Sabal Al Hadidi 4, Yahya Al-Abdallat 5, Malek Zihlif <sup>6</sup> and Abdalla Awidi 3,7,\***

	- <sup>3</sup> Cell Therapy Center, The University of Jordan, Amman 11942, Jordan

**Abstract:** Cancer is a worldwide health problem and is the second leading cause of death after heart disease. Due to the high cost and severe side effects associated with chemotherapy treatments, natural products with anticancer therapeutic potential may play a promising role in anticancer therapy. The purpose of this study was to investigate the cytotoxic and apoptotic characteristics of the aqueous *Drimia maritima* bulb extract on Caco-2 and COLO-205 colorectal cancer cells. In order to reach such a purpose, the chemical composition was examined using the GC-MS method, and the selective antiproliferative effect was determined in colon cancer cell lines in normal gingival fibroblasts. The intracellular ROS, mitochondrial membrane potential, and gene expression changes in selected genes (*CASP8*, *TNF-α*, and *IL-6* genes) were assessed to determine the molecular mechanism of the antitumor effect of the extract. GC-MS results revealed the presence of fifty-seven compounds, and Proscillaridin A was the predominant secondary metabolite in the extract. The IC50 of *D*. *maritima* bulb extract on Caco-2, COLO-205, and the normal human gingival fibroblasts were obtained at 0.9 μg/mL, 2.3 μg/mL, and 13.1 μg/mL, respectively. The apoptotic effect assay indicated that the bulb extract induced apoptosis in both colon cancer cell lines. *D. maritima* bulb extract was only able to induce statistically significant ROS levels in COLO-205 cells in a dose-dependent manner. The mitochondrial membrane potential (MMP) revealed a significant decrease in the MMP of Caco-2 and COLO-205 to various concentrations of the bulb extract. At the molecular level, RT-qPCR was used to assess gene expression of *CASP8*, *TNF-α*, and *IL-6* genes in Caco-2 and COLO-205 cancer cells. The results showed that the expression of pro-inflammatory genes *TNF-α* and *IL-6* were upregulated. The apoptotic initiator gene *CASP8* was also upregulated in the Caco-2 cell line and did not reach significance in COLO-205 cells. These results lead to the conclusion that *D*. *maritima* extract induced cell death in both cell lines and may have the potential to be used in CRC therapy in the future.

**Keywords:** colorectal; *Drimia maritima*; anticancer
