Micromeria fruticosa Induces Cell Cycle Arrest and Apoptosis in Breast and Colorectal Cancer Cells

Abstract

Micromeria fruticosa (L.) Druce subsp. serpyllifolia (Lamiaceae) has been used widely in folk medicine to alleviate various ailments such as abdominal pains, diarrhea, colds, eye infections, heart disorders and wounds. A few reports have confirmed different therapeutic potentialities of its extracts, including the anti-inflammatory, gastroprotective, analgesic, antiobesity and antidiabetic activities. This study aimed to investigate the mechanistic pathway of the antiproliferative activity of the ethanolic extract of M. fruticosa on two different cancer cell lines, namely human breast (mammary carcinoma F7 (MCF-7)) and human colorectal (human colon tumor cells (HCT-116)) cell lines. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay, Annexin V-FITC/PI, caspases 8/9 and cell cycle analyses, qRT-PCR and Western blot were used to assess the effect of M. fruticosa on cytotoxicity, apoptosis, cell cycle, cell cycle-related genes and protein expression profiles in MCF-7 and HCT-116. The extract inhibits cell proliferation in a time- and dose-dependent manner. The half-maximal inhibitory concentration (IC50) for both cell lines was found to be 100 μg/mL. Apoptosis induction was confirmed by Annexin V-FITC/PI, that was related to caspases 8 and 9 activities induction. Furthermore, the cell cycle analysis revealed arrest at G2/M phase. The underlying mechanism involved in the G2/M arrest was found to be associated with the downregulation of CDK1, cyclin B1 and survivin that was confirmed by qRT-PCR and Western blotting.

Comprehensive circular RNA expression profiling constructs a ceRNA network and identifies hsa_circ_0000673 as a novel oncogene in distal cholangiocarcinoma

“…For example, the protein encoded by CCNB1 plays a crucial role in regulating the G2/M transition. In gastric, breast, and colorectal cancer cells, inhibition of CCNB1 induced G2/M phase cell cycle arrest and promoted apoptosis [ 29 , 30 ]. Furthermore, CHEK1 [ 31 ], BUB1B [ 32 ], and MCM2 [ 33 ] could promote cancer cell proliferation, and which were enriched in cell cycle pathways in GSEA analysis for CCA.…”

An In Vitro Evaluation of the Molecular Mechanisms of Action of Medical Plants from the Lamiaceae Family as Effective Sources of Active Compounds against Human Cancer Cell Lines

“…Progression is mediated by the activation and deactivation of cyclin-dependent kinases (CDKs), while activation depends on the presence of activated subunits named cyclins. The levels of cyclins and CDKs are changed in human cancers; for example, the levels of CDK1 and cyclin B1 are reduced in human breast adenocarcinoma (MCF-7) and human colorectal cancer (HCT-116) cell lines following treatment with Micromeria fruticosa aerial part extract, resulting in G2/M arrest [ 143 , 144 ]. In addition, treatment with Melissa officinalis leaf extract blocked the expression of CDKs 2, 4, and 6 and cyclin D3 in the human colon carcinoma (HT-29 and T84) cell lines, and specifically activated an important CDK inhibitor named p18 [ 145 ]; in addition, treatment with Vitex rotundifolia fruit extract downregulated cyclin D1 and CDK 4 levels in HCT-116 and human colon adenocarcinoma (SW480) [ 146 ].…”

“…The attachment of a Fas to a specific receptor triggers the formation of specific death-inducing signaling complex (DISC) possessing a Fas-associated death domain (FADD); this complex can recruit an adaptor protein and then activate initiator caspase-8 and caspase-10. Caspase-8 induction was found to induce apoptosis in MCF-7 and HCT-116 cells following Micromeria fruticose aerial part extract administration [ 144 ], as well as treatment with Vitex rotundifolia leaf extract in T-47D cells [ 159 ], Stachys pilifera leaf extract in the HT-29 cell line [ 154 ], and for Teucrium chamaedrys aerial flowering part extract in SW480 cells [ 170 ]. In addition, it was speculated that Satureja khuzistanica extract enriched in rosmarinic acid can induce apoptosis through activation of the extrinsic pathway in MCF-7 cells [ 151 ].…”

“…This protein is under-expressed in cancer cells and is related to poor clinical outcome through the blockage of apoptosis by caspase inhibition [ 178 ]. Significant reductions of survivin levels were observed for Micromeria fruticosa aerial part extract in MCF-7 and HCT-116 cell lines [ 143 , 144 ], Origanum majorana leaf extract in HT-29 cells [ 171 ], and for Scutellaria barbata whole plant extract in HT-29 cells [ 179 ]. Another key molecule that plays a crucial role in the negative regulation of apoptosis is Her2, belonging to the human epidermal growth factor receptor family.…”

Protective Effect of <i>Lepedium sativum</i> against 2, 4-Dichlorophenoxyacetic Acid Hepatotoxicity: An Electron Microscopic Study

“…Recent studies such as [1] focused on the Echinacea purpurea that is a medicinal plant used against a variety of treatments, such as wound infections, snake bites in addition to its antioxidant, antitumor and anti-inflammatory properties. Moreover, [2] proved that Micromeria fruticosa Induces Cell Cycle Arrest and Apoptosis in Breast and Colorectal Cancer Cells. Lepidium sativum (LS), known as "Hab al Rashad", is one of the medicinal plants that grow in Saudi Arabia in several areas, such as the Eastern Province and Al-Qassim [3].…”