All results are expressed in the histogram as total percentages of cells from four different groups with mean SD of three independent determinations

All results are expressed in the histogram as total percentages of cells from four different groups with mean SD of three independent determinations. effect on cell migration. Assessment of probable genetic toxicity by these extracts revealed no or minimum incidence of genetic toxicity. Therefore, the studied plant extracts are exhibiting potent anticancer activity based upon marked induction of tumor-cell death. (XA) which is a member of the family Annonaceae, is used as a spice in Western and Central Africa, as well as to treat bronchitis, headache and ulceration [5]. In addition to its anti-diabetic effect [6], anti-anaphylactic and anti-inflammatory LEQ506 activities [7], several studies have shown that XA extracts possess antibacterial and FTDCR1B antifungal activities [8,9,10,11]. (IC) (family Poaceae) also known as spear grass in West Africa, has diuretic, anti- inflammatory and antibacterial activities [12,13]. It also shows a potent anthelmintic activity [14] and the methanolic extract of its rhizomes was reported as a significant neuroprotective against glutamate-induced neurotoxicity in primary cultures of rat cortical cells [15]. (EG), (family Compositae) is traditionally used as a medicinal agent mainly in Africa and Asia. It is mainly used as heart and gastric troubles LEQ506 spice, reducing as well asthma attacks. In previous studies, the root methanolic extract showed significant antioxidant [16], antibacterial [17], and antifungal effects [18]. The methanolic extract of EG roots also exhibited a significant activity against M. tuberculosis [19], the methanolic extract from the underground part also reported for cytotoxic activity against prostate cancer (Mia PaCa2) and two leukemia cells (CCRF-CEM and CEM/ADR5000) [20]. (DP), (family Moraceae) is widely used in traditional medicine and represents a great source of active constituents including flavonoids, alkaloids and phenolic compounds [21,22,23]. It has a therapeutic LEQ506 effect on cardiovascular disorders, snakebites, headache and stomach disorders, moreover it exhibits a potent antimicrobial activity and as its methanolic showed antibacterial activity against a panel of Gram-negative bacteria including multidrug resistant (MDR) phenotypes [13]. Recent study reported the isolation of two isoprenylated flavones from the root extract of DP that activate AMP-activated protein kinase (AMPK), stimulate glucose uptake and lower glycemia [24]. Recently, various studies were conducted for screening the cytotoxic activity of these plant extracts against a variety of cancer types and resistance. These studies have shown a promising effect of using these extracts against some cancer cell lines [25,26,27,28,29]. Despite the useful biological activity expressed by certain plants, the study of their possible toxicity remains particularly important. As some chemicals or secondary metabolites from plants are toxins like substances that may cause harmful effects to humans. In this study, a well-established evaluation of the anticancer potential of these four plant extracts: (i) XA, (ii) IC, (iii) EG and (iv) DP was performed to assess their activities in the inhibition of cell proliferation in seven different human cancer cell lines: HeLa (cervical), MDA-MB-231 (breast), A549 (lung), HepG2 (liver), U-87 (glioblastoma, brain), SK-OV-3 (ovarian) and HL60 (leukemia). As well, an assessment of in vitro toxicity of these plant extracts was performed in non-cancerous HEK-293 cells. HeLa cells showed a higher sensitivity in cell proliferation assay upon treatment with these extracts, so further studies of the alteration and induction of cell death were investigated in HeLa cell line, by comparing the treated cells with these extracts to the untreated cells, using different assays involving cell cycle analysis, the caspase 3/7 activity and mitochondrial membrane potential (MMP). The effect of the studied medicinal plants on the inhibition of cell progression and metastasis was assessed using the wound healing assay. Furthermore, a single cell gel electrophoresis assay was performed to exclude any probable genetic toxicity upon using of these extracts in cancer treatment. 2. Results and Discussion 2.1. Cell Proliferation Assay The anti-proliferation effect is the first indication to be assessed when investigation novel antitumor agents, thus the cell growth inhibitory activity of the four plant extracts was initially assessed on the HeLa (cervical cancer) cell line 48 h after treatment with different concentrations of the crude methanol extracts. A dose dependent decrease in cell viability was observed (Figure 1). At a concentration of 50 g/mL of each crude extract, DP and EG inhibited the cell growth by more than 99%, followed by XA with 90% and IC with 80%. The comparative IC50 values of XA, IC, EG and DP for HeLa cells were shown in (Figure 1E). The most potent anti-proliferative effect was induced by DP with IC50 value of 19.35 g/mL, followed by XA with IC50 value of 24.94 g/mL. EG and IC showed a quite similar inhibitory effect on cell growth with IC50.