Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase‐Dependent and p53‐Independent Pathway in Breast Cancer Cell Lines

Abstract

Breast cancer is the second leading cause of cancer death among women and despite significant advances in therapy, it remains a critical health problem worldwide. Allium atroviolaceum is an herbaceous plant, with limited information about the therapeutic capability. We aimed to study the anticancer effect of flower extract and the mechanisms of action in MCF-7 and MDA-MB-231. The extract inhibits the proliferation of the cells in a time- and dose-dependent manner. The underlying mechanism involved the stimulation of S and G2/M phase arrest in MCF-7 and S phase arrest in MDA-MB-231 associated with decreased level of Cdk1, in a p53-independent pathway. Furthermore, the extract induces apoptosis in both cell lines, as indicated by the percentage of sub-G0 population, the morphological changes observed by phase contrast and fluorescent microscopy, and increase in Annexin-V-positive cells. The apoptosis induction was related to downregulation of Bcl-2 and also likely to be caspase-dependent. Moreover, the combination of the extract and tamoxifen exhibits synergistic effect, suggesting that it can complement current chemotherapy. LC-MS analysis displayed 17 major compounds in the extract which might be responsible for the observed effects. Overall, this study demonstrates the potential applications of Allium atroviolaceum extract as an anticancer drug for breast cancer treatment.

A Detailed Chemical and Biological Investigation of Twelve Allium Species from Eastern Anatolia with Chemometric Studies

“…In general, there are some studies on the cytotoxic activity of Allium species in the literature [11–14] . However, the studied 12 Allium species were tested against DLD‐1 cancerous cell lines for the first time in this study.…”

“…A. atroviolaceum , commonly named broadleaf wild leek, is mostly used as a food additive, a source of vitamins, and in the treatment of arthritis and rheumatism [10] . Nevertheless, the valuable properties of this species have not been studied sufficiently [11–14] …”

“…Besides, there are cytotoxic activity studies only on A. atroviolaceum against PC3 (prostate), HeLa (cervical), HepG2 (liver), MCF‐7 (breast), and MDA‐MB‐231 (breast) cancerous cell lines [11–14,21] together with apoptosis assays. Up to date, some classes of compounds, such as flavones, [22] sulfurous compounds, [30] steroids, [10] saponins [31] have been isolated and elucidated from Allium species.…”

Lauryl Gallate Induces Apoptotic Cell Death through Caspase-dependent Pathway in U87 Human Glioblastoma CellsIn Vitro

“…It is well known that cancer cell apoptosis can be induced through caspase-dependent and -independent pathways (33,34). Thus, in order to investigate whether LG induced apoptosis in U87 cells via the activation of caspases, the enzymatic activities of caspases -2, -3, -8, -9 and 12 were measured.…”

Antiproliferative Effect of Ornithogalum balansae on Human Cancer Cell Lines

“…These are compatible with the MTT results and showed that MeOH flower extracts prevented migration of A549 cells. It has been reported that plant extracts cause antiproliferation by using the apoptotic or necrotic pathways [28][29][30] . This study investigated whether O. balansae flower/bulb extracts exhibit an inhibitory effect on A549 cells using the apoptotic pathway by employing DNA fragmentation and caspase-3 measurements.…”