Induction of apoptotic cell death by Pharbitis nil extract in HER2-overexpressing MCF-7 cells

Aim of the study

We performed this study to investigate the anti-cancer activity of Pharbitis nil (PN) ethanol extract which has been used for herbal medicinal treatment against diseases in East Asia.

Materials and methods

We analyzed the effects of PN extract on proliferation of breast cancer cell lines, MCF-7 control vector (vec) and MCF-7 human epidermal growth factor receptor 2 (HER2) cells engineered to overexpress oncogenic HER2 via retroviral infection. We performed the proliferation assay to measure the growth rate of the cells. FACS analysis was used to analyze the cell cycle. Western blot analysis was used to investigate the effect of PN on the level and activation of intracellular molecules.

Results

We found that PN extract inhibited the proliferation of both MCF-7 vec and MCF-7 HER2 cells. This growth inhibition was accompanied with the increase of sub G0/G1 apoptotic fractions. When we check the efficiency of PN on the level of intracellular signaling molecules, we found that PN extract induced the inhibition of phosphorylation of HER2 and its downstream effectors, Akt and extracellular signal-regulated kinases (ERK). Active forms of both Akt and ERK were gradually decreased in PN-treated MCF-7 vec and MCF-7 HER2 cells suggesting that the growth suppressive activity of PN is related to signaling pathway. The level of cyclin D also diminished in PN-treated both cells suggesting that PN may inhibit the growth of MCF-7 vec and MCF-7 HER2 cells by perturbing cell cycle progression. It should be noted that PN decreased the growth rate of both MCF-7 vec and MCF-7 HER2 cells without changing the level and activation of p53.

Conclusion

PN extract suppressed the proliferation rate of HER-2 overexpressing MCF-7 breast cancer cells inducing apoptotic cell death in vitro. Our data demonstrates that PN extracts contain useful anti-tumor activity especially against HER2 overexpressing breast cancer.     

Selective Inhibition of Cell Proliferation by Lycopene in MCF‐7 Breast Cancer Cells In vitro: A Proteomic Analysis

Lycopene, a red pigmented carotenoid present in many fruits and vegetables such as tomatoes, has been associated with the reduced risk of breast cancer. This study sought to identify proteins modulated by lycopene during cell proliferation of the breast cancer cell line MCF‐7 to gain an understanding into its mechanism of action. MCF‐7 breast cancer cells and MCF‐10 normal breast cells were treated with 0, 2, 4, 6, 8, and 10 μM of lycopene for 72 h. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) tetrazolium reduction assay was used to measure cell proliferation and two‐dimensional fluorescence difference gel electrophoresis to assess the changes in protein expression, which were identified using MALDI‐ToF/ToF (matrix‐assisted laser desorption ionization tandem time‐of‐flight) and Mascot database search. MTT and cell proliferation assays showed that lycopene selectively inhibited the growth of MCF‐7 but not MCF‐10 cells. Difference gel electrophoresis analysis revealed that proteins in the MCF‐7 cells respond differently to lycopene compared with the MCF‐10 cells. Lycopene altered the expression levels of proteins such as Cytokeratin 8/18 (CK8/18), CK19 and their post translational status. We have shown that lycopene inhibits cell proliferation in MCF‐7 human breast cancer cells but not in the MCF‐10 mammary epithelial cells. Lycopene was shown to modulate cell cycle proteins such as beta tubulin, CK8/18, CK19 and heat shock proteins. Copyright © 2012 John Wiley & Sons, Ltd.     

Cytotoxic Impact of Costunolide Isolated from Costus speciosus on Breast Cancer via Differential Regulation of Cell Cycle—An In‐vitro and In‐silico Approach

Costunolide, a sesquiterpene lactone, is a biologically active molecule found in most of the medicinally valuable plants. The present study aims to evaluate the anticancer property of costunolide isolated from Costus speciosus against breast cancer cell lines (MCF‐7 and MDA‐MB‐231). Costunolide effectively reduced the viability of both MCF‐7 and MDA‐MB‐231 cell lines at an IC₅₀ value of 40 μM. Flow cytometric analysis revealed costunolide mediated cell cycle arrest at G2/M phase in both the cell types. Western blotting results confirmed the alterations in the expression of cell cycle regulators (cyclin D1, D3, CDK‐4, CDK‐6, p18 INK4c, p21 CIP1/Waf‐1 and p27 KIP1) and apoptosis inducers (caspase‐3 and caspase‐9) upon costunolide treatment in comparison with their expressions in normal breast cell line (MCF‐10A). Costunolide mediated downregulation of positive cell cycle regulators and upregulation of negative cell cycle regulators were related to the induction of apoptosis in cancer cells. The above results were validated with in‐silico results that predicted stable interactions between costunolide and cancer targets. Thus costunolide effectively induced breast cancer cell apoptosis targeting cell cycle regulation, and the compound can be used as an effective herbal therapeutic molecule to treat breast cancer with further explorations. Copyright © 2015 John Wiley & Sons, Ltd.     

贝母素甲抑制人乳腺癌细胞MCF-7/TAM增殖及其对细胞凋亡的影响

目的:探讨贝母素甲抑制耐三苯氧胺人乳腺癌细胞MCF-7/TAM的增殖及其机制。方法:采用四甲基偶氮唑蓝(MTT)比色分析法检测贝母素甲作用于MCF-7/TAM细胞后的抑制率;用流式细胞术检测细胞周期和凋亡率;用免疫细胞化学法检测Bcl-2表达变化。结果:贝母素甲对MCF-7/TAM细胞有明显的抑制作用,呈浓度和时间依赖性。作用48h后能诱导细胞凋亡,细胞周期被阻滞于G1期(P0.05)。免疫细胞化学法检测Bcl-2表达减弱(P0.01)。结论:贝母素甲可抑制MCF-7/TAM细胞的增殖,并诱导其凋亡。     

Pachastrissamine from Pachastrissa sp. Inhibits Melanoma Cell Growth by Dual Inhibition of Cdk2 and ERK‐mediated FOXO3 Downregulation

Melanoma cells are relatively resistant to apoptosis compared with other tumor cell types, and thus, chemotherapy, radiotherapy and immunotherapy are not effective in treating melanoma. Pachastrissamine (PA) exhibits cytotoxic activity and promotes apoptosis in several cancer cells. However, its specific molecular mechanisms have not been characterized fully. This study investigated the antimelanoma effect of PA, an anhydrophytosphingosine derived from marine sponge, and its underlying molecular mechanisms. The data demonstrated that treatment with PA inhibited the phosphorylation of ERK and subsequent ERK‐mediated FOXO3 phosphorylation in melanoma cells. Interestingly, PA did not inhibit AKT‐mediated FOXO3 phosphorylation. Therefore, it appears that PA‐induced apoptosis results from the inhibition of ERK. Furthermore, intravenous administration of PA was found to suppress melanoma cell growth in a C57BL6 mouse without causing side effects. Additionally, PA inhibited the production of Cdk2, which is involved in cell cycle regulation. Taken together, inhibition of melanoma cell growth by PA is a result of the inhibition of ERK‐mediated FOXO3 downregulation and decreased Cdk2 levels. The results of this study imply that dual inhibition of the ERK pathway and cell cycle progression could be an effective approach to control the growth of melanoma cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Rutin,a Quercetin Glycoside,Restores Chemosensitivity in Human Breast Cancer Cells

Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate‐binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3‐O‐β‐d ‐rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB‐MDA‐231, selected as representative for triple‐negative breast cancer and (ii) MCF‐7 used as a well‐characterized model of HER2‐negative breast cancer. To assess the cytocompatibility of rutin against non‐cancer cells, primary human mammary fibroblasts were used as control and non‐target cells. In MDA‐MB‐231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p < 0.05) increased the anticancer activity of both chemotherapeutics, at 24–48–72 h, and decreased the activity of the adenosine triphosphate‐binding cassette transporters, namely, P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 μM and 50 μM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non‐selective inhibition of P‐gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple‐negative breast cancer cells, successfully arresting cell cycle progression. Copyright © 2017 John Wiley & Sons, Ltd.     

加味四君子汤含药血清对肝癌Hep-G2细胞的影响

目的:探讨加味四君子汤含药血清对肝癌Hep-G2细胞增殖、凋亡、周期的影响及其作用机制。方法:不同浓度加味四君子汤含药血清处理Hep-G2细胞后,采用细胞活性检测试剂盒(CCK-8)检测细胞增殖;Annexin V/碘化丙啶(PI)流式细胞术检测细胞凋亡率和周期;hoechst33342荧光染色观察细胞凋亡形态;免疫印迹法(Western blot)检测细胞中磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/雷帕霉素靶蛋白(m TOR)信号通路相关蛋白表达水平。结果:加味四君子汤含药血清呈浓度依赖性抑制肝癌Hep-G2细胞的增殖,诱导Hep-G2细胞凋亡,阻滞细胞于G0/G1期。hoechst33342染色后,随着含药血清浓度的增加,Hep-G2细胞核显著呈碎块状致密浓染。同时,加味四君子汤含药血清能够抑制Hep-G2细胞Akt,m TOR,核糖体S6蛋白激酶(S6),真核翻译起始因子4E结合蛋白1(4EBP1)的磷酸化,从而上调Bcl-2相关X蛋白(Bax)和下调细胞周期蛋白(Cyclin D1),B淋巴细胞瘤-2(Bcl-2)的表达。加味四君子汤含药血清与300 nmol·L-1的PI3K/m TOR双重抑制剂VS-5584联合使用具有协同作用,含药血清能增强PI3K/m TOR双重抑制剂VS-5584对Hep-G2细胞中PI3K/Akt/m TOR信号通路靶点Akt和m TOR磷酸化的抑制作用。结论:加味四君子汤含药血清能抑制Hep-G2细胞的增殖,诱导其凋亡,阻滞其于G0/G1期,其机制可能通过阻断PI3K/Akt/m TOR信号通路而实现。     

紫甘蓝提取液对人乳腺癌细胞生长和迁移的抑制作用

目的:探讨紫甘蓝提取物对乳腺癌细胞MCF7生长和迁移的抑制作用。方法:应用MTT法检测不同浓度紫甘蓝提取物对MCF7增殖的抑制作用,并用倒置相差显微镜观察细胞形态,Annexin V-FITC/PI染色细胞后用流式细胞术检测不同浓度紫甘蓝提取物对MCF7凋亡的影响,采用Transwell法检测不同浓度紫甘蓝提取物对MCF7迁移的影响。采用SPSS16.0软件对实验结果进行统计学处理。结果:紫甘蓝提取物可抑制MCF7的增殖,并呈浓度依赖性和时间依赖性(P0.05),也使MCF7形态发生了异常变化,紫甘蓝提取物可诱导MCF7凋亡、抑制其迁移,且呈浓度-效应关系(P0.05)。结论:紫甘蓝提取物可抑制乳腺癌细胞MCF7生长和迁移。     

Diosmetin exhibits anti‐proliferative and anti‐inflammatory effects on TNF‐α‐stimulated human rheumatoid arthritis fibroblast‐like synoviocytes through regulating the Akt and NF‐κB signaling pathways

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation and proliferation of synovial tissues. Diosmetin is a bioflavonoid possessing an anti‐inflammatory property. Herein, we aimed to study the effects of diosmetin on the inflammation and proliferation of RA fibroblast‐like synoviocytes MH7A cells. MH7A cell proliferation was measured using cell counting kit‐8 assay. Cell apoptosis was examined using flow cytometry. The production of inflammatory cytokines including interleukin (IL)‐1β, IL‐6, IL‐8, and matrix metalloproteinase‐1 (MMP‐1) was measured using enzyme‐linked immunosorbent assay (ELISA). Results showed that diosmetin inhibited tumor necrosis factor‐α (TNF‐α)‐induced proliferation increase in MH7A cells in a dose‐dependent manner. Diosmetin treatment resulted in an increase in apoptotic rates and a reduction in TNF‐α‐induced production of IL‐1β, IL‐6, IL‐8, and MMP‐1 in MH7A cells. Furthermore, diosmetin inhibited TNF‐α‐induced activation of protein kinase B (Akt) and nuclear factor‐κB (NF‐κB) pathways in MH7A cells. Suppression of Akt or NF‐κB promoted apoptosis and inhibited TNF‐α‐induced proliferation increase and production of IL‐1β, IL‐6, IL‐8, and MMP‐1 in MH7A cells, and diosmetin treatment enhanced these effects. Taken together, these findings suggested that diosmetin exhibited anti‐proliferative and anti‐inflammatory effects via inhibiting the Akt and NF‐κB pathways in MH7A cells.     

F1012‐2 inhibits the growth of triple negative breast cancer through induction of cell cycle arrest,apoptosis, and autophagy

Sesquiterpene lactones (SLs) are plant‐derived constituents that have been proved to have potential antitumour activity. However, the intracellular molecular targets of SLs and the underlying molecular mechanisms have not been well elucidated. Here, we report that F1012‐2, a novel SL active fraction, isolated from Eupatorium lindleyanum DC., can significantly inhibit the growth of triple‐negative breast cancer (TNBC) cells (MDA‐MB‐231 and MDA‐MB‐468) but has no obvious inhibitory effect on the growth of human mammary epithelial cells (MCF‐10A). The related mechanisms on cell growth inhibition of F1012‐2 were demonstrated by inducing apoptosis in a caspase‐dependent manner through the intrinsic pathway and extrinsic pathway. F1012‐2 could also activate autophagy in TNBC cells. Simultaneously, we found that F1012‐2‐induced apoptosis was enhanced by inhibition of autophagy. Furthermore, F1012‐2 could induce cell cycle arrest at G2/M phase with decreasing expression of cyclin B1, cdc2, and upregulating p21, p‐cdc2. Also, F1012‐2 activated Akt and p38 signalling pathways. In vivo, F1012‐2 exhibited a potential antitumour effect in MDA‐MB‐231 xenografts without apparent toxicity. Taken together, our results identified that F1012‐2 inhibited cell growth via multiple signalling pathways in vitro and in vivo. These data suggest that F1012‐2 may be a potential natural active fraction for the treatment of TNBC.     

Fangchinoline Induces G1 Arrest in Breast Cancer Cells Through Cell‐Cycle Regulation

Fangchinoline, an alkaloid derived from the dry roots of Stephaniae tetrandrine S. Moore (Menispermaceae), has been shown to possess cytotoxic, anti‐inflammatory, and antioxidant properties. In this study, we used Fangchinoline to inhibit breast cancer cell proliferation and to investigate its underlying molecular mechanisms. Human breast cancer cell lines, MCF‐7 and MDA‐MB‐231, were both used in this study. We found that Fangchinoline significantly decreased cell proliferation in a dose‐dependent manner and induced G1‐phase arrest in both cell lines. In addition, upon analysis of expression of cell cycle‐related proteins, we found that Fangchinoline reduced expression of cyclin D1, cyclin D3, and cyclin E, and increased expression of the cyclin‐dependent kinase (CDK) inhibitors, p21/WAF1, and p27/KIP1. Moreover, Fangchinoline also inhibited the kinase activities of CDK2, CDK4, and CDK6. These results suggest that Fangchinoline can inhibit human breast cancer cell proliferation and thus may have potential applications in cancer therapy. Copyright © 2013 John Wiley & Sons, Ltd.     

Steroidal Glycosides with Antiproliferative Activities from Digitalis trojana

The phytochemical investigation of Digitalis trojana led to the isolation of two cardiac glycosides (1, 2), one pregnane glycoside (3), three furostanol type saponins (4–6), along with three cleroindicins (7–9), four phenylethanoid glycosides (10–13), two flavonoids (14, 15) and two phenolic acid derivatives (16, 17). The structure elucidation of the isolates was carried out by NMR experiments as well as ESI‐MS. The cytotoxic activity of compounds 1–13 against a small panel of cancer cell lines, namely MCF‐7, T98G, HT‐29, PC‐3, A375 and SH‐SY5Y, was investigated. Compounds 1–6 showed antiproliferative activity against human breast MCF‐7 and colon HT‐29 cancer cell lines with IC₅₀ values ranging from 8.3 to 50 μM. In order to understand the mechanism involved in the cell death, the active compounds were tested as pro‐apoptotic agents using propidium iodide staining by flow cytometry method. No significant increase was observed in the apoptosis of the MCF‐7 and HT‐29 cancer cells. Moreover, the effects of the active compounds on cell proliferation were assessed on the same cancer cell lines by cell cycle analysis of DNA content using flow cytometry. No significative changes were observed in the cell cycle of MCF‐7, while significant changes in G₂/M cell cycle phase of HT‐29 cells were observed after treatment with digitalin (1), cariensoside (3) and 22‐O‐methylparvispinoside B (6) at 10 μM. Copyright © 2013 John Wiley & Sons, Ltd.     

Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco‐2 Human Colon Carcinoma Cell Line Through a Selective PPAR‐α‐Dependent Inhibition of Akt/mTOR Pathway

Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve intestinal inflammation. We aimed at evaluating its antiproliferative and antiangiogenic effects in human colon adenocarcinoma Caco‐2 cell line. Caco‐2 cells were treated with increasing concentrations of PEA (0.001, 0.01 and 0.1 μM) in the presence of peroxisome proliferator‐activated receptor‐a (PPAR‐α) or PPAR‐γ antagonists. Cell proliferation was evaluated by performing a MTT assay. Vascular endothelial growth factor (VEGF) release was estimated by ELISA, while the expression of VEGF receptor and the activation of the Akt/mammalian target of rapamycin (mTOR) pathway were evaluated by western blot analysis. PEA caused a significant and concentration‐dependent decrease of Caco‐2 cell proliferation at 48 h. PEA administration significantly reduced in a concentration‐dependent manner VEGF secretion and VEGF receptor expression. Inhibition of Akt phosphorylation and a downstream decrease of phospho‐mTOR and of p‐p70S6K were observed as compared with untreated cells. PPAR‐α, but not PPAR‐γ antagonist, reverted all effects of PEA. PEA is able to decrease cell proliferation and angiogenesis. The antiangiogenic effect of PEA depends on the specific inhibition of the AkT/mTOR axis, through the activation of PPAR‐α pathway. If supported by in vivo models, our data pave the way to PEA co‐administration to the current chemotherapeutic regimens for colon carcinoma. Copyright © 2016 John Wiley & Sons, Ltd.     

In Vitro culture studies of FlorEssence on human tumor cell lines

FlorEssence (FE) is an herbal tea widely used by patients to treat chronic conditions in North America, particularly cancer patients during chemo- and radiation therapy. Although individual components of FE have antioxidant, antiestrogenic, immunostimulant and antitumor properties, in vitro evidence of anticancer activity for the herbal tea itself is still lacking. We studied the antiproliferative effect of FE on MCF7 and MDA-MB-468 human breast cancer, and Jurkat and K562 leukemia cell lines. We found that FE significantly inhibited the proliferation of both breast and leukemia cells in vitro only at high concentrations, with 50% inhibition of MDA-MB-468 cells at about 1[sol ]20 dilution, Jurkat cells at about 1[sol ]10 dilution and MCF7 and K562 cells at less than 1[sol ]10 dilution. Flow cytometry analysis showed that treatment with a high concentration of FE induced G2[sol ]M arrest in MCF7 and Jurkat cells, with also an increased SubG0[sol ]G1 fraction in MCF7 cells. MDA-MB-468 cells showed a significantly increased Sub G0[sol ]G1 fraction after treatment with 1[sol ]10 dilution of FE while the cell cycle of K562 was unaffected. When MCF7 and MDA-MB-468 breast cancer cells were treated with a combination of FE with either paclitaxel or cisplatin, results showed that only the combination of 1[sol ]20 dilution of FE with 0.5 microM cisplatin resulted in a small but significantly higher MCF7 cell survival than 0.5 microM cisplatin treatment alone. FE at 1[sol ]20 and 1[sol ]50 dilutions did not affect the antiproliferative properties of these two commonly used chemotherapeutic agents. The results suggest that FE at high concentrations show differential inhibitory effect on different human cancer cell lines. Further studies are needed to assess the biological activities of FE.     

Kaempferitrin inhibits proliferation,induces apoptosis,and ameliorates inflammation in human rheumatoid arthritis fibroblast‐like synoviocytes

Rheumatoid arthritis (RA) is a complex chronic inflammatory disease that is associated with the aberrant activation of fibroblast‐like synoviocytes (FLS). Kaempferitrin is a natural flavonoid glycoside that possesses anti‐inflammatory bioactivity. However, the effect of kaempferitrin on RA has not yet been revealed. The aim of the present study was to investigate the effect of kaempferitrin on human RA‐FLS MH7A cell line. We found that kaempferitrin inhibited proliferation and induced apoptosis of MH7A cells. Kaempferitrin decreased the levels of interleukin (IL)‐1β, IL‐6, tumor necrosis factor (TNF)‐α, matrix metalloproteinase (MMP)‐1, and MMP‐3 in MH7A cells. Moreover, kaempferitrin blocked the activation of nuclear factor‐κB (NF‐κB) and protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathways. Furthermore, treatment with kaempferitrin decreased paw thickness and arthritis scores, and reduced the serum levels of IL‐1β, IL‐6, and TNF‐α in a collagen‐induced arthritis mouse model. In conclusion, kaempferitrin inhibited cell proliferation, induced cell apoptosis, and ameliorated inflammation of RA‐FLS by suppressing the NF‐κB and Akt/mTOR pathways.     

Improving anticancer activities of Oplopanax horridus root bark extract by removing water‐soluble components

O. horridus is used as a folk medicine by natives in the Northern Pacific coast of North America. This experiment studied the antiproliferative effects of the extract of O. horridus root bark and its fractions chromatographed from Dianion HP20 resin column with water, 30, 50, 70 and 100% ethanol on human breast cancer MCF‐7 cells and non‐small cell lung cancer (NSCLC) cells. The role of O. horridus in the cell cycle and apoptosis of MCF‐7 cells was also investigated. The results showed that the 70% and 100% ethanol fractions demonstrated more potent antiproliferative effects than the total extract on both cell lines. The antiproliferative effects may result from the enrichment of active constituents detected by high performance liquid chromatography (HPLC). The IC₅₀ of the total extract, 50, 70, and 100% ethanol fractions for antiproliferation on MCF‐7 cells were 248.4, 123.1, 44.0, and 31.5 μg/mL, respectively, and on NSCLC cells were 125.3, 271.1, 17.6, and 23.2 μg/mL, respectively. On the other hand, the water and 30% ethanol fractions significantly promoted cell proliferation on MCF‐7 cells at concentrations > 100 μg/mL, suggesting that the hydrophilic fractions should be removed from the extract when used for cancer chemoprevention in order to achieve desirable activities. The effects of the total extract on cell cycle and apoptosis were similar to that of the 100% ethanol fraction because of the similarity of their chemical composition. At higher concentrations, the apoptotic effects of the 70% ethanol fraction are more significant. Data from this study suggested that the 70% and 100% ethanol fractions are active antiproliferative fractions and that induction of apoptosis is the mechanism involved in the antiproliferative effect observed. Copyright © 2010 John Wiley & Sons, Ltd.     

Apoptotic effect of lambertianic acid through AMPK/FOXM1 signaling in MDA‐MB231 breast cancer cells

Though lambertianic acid (LA) was known to exert antitumor effect in liver and prostate cancers, its underlying anticancer mechanism is never reported in breast cancers so far. Thus, in this study, apoptotic mechanism of LA was elucidated in MDA‐MB‐231 breast cancer cells. Here, LA increased cytotoxicity in MCF‐7 and MDA‐MB‐231 cells; enhanced sub‐G1 population, G2/M arrest, and cleaved poly(ADP‐ribose) polymerase; activated phosphorylation of AMP‐activated protein kinase (AMPK)/acetyl‐CoA carboxylase pathway; and also suppressed phosphorylation of AKT and the expression of forkhead box M1 (FOXM1), X‐linked inhibitor of apoptosis protein, B‐cell lymphoma 2, and CyclinB1 in MDA‐MB‐231 cells. Furthermore, AMPK inhibitor compound C reversed the effect of LA on FOXM1, Cyclin B1, and cleaved poly(ADP‐ribose) polymerase in MDA‐MB‐231 cells. Notably, immunoprecipitation revealed that LA disturbed the direct binding of AKT and FOXM1 in MDA‐MB‐231 cells. Overall, these findings suggest that LA‐induced apoptosis is mediated via activation of AMPK and inhibition of AKT/FOXM1 signaling pathway.