Ethanolic neem (Azadirachta indica A. Juss) leaf extract induces apoptosis and inhibits the IGF signaling pathway in breast cancer cell lines

Elumalai, Perumal; Gunadharini, Dharmalingam Nandagopal; Kalimuthu, S; Banudevi, Sivanantham; Arunkumar, Ramesh; Selvanesan, Benson Chellakkan; Sharmila, Govindaraj; Arunakaran, J.

doi:10.1016/j.bionut.2011.12.008

Cited by 30 publications

(18 citation statements)

References 39 publications

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“…As Bax can activate Caspase and induce mitochondria1 dysfunction, the expression of Bcl-2 blocks both events (Tathagata et al, 2002). Elumalai et al (2012) reported that the up regulation of Bax and down-regulation of Bcl-2 in breast cancer cells. In the present study, the expression of Bcl-2 was found to be decreased and incontrast the Bax expression was increased which in turn could be a sign of induction of apoptosis by the D-pinitol in MCF-7 cells.…”

Section: Resultsmentioning

confidence: 99%

D-Pinitol Promotes Apoptosis in MCF-7 Cells via Induction of p53 and Bax and Inhibition of Bcl-2 and NF-κB

Rengarajan¹,

Nandakumar²,

Rajendran³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Resultsmentioning

confidence: 99%

D-Pinitol Promotes Apoptosis in MCF-7 Cells via Induction of p53 and Bax and Inhibition of Bcl-2 and NF-κB

Rengarajan¹,

Nandakumar²,

Rajendran³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Nimbolide was found to exhibit anticancer activity in a wide variety of tumour cells, including choriocarcinoma, leukaemia and melanoma cells. In our previous study, we observed that nimbolide significantly inhibited cell proliferation with IC50 values of 4.0 and 2.7 μM for 24 and 48 h, respectively, in MCF‐7 cell line and 6.0 and 3.2 μM for 24 and 48 h, respectively, in MDA‐MB‐231 cell line …”

Section: Discussionmentioning

confidence: 91%

“…Our earlier reports demonstrated that ethanolic neem leaf extract (ENLE) induced the apoptosis and inhibited the proliferation of prostate and breast cancer cells . Although ENLE is a mixture of phytochemicals, several studies showed that nimbolide is the major constituent that mediates the anticancer property.…”

Section: Introductionmentioning

confidence: 99%

“…Our earlier reports demonstrated that ethanolic neem leaf extract (ENLE) induced the apoptosis and inhibited the proliferation of prostate and breast cancer cells. 19,20 Although ENLE is a mixture of phytochemicals, several studies showed that nimbolide is the major constituent that mediates the anticancer property. Previous studies from our laboratory reported that nimbolide-induced apoptosis in breast cancer cells by activation of both extrinsic and intrinsic apoptotic pathways.…”

Section: Introductionmentioning

confidence: 99%

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Nimbolide inhibits IGF‐I‐mediated PI3K/Akt and MAPK signalling in human breast cancer cell lines (MCF‐7 and MDA‐MB‐231)

Elumalai

Ramachandran

Selvanesan

et al. 2014

Cell Biochemistry & Function

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The insulin-like growth factor I (IGF-I) signalling pathway contributes a major role on various cancer cell proliferation, survival and cell cycle. The present study was aimed to investigate the effect of nimbolide on IGF signalling and cell cycle arrest in MCF-7 and MDA-MB-231 breast cancer cell lines. The protein expression of IGF signalling molecules and cell cycle protein levels was assessed by western blot analysis. In order to study the interaction of nimbolide on IGF-1 signalling pathway, IGF-I and phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) were used to treat MCF-7 and MDA-MB-231 cells. Further, the cell cycle arrest was analysed by flow cytometry. The protein expression of IGF signalling molecules was significantly decreased in nimbolide-treated breast cancer cells. PI3K inhibitor and IGF-I with nimbolide treatment notably inhibited phosphorylated Akt. The cell cycle arrest was observed at the G0/G1 phase, and accumulation of apoptotic cells was observed in nimbolide-treated breast cancer cell lines. Nimbolide also increased the protein expression of p21 and decreased the cyclins in both the cell lines. Nimbolide decreases the proliferation of breast cancer cells by modulating the IGF signalling molecules, which could be very useful for the breast cancer treatment.

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“…In a recent study conducted on both MCF-7 and MDA MB-231 breast cancer cells revealed that crude extract decreases the expression of various signaling molecules such as RAS, RAF, p-Erk, p-Akt and Cyclin D1 (8,9). Thus active constituents of neem leaf extract can be used as a potent inhibitor of breast cancer progression by virtue of their ability to target various signaling molecules involved in complicating the disease.…”

Section: Ivyspringmentioning

confidence: 99%

Targeting breast cancer cell signaling molecules PI3K and Akt by phytochemicals Cannabidiol, Nimbin and Acetogenin: An in silico approach

Mittal¹,

Chaudhry²,

Mukherjee³

2018

J. Biomed

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The phosphatidylinositol 3-kinase (PI3K)/serine-theronine protein kinase Akt is a vital signaling cascade involved in cell survival, progression and thus causes various types of cancers. Various kinase inhibitors targeting PI3K/Akt have been extensively studied but promising results could not be obtained because of toxicity and resistance issues. The aim of present study was to analyze the interaction of plant derived natural moieties such as nimbin, cannabidiol and acetogenin to PI3K and Akt signaling molecules. Results showed that nimbin, cannabidiol and acetogenin significantly binds to both signaling molecules. They revealed almost equivalent potency of binding to PI3K at their respective active site but nimbin exhibited lower free energy of binding with Akt. A combinational drug therapy comprises of these natural metabolites that can target these specific protein kinases efficiently can prove as a boon for breast and other cancers treatment.

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Ethanolic neem (Azadirachta indica A. Juss) leaf extract induces apoptosis and inhibits the IGF signaling pathway in breast cancer cell lines

Cited by 30 publications

References 39 publications

D-Pinitol Promotes Apoptosis in MCF-7 Cells via Induction of p53 and Bax and Inhibition of Bcl-2 and NF-κB

D-Pinitol Promotes Apoptosis in MCF-7 Cells via Induction of p53 and Bax and Inhibition of Bcl-2 and NF-κB

Nimbolide inhibits IGF‐I‐mediated PI3K/Akt and MAPK signalling in human breast cancer cell lines (MCF‐7 and MDA‐MB‐231)

Targeting breast cancer cell signaling molecules PI3K and Akt by phytochemicals Cannabidiol, Nimbin and Acetogenin: An in silico approach

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