Induction of apoptosis and inhibition of PI3K/Akt pathway in PC-3 and LNCaP prostate cancer cells by ethanolic neem leaf extract

Gunadharini, Dharmalingam Nandagopal; Elumalai, Perumal; Ramachandran, A.; Kalimuthu, S; Arunakaran, J.

doi:10.1016/j.jep.2011.01.015

Cited by 43 publications

(34 citation statements)

References 36 publications

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“…It was observed that untreated MCF-7 and HeLa cells showed a high expression of cyclin D1, which was significantly downregulated in a time-dependent manner in ENLE-treated cells (Figures 5(a) and 5(b)). These results are consistent with previous studies in which the antiproliferative action of neem and its bioactive components was associated with the downregulation of cyclin D1 expression in cancer cells [15, 16, 37]. …”

Section: Discussionsupporting

confidence: 93%

“…Treatment of these cells at their respective EC 50 concentrations for 48 and 72 h (MCF-7) and 24 and 48 h (HeLa) correspondingly resulted in increased proportion of cells in the sub-G 0 phase of the cell cycle in a time-dependent manner compared to the untreated cells (Figure 4). These results conclusively prove that ENLE induces cell death in these cells mediated by the apoptotic pathway which are in agreement with previous studies that demonstrated apoptosis induction through various mechanisms such as inhibiting PI3 K/Akt pathway, decrease in Bcl-2/Bax ratio with increased expression of Apaf-1 and caspase-3, and cleavage of poly (ADP-ribose) polymerase was the mode of cell death induced by neem or its derivatives such as nimbolide in various cancers [6, 11, 14–16, 35–37, 42]. Thus, the activation of apoptosis is believed to be a critical therapeutic target for chemoprevention-based therapies.…”

Section: Discussionsupporting

confidence: 91%

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Ethanolic Neem (Azadirachta indica) Leaf Extract Prevents Growth of MCF-7 and HeLa Cells and Potentiates the Therapeutic Index of Cisplatin

Sharma

Vas

Goala

et al. 2014

Journal of Oncology

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The present study was designed to gain insight into the antiproliferative activity of ethanolic neem leaves extract (ENLE) alone or in combination with cisplatin by cell viability assay on human breast (MCF-7) and cervical (HeLa) cancer cells. Nuclear morphological examination and cell cycle analysis were performed to determine the mode of cell death. Further, to identify its molecular targets, the expression of genes involved in apoptosis, cell cycle progression, and drug metabolism was analyzed by RT-PCR. Treatment of MCF-7, HeLa, and normal cells with ENLE differentially suppressed the growth of cancer cells in a dose- and time-dependent manner through apoptosis. Additionally, lower dose combinations of ENLE with cisplatin resulted in synergistic growth inhibition of these cells compared to the individual drugs (combination index <1). ENLE significantly modulated the expression of bax, cyclin D1, and cytochrome P450 monooxygenases (CYP 1A1 and CYP 1A2) in a time-dependent manner in these cells. Conclusively, these results emphasize the chemopreventive ability of neem alone or in combination with chemotherapeutic treatment to reduce the cytotoxic effects on normal cells, while potentiating their efficacy at lower doses. Thus, neem may be a prospective therapeutic agent to combat gynecological cancers.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Ethanolic Neem (Azadirachta indica) Leaf Extract Prevents Growth of MCF-7 and HeLa Cells and Potentiates the Therapeutic Index of Cisplatin

Sharma

Vas

Goala

et al. 2014

Journal of Oncology

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“…23 Thus, exploration of new chemicals for treatment of androgen-sensitive and androgeninsensitive prostate cancer is necessary. In the present study, LNCaP and PC-3 cells have been used to study the effects of torulene on the androgen-sensitive and androgen-insensitive human prostate cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Anti-cancer effects of torulene, isolated from Sporidiobolus pararoseus, on human prostate cancer LNCaP and PC-3 cells via a mitochondrial signal pathway and the down-regulation of AR expression

Guo

Cheng

et al. 2017

RSC Adv.

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In this work, we investigated the anti-cancer effect of torulene, a carotenoid from Sporidiobolus pararoseus, on androgen-sensitive/insensitive prostate cancer cells lines and found that torulene induced apoptosis at moderate cytotoxic concentrations in both cell lines. It was further demonstrated that the apoptosis induced by torulene was due to the modulation of Bcl-2 family members, resulting in decrease of mitochondria membrane potential and increase of the intracellular calcium concentration. Furthermore, its growth-inhibitory effects on LNCaP cells also showed a relationship with the down-regulation of AR and PSA expression. Therefore, the results indicated that a mitochondria-mediated pathway and the expression of AR might play essential roles in the apoptosis process induced by torulene in prostate cancer cells.

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“…One of the bioactive fractions of neem leaf (nimbolide) has anti-cancer property (Harish Kumar et al 2010). The apoptosis inducing ability of NLE has been investigated in cancer cells (Dharmalingam et al 2011). The NLE induces cytoplasmic granulation and deteriorates oocyte quality suggesting its potential use for female fertility regulation in brown dog ticks (Denardi et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals

et al. 2014

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Neem (Azadirachta indica L.) leaf has been widely used in ayurvedic system of medicine for fertility regulation for a long time. The molecular mechanism by which neem leaf regulates female fertility remains poorly understood. Animal studies suggest that aqueous neem leaf extract (NLE) induces reactive oxygen species (ROS) - mediated granulosa cell apoptosis. Granulosa cell apoptosis deprives oocytes from nutrients, survival factors and cell cycle proteins required for the achievement of meiotic competency of follicular oocytes prior to ovulation. Under this situation, follicular oocyte becomes more susceptible towards apoptosis after ovulation. The increased level of hydrogen peroxide (H2O2) inside the follicular fluid results in the transfer of H2O2 from follicular fluid to the oocyte. The increased level of H2O2 induces p53 activation and over expression of Bax protein that modulates mitochondrial membrane potential and trigger cytochrome c release. The increased cytosolic cytochrome c level induces caspase-9 and caspase-3 activities that trigger destruction of structural and specific proteins leading to DNA fragmentation and thereby oocyte apoptosis. Based on these animal studies, we propose that NLE induces generation of ROS and mitochondria-mediated apoptosis both in granulosa cells as well as in follicular oocyte. The induction of apoptosis deteriorates oocyte quality and thereby limits reproductive outcome in mammals.

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Induction of apoptosis and inhibition of PI3K/Akt pathway in PC-3 and LNCaP prostate cancer cells by ethanolic neem leaf extract

Cited by 43 publications

References 36 publications

Ethanolic Neem (Azadirachta indica) Leaf Extract Prevents Growth of MCF-7 and HeLa Cells and Potentiates the Therapeutic Index of Cisplatin

Ethanolic Neem (Azadirachta indica) Leaf Extract Prevents Growth of MCF-7 and HeLa Cells and Potentiates the Therapeutic Index of Cisplatin

Anti-cancer effects of torulene, isolated from Sporidiobolus pararoseus, on human prostate cancer LNCaP and PC-3 cells via a mitochondrial signal pathway and the down-regulation of AR expression

Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals

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