Caspase and mitogen activated protein kinase pathways are involved in Solanum lyratum herba induced apoptosis

Lee, Jin Hyuk; Lee, Yun-Hee; Lee, Hyo‐Jung; Lee, Hyo‐Jeong; Lee, Eun-Ok; Ahn, Kwang Seok; Shim, Bum Sang; Bae, Hyunsu; Choi, Su-Mi; Ahn, Kwang‐Soon; Baek, Nam‐In; Kim, Daekeun; Kim, Sung Hoon

doi:10.1016/j.jep.2009.02.013

Cited by 14 publications

(8 citation statements)

References 12 publications

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“…The extrinsic and intrinsic apoptotic pathways-associated proteins (Figure 6) were changed, which subsequently promoted caspase-8 and caspase-9 activation to activate downstream effectors caspase-3 in SLE-treated WEHI-3 cells. Lee et al reported that hexane fraction of Solanum lyratum herba induced apoptosis through activated caspase-8, -9, and -3 proteins in LLC cells [22]. The previous studies [18–20, 22] supported our suggestions to show that SLE induced apoptosis in WEHI-3 cells through both extrinsic- and intrinsic-dependent signaling pathways.…”

Section: Discussionsupporting

confidence: 86%

“…SLE also triggered apoptosis in human cervical cancer HeLa cells through Fas/Fas ligand (FasL) expression [18] promoted the activity of protein kinase A (PKA) in the gastric cancer cells [19, 20] and provoked caspase-3-mediated apoptosis in human colon cancer colo 205 cells [21]. Additionally, SLE exhibited antitumor activity through caspase-8 and caspase-9 activations and mitogen-activated protein kinase (MAPK) regulation in Lewis lung carcinoma (LLC) cells [22]. The goal of this study hypothesized that whether the antileukemia activity of SLE mediates via its direct cytotoxic effect and explores the molecular mechanisms in WEHI-3 murine leukemia cells.…”

Section: Introductionmentioning

confidence: 99%

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Solanum lyratumExtracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor

Yang

Kuo

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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We investigated the molecular mechanisms of cell cycle arrest and apoptotic death induced bySolanum lyratumextracts (SLE) or diosgenin in WEHI-3 murine leukemia cellsin vitroand antitumor activityin vivo. Diosgenin is one of the components of SLE. Our study showed that SLE and diosgenin decreased the viable WEHI-3 cells and inducedG0/G1phase arrest and apoptosis in concentration- or time-dependent manners. Both reagents increased the levels of ROS production and decreased the mitochondrial membrane potential (ΔΨm). SLE- and diosgenin-triggered apoptosis is mediated through modulating the extrinsic and intrinsic signaling pathways. Intriguingly, the p53 inhibitor (pifithrin-α), anti-Fas ligand (FasL) mAb, and specific inhibitors of caspase-8 (z-IETD-fmk), caspase-9 (z-LEHD-fmk), and caspase-3 (z-DEVD-fmk) blocked SLE- and diosgenin-reduced cell viability of WEHI-3 cells. Thein vivostudy demonstrated that SLE has marked antitumor efficacy against tumors in the WEHI-3 cell allograft model. In conclusion, SLE- and diosgenin-inducedG0/G1phase arrest and triggered extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells. SLE also exhibited antitumor activityin vivo. Our findings showed that SLE may be potentially efficacious in the treatment of leukemia in the future.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Solanum lyratumExtracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor

Yang

Kuo

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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“…AD-1, a ginsenoside derivative, showed apoptotic activity on lung cancer cells via activation of ERK pathway [44]. Some widely used famous chemotherapeutics [45] or compounds from natural plants [46], [47] showed apoptotic activity via activating phosphorylation of ERK in cancer cells. Moreover, some triterpenoid saponins showed other kinds of anti-tumor activity via ERK phosphorylation in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The Apoptotic Effect of D Rhamnose β-Hederin, a Novel Oleanane-Type Triterpenoid Saponin on Breast Cancer Cells

et al. 2014

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There is growing interest in development of natural products as anti-cancer and chemopreventive agents. Many triterpenoids have been proved as potential agents for chemoprevention and therapy of breast cancer. Ginsenosides from ginseng, which mostly belong to dammarane-type triterpenoids, have gained great attention for their anti-breast cancer activity with diverse mechanisms. However, studies of other kinds of triterpenoid saponins on breast cancer are limited. Previously, we purified and identified a novel oleanane-type triterpene saponin named D Rhamnose β-hederin (DRβ-H) from Clematis ganpiniana, a Chinese traditional anti-tumor herb. In the present study, DRβ-H showed strong inhibitory activity on the growth of various breast cancer cells and induced apoptosis in these cells. DRβ-H inhibited PI3K/AKT and activated ERK signaling pathway. PI3K inhibitor LY294002 synergistically enhanced DRβ-H-induced apoptosis whereas MEK inhibitor U0126 reduced the apoptosis rate. Moreover, DRβ-H regulated the ratio of pro-apoptotic and anti-apoptotic Bcl-2 family proteins. Furthermore, DRβ-H induced depolarization of mitochondrial membrane potential which released Apaf-1 and Cytochrome C from the inter membrane space into the cytosol, where they promoted caspase-9 and caspase-3 activation. This is the first report on the pro-apoptotic effects of DRβ-H, a novel oleanane-type triterpenoid saponin, on breast cancer cells and its comprehensive apoptosis pathways. It implied that oleanane-type triterpenoid saponin DRβ-H could be a promising candidate for chemotherapy of breast cancer.

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“…The increase in Bax can decrease the mitochondrial potential [37] which will make the cells bioenergytically deficient and subsequently leading to cell death. In a typical apoptotic program, the alterations in Bax could result the release of cytochrome-c from mitochondria and the accumulation of cytochrome-c in cytosol interacts with Apaf-1 and procaspase-9 leading to the formation of apoptosome which could cleaves and induces the inactivation of PARP [38][39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic mice

Colón¹,

Basha²,

Madero-Visbal³

et al. 2009

Invest New Drugs

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The nonsteroidal anti-inflammatory drug (NSAID), tolfenamic acid (TA) is emerging as a new anti-cancer agent. TA induces the degradation of specific Specificity protein (Sp) transcription factors, Sp1, Sp3 and Sp4 which are associated with tumor growth and metastasis. In this study we have evaluated the effect of TA on lung cancer using both in vitro and in vivo models. TA in a dose dependent manner inhibited proliferation and cell viability of two different lung cancer cells, A549 and CRL5803. TA treatment for 48 h significantly decreased the expression of Sp1, Sp3 and Sp4. The hepatocyte growth factor receptor, c-Met is overexpressed in a variety of cancers including lung cancer and Sp proteins mediate the regulation of c-Met. TA diminished the expression of c-Met protein and modulates its downstream signaling pathway. Furthermore, TA treatment significantly increased the number of apoptotic cells and pro-apoptotic markers c-PARP and Bax confirming the activation of apoptotic pathways. In vivo studies using the orthotopic mice model for lung cancer showed that TA (25 mg/kg/2 days and 50 mg/kg/2 days) resulted in a dose dependent decrease in tumor formation. The immunohistochemical staining of lung tissue showed high expression of Sp1, Sp3, Sp4, c-Met and phospho Met in control group and a dose dependent decrease in TA treated groups. The crucial findings of this study support that targeting c-Met with a potent inhibitor of Sp proteins is a robust strategy for the implications in lung cancer treatment and TA can serve as a therapeutic agent for this devastating disease.

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Caspase and mitogen activated protein kinase pathways are involved in Solanum lyratum herba induced apoptosis

Cited by 14 publications

References 12 publications

Solanum lyratumExtracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor

Solanum lyratumExtracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor

The Apoptotic Effect of D Rhamnose β-Hederin, a Novel Oleanane-Type Triterpenoid Saponin on Breast Cancer Cells

Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic mice

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