Cytotoxicity of Triterpenes Isolated from Aceriphyllum rossii

Lee, Ik‐Soo; Yoo, Jae Won; Na, MinKyun; Min, Byung Sun; Lee, JongPill; Yun, Bong Sik; Jin, Wenyi; Kim, Hong-Jin; Youn, UiJung; Chen, Quan Cheng; Song, Kyung Sik; Seong, Yeon Hee; Bae, KiHwan

doi:10.1248/cpb.55.1376

Cited by 32 publications

(26 citation statements)

References 12 publications

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“…[1] In the literature available, there are insufficient data about the pharmacological properties of gypsogenic acid. Lee et al .,[2] isolated this compound from Aceriphyllum rossii and evaluated it for in vitro cytotoxicity against the K-562 and HL-60 cell lines. [2]…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of gypsogenic acid isolated from Gypsophila trichotoma

et al. 2014

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Background:Gypsophila trichotoma Wend. (Caryophyllaceae) is a medicinal plant which is protected in Bulgaria by the Biodiversity Law. Previous studies have showed the presence of triterpene saponins, sterols, flavonoids, triterpens, etc.Objective:Gypsogenic acid, isolated from Gypsophila trichotoma roots, was evaluated for cytotoxic activity.Materials and Methods:The structure of the compound was elucidated by spectral methods. The cell survival fraction was determined by the MTT dye reduction assay, performed with some modifications.Results:Gypsogenic acid was tested in a panel of human tumor cell lines and was found to inhibit the proliferation of malignant cells. It was active against leukemic cells with lymphoid (SKW-3 and BV-173) or myeloid phenotype (HL-60, K-562, and LAMA-84), as well as against the EJ bladder carcinoma cell line. Bcr-Abl expressing myeloid cells (LAMA-84 and especially K-562) displayed lower sensitivity. HL-60/Dox cells were less sensitive to gypsogenic acid than the parent cell line, which shows that gypsogenic acid is probably a substrate of MRP-1.

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Section: Introductionmentioning

confidence: 99%

Cytotoxicity of gypsogenic acid isolated from Gypsophila trichotoma

et al. 2014

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“…The Cytotoxicity of 3-OA on Various Cancer Cells In a previous study, 15) we reported that 3-OA is cytotoxic to HL-60 and K562 cancer cells. We initiated the present study by examining the cytotoxicity of 3-OA (structure shown in Fig.…”

Section: Resultsmentioning

confidence: 94%

“…RNA (2 mg) was reverse-transcribed (RT) from each sample using MuLV reverse transcriptase, 1 mM dNTP, and oligo (dT [12][13][14][15][16][17][18] ) 0.5 mg/ml. Polymerase chain reaction (PCR) analyses were performed on aliquots of the cDNA preparations to detect FasL, Fas, FADD, and cFLIP (using b-actin as an internal standard) gene expression using a thermal cycler (Perkin Elmer Cetus, Foster City, CA, U.S.A.).…”

Section: Methodsmentioning

confidence: 99%

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3-Oxoolean-12-en-27-oic Acid Isolated from Aceriphyllum rossii Induces Caspase-8-Dependent Apoptosis in Human Promyelocytic Leukemia HL-60 Cells

Kim

Won

Kim³

et al. 2009

Biological & Pharmaceutical Bulletin

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Information on the molecular mechanisms of drug action is essential for the development of any potential chemotherapeutic. In this context, several cancer drugs have been shown to induce apoptosis in tumor cells.1) Apoptosis, known as programmed cell death, is a highly organized cell death process that is characterized by distinct morphological features, such as, cell shrinkage, chromatin condensation, plasma membrane blebbing, DNA fragmentation, and the breakdown of cells into smaller units (apoptotic bodies). 2)Many investigators have demonstrated that apoptosis is regulated by two major pathways. [3][4][5] The first pathway occurs via death receptors on the cell surface, such as, TNFR1 (tumor necrosis factor receptor 1) and Fas, the latter of which can directly activate procaspase-8 by DISC (death-inducing signaling complex), which includes the cytoplasmic tails of Fas receptors and procaspase-8.4) Caspase-8, in turn, activates the proteolytic caspase cascade that transmits and amplifies death signals by activating apoptotic executioner caspases like caspase-3 and -7. These executioner caspases then cleave several substrate proteins including poly (ADP-ribose) polymerase-1 (PARP-1), which results in the self-destruction of cells.6) Furthermore, interaction between Fas and FasL induces apoptotic cell death and altered levels of Fas/FasL expression have been implicated in the pathogenesis of diseases associated with immune regulation. 7,8) The second pathway regulates the apoptotic cascade via a convergence of signaling at mitochondria, such as, those signals mediated by Bcl-2 family proteins. This pathway involves altered mitochondrial membrane potentials, the release of cytochrome c into the cytosol, and the activation of procaspase-9, which is followed by the activations of effector caspases like caspase-3 and -7.5) The mitochondrial pathway, driven by Bcl-2 family proteins, may involves anti-apoptotic (Bcl-2 and Bcl-xL) or pro-apoptotic (Bax, Bak, and Bid), and regulates cell death by controlling mitochondrial membrane permeability during apoptosis. 9)Triterpenoids derived from plants are used for medicinal purposes in many Asian countries and some have been reported to have anti-tumor activity.10) Moreover, it was recently found that the novel synthetic triterpenoid methyl-2-cyano-3,12-dioxooleane-1,9-dien-28-oate potently induces caspase-mediated apoptosis in human lung cancer cells. 11)Furthermore, it is also known that the phytoterpenoid 3-oxoolean-12-en-27-oic acid (3-OA, a pentacyclic compound) is present in Aceriphyllum rossii ENGLER (Saxifragaceae), which grows in scant amounts in damp rocky areas in valleys in the central northern region of Korea.12) During recent years, pharmacological characterizations of 3-OA have concluded that it has several biological activities, which include; the protein tyrosine phosphatase 1B inhibitory activity, 13) acylCoA:cholesterol acyltransferase (ACAT) inhibitory activity, 12) and anti-complementary activity. 14) Furthermore, it has been demonstrated that 3-OA is c...

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“…The young leaflets and stems have been used for food. 11) We previously isolated new triterpene 3a,23-isopropylidenedioxyolean-12-en-27-oic acid (IPA) (Fig. 1A) from A. rossii and IPA exhibited considerable cytotoxicity against human leukemia K562 and HL-60 cells.…”

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confidence: 99%

3.ALPHA.,23-Isopropylidenedioxyolean-12-en-27-oic Acid, a Triterpene Isolated from Aceriphyllum rossii, Induces Apoptosis in Human Cervical Cancer HeLa Cells through Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

Won

Chung

et al. 2010

Biological & Pharmaceutical Bulletin

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Despite of the widespread use of the Papanicolaou smear and HPV (human papollomavirus) vaccine, cervical cancer remains the most common cancer in women under 45 years of age in developing countries. Furthermore, almost half of all women with invasive cervical cancer are diagnosed at a late stage. Accordingly, there is an urgent need to identify an agent that can be used alone or in combination with a conventional anti-cancer drug like cisplatin, to improve the prognosis of this disease. 1)Apoptosis, a morphologically and biochemically defined form of cell death, plays a key role in the regulation of the growth of normal and neoplastic tissues.2) Recent studies have amply documented that two major pathways are involved in the regulation of apoptosis. The extrinsic apoptotic pathway involves cell surface death receptors such as Fas/CD95 and tumor necrosis factor receptor 1, 2 (TNFR1, 2), which upon activation up-regulate downstream signaling cascade including the activation of caspase-8.2) The intrinsic pathway is dependent on various cell stress stimuli leading to altered ratio of Bcl-2 family members affecting the release of cytochrome c and apoptotic protease activating factor-1 (Apaf-1) that leads to caspase-9 activation.3) The active forms of caspase-8 and -9 may activate downstream effector caspases-3, -6, and -7, resulting in the cleavage of several intracellular polypeptides (e.g., PARP-1) as well as activation of DNase that leads to DNA fragmentation.Endoplasmic reticulum (ER) is a central organelle engaged in lipid synthesis and protein folding and maturation. A variety of toxic insults, including failure of protein synthesis, folding, and degradation and Ca 2ϩ overload, can disturb the ER function and result in ER stress. 4,5) Under normal conditions, the ER stress sensors (IRE1, PERK, and ATF6) reside with binding to glucose-regulated protein 78 (GRP78). When ER stress occurred, the sensors dissociate with GRP78 and transfer downstream signals to the cytoplasm. As a consequence, these compensatory responses contribute to the reduction of ER overload and functions to protect cells against ER stress. However, if the ER functions are severely affected, cells are removed by apoptosis. ER stress-mediated apoptosis is triggered by the activation of ER membrane resident caspase-12 and induction of growth arrest DNA damageinducible gene 153 (GADD153).6,7) Calpains (a family of Ca 2ϩ -dependent intracellular cysteine proteases) are also implicated in ER stress-induced apoptosis. There are ubiquitously expressed calpain I (m-calpain) and calpain II (m-calpain) proteases. A recent study has shown that ubiquitous calpains promote caspase-12 and c-Jun N-terminal kinase (JNK) activation during ER stress-induced apoptosis. 8)Numerous naturally occurring substances are recognized to be anti-oxidants, cancer preventive agents, or even antitumor agent such as paclitaxel.9) Triterpenes are part of a family of naturally occurring compounds and present a wide spectrum of pharmacological activities, with one of the most elu...

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Cytotoxicity of Triterpenes Isolated from Aceriphyllum rossii

Cited by 32 publications

References 12 publications

Cytotoxicity of gypsogenic acid isolated from Gypsophila trichotoma

Cytotoxicity of gypsogenic acid isolated from Gypsophila trichotoma

3-Oxoolean-12-en-27-oic Acid Isolated from Aceriphyllum rossii Induces Caspase-8-Dependent Apoptosis in Human Promyelocytic Leukemia HL-60 Cells

3.ALPHA.,23-Isopropylidenedioxyolean-12-en-27-oic Acid, a Triterpene Isolated from Aceriphyllum rossii, Induces Apoptosis in Human Cervical Cancer HeLa Cells through Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

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