Oleanolic Acid Induces Apoptosis in Human Leukemia Cells through Caspase Activation and Poly(ADP-ribose) Polymerase Cleavage

Zhang, Pengxia; Li, Hongmei; Chen, Dong; Ni, Jing; Kang, Yu‐Ming; Wang, Shuqiu

doi:10.1111/j.1745-7270.2007.00335.x

Cited by 69 publications

(51 citation statements)

References 19 publications

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“…[36][37][38] Also, a modified form of 3-taraxerone (3,4-seco-taraxerone) has shown cytotoxicity in the same human cell. 39 The experimental results obtained in our study demonstrate that RE shows a greater toxicity than LE, probably because of the presence of emodin.…”

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confidence: 99%

In VitroEvaluation of the Genotoxic Activity and Apoptosis Induction of the Extracts of Roots and Leaves from the Medicinal PlantCoccoloba mollis(Polygonaceae)

Tsuboy

Marcarini

Luiz

et al. 2010

Journal of Medicinal Food

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Coccoloba mollis (Family Polygonaceae) is a medicinal plant popularly used in cases of memory loss, stress, insomnia, anemia, impaired vision, and sexual impotence, but the scientific literature, to date, lacks studies on the biological effects of this species, particularly with regard to cytotoxicity and induction of DNA damage. The aim of the present study was to assess in vitro (in hepatic HTC cells) ethanolic extracts of the roots and leaves of C. mollis for cytotoxicity, genotoxicity, and induction of apoptosis. For these evaluations the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay, comet assay, micronucleus test with cytokinesis block, and an in situ test for detection of apoptotic cells with acridine orange staining were used. The results showed that the extract obtained from the roots of C. mollis is more cytotoxic than that obtained from the leaves and that the reduction in cell viability observed in the MTT assay was a result, at least in part, from the induction of apoptosis. Both extracts induced DNA damage at a concentration of 20 mg=mL in the comet assay, but no genotoxicity was detected with any of the treatments carried out in the micronucleus test.

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confidence: 99%

In VitroEvaluation of the Genotoxic Activity and Apoptosis Induction of the Extracts of Roots and Leaves from the Medicinal PlantCoccoloba mollis(Polygonaceae)

Tsuboy

Marcarini

Luiz

et al. 2010

Journal of Medicinal Food

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“…Considering its pleiotropic function and nontoxicity, researchers have been increasingly focused on OA and making efforts to improve its activity and drugability in recent decades (Liby Since that cancer-related deaths keep rising both in developed and developing countries in recent years, the anti-tumor property of OA receives more and more attention. Apoptosis induction has been well known as one of the major mechanisms underlying OA anti-tumor activity on various types of cancer cells (Juan et al, 2006;Martin et al, 2007;Zhang et al, 2007;Shyu et al, 2010;Yan et al, 2010;Feng et al, 2011b;Lucio et al, 2011;Pratheeshkumar et al, 2011;Zhou et al, 2011;Chakravarti et al, 2012;George et al, 2012;Gu et al, 2012;Struh et al, 2012;Wei et al, 2012;Wang et al, 2013). Mechanistically, OA treatment increases the ratio of proapoptotic protein, Bax, to anti-apoptotic protein, Bcl-2, in the outer mitochondrial membrane, facilitates the formation of Bax oligomer, increases the permeability of mitochondrial membrane, releases cytochrome C from inner membrane into cytosol, triggers the caspase pathway through activating Apaf-1, cleaves multiple cellular target molecules including Poly ADP ribose polymerase (PARP) and DNA, and eventually leads to cell death (Martin et al, 2007;Zhang et al, 2007;Shyu et al, 2010;Yan et al, 2010;Zhou et al, 2011;Chakravarti et al, 2012;Wei et al, 2012;Wang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid

Liu¹,

Wu²,

Ma³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Oleanolic acid (OA) is a nutritional component widely distributed in various vegetables. Although it has been well recognized for decades that OA exerts certain anti-tumor activity by inducing mitochondria-dependent apoptosis, it is still unclear that what molecular signaling is responsible for this effect. In this study, we employed cancer cell lines, A549, BXPC-3, PANC-1 and U2OS to elucidate the molecular mechanisms underlying OA antitumor activity. We found that activation of MAPK pathways, including p-38 MAPK, JNK and ERK, was triggered by OA in both a dose and time-dependent fashion in all the tested cancer cells. Activation was accompanied by cleavage of caspases and PARP as well as cytochrome C release. SB203580 (p38 MAPK inhibitor), but not SP600125 (JNK inhibitor) and U0126 (ERK inhibitor), rescued the pro-apoptotic effect of OA on A549 and BXPC-3 cells. OA induced p38 MAPK activation promoted mitochondrial translocation of Bax and Bim, and inhibited Bcl-2 function by enhancing their phosphorylation. OA can induce reactive oxygen species (ROS)-dependent ASK1 activation, and this event was indispensable for p38 MAPK-dependent apoptosis in cancer cells. In vivo, p38 MAPK knockdown A549 tumors proved resistant to the growth-inhibitory effect of OA. Collectively, we elucidated that activation of ROS/ASK1/p38 MAPK pathways is responsible for the apoptosis stimulated by OA in cancer cells. Our finding can contribute to a better understanding of molecular mechanisms underlying the antitumor activity of nutritional components.

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“…To understand the pathway of apoptotic cell death, results were compared with the literature and two major pathways of apoptotic cell death program have been identi- fied, namely receptor-mediated (extrinsic) and chemical-induced mitochondrial (intrinsic) apoptosis [20]. Zhang, et al [21] reported that OA induced apoptotic cell death on HL-60 cell lines and the apoptotic death is characterized by formation of apoptotic bodies, DNA fragmentation, increased of the number of cell in the sub G1 phase, activation of caspase 3 and 9 and cleavage of poly (ADP ribose) polymerase and Takashi et al [22] reported that OA inhibit the DNA topoisomerase, so the pathway of apoptotic death is extrinsic. Concerning the apoptotic effect of UA on HL-60, Beak et al demonstrated that UA induced genomic DNA fragmentation, a hallmark of apoptosis, indicating that the mechanism by which UA induced cell death was through apoptosis [23].…”

Section: Discussionmentioning

confidence: 99%

Apoptosis Induction by Cestrum parqui L’Hér. leaves on HL-60 Cell Line: Identification of Active Phytomolecules

Chenni¹,

Torres²,

Estévez³

et al. 2015

IJCR

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IntroductionCancer, one of the leading causes of human death, has attracted more attention due to the complexity of etiology, diagnosis and treatment [1]. In recent years, chemotherapeutic management against various types of cancer including leukemia has been increased rapidly though some times cancer cells resistance against chemotherapy [2,3]. In this respect, search for effective anticancer agent that inhibit the proliferation of the cells as well as inhibit the resistance nature of the cancer cells and induce differentiation of the monocytes is an ongoing challenge. Therefore to find out anticancer agent with multi-target efficacies, attention has been focused on plant products as the plant products have been used as remedies for several human diseases including cancer from ancient times with lower side effects [4]. The reasons for using them that they contain variety of chemical compounds usually secondary metabolites with therapeutic values [5]. Cestrum parqui is belonging to the family Solanaceae, usually known as "green or Chilean cestrum" in Tunisia, are rich in various secondary metabolites such as saponins, polyhydroxylated terpenes (C13 norisoprenoids, sesquiterpenes, spirostanes and pseudosapogenins) and ent-kaurene glycosides (parquin and carboxyparquin) [6][7][8]. Several scientific reports demonstrate that C. parqui exhibits a wide spectrum of pharmacological activity when administered systemically or in isolated organ preparations. For example, it is used to treat headache, rheumatic pain, scabies, dermatosis, diarrhaea and metrorraghia [7]. The plant is also used in Chilean folk Abstract Background: In our time, there is an urgent need to discover natural anticancer products without toxic side's effects. Objective: The present study was conducted to investigate the anticancer activity of the methanolic extract of Cestrum parqui leaves as well as identification of the active compounds in this concern. Materials and Methods: Eight column chromatographic fractions were tested against human leukaemia cell line (HL-60) and the cell viability was measured by dimethylthiazol tetrazolium assay. Studies of apoptosis, cell cycle and DNA fragmentation were carried out following the standard protocol. Effective fractions were analysed by high performance liquid chromatography-ultra violet, HPLC-evaporative light scattering detector and preparative-HPLC. Finally the active compounds were identified by gas chromatography coupled to mass spectrometry. Results: Out of eight, fraction II showed remarkable inhibition on the growth of HL-60 cell line and fraction I showed moderate activity on such inhibition. Mechanisms of the inhibition were identified as cell cycle arrestation and apoptosis induction by the said fractions. Chromatographic and mass spectrometric analysis of the fraction II indicated the presence of oleanolic and ursolic acids as biologically active compounds. Conclusion: This study is the first investigation that shows Cestrum parqui has anticancer activity and the responsible compounds are olea...

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Oleanolic Acid Induces Apoptosis in Human Leukemia Cells through Caspase Activation and Poly(ADP-ribose) Polymerase Cleavage

Cited by 69 publications

References 19 publications

In VitroEvaluation of the Genotoxic Activity and Apoptosis Induction of the Extracts of Roots and Leaves from the Medicinal PlantCoccoloba mollis(Polygonaceae)

In VitroEvaluation of the Genotoxic Activity and Apoptosis Induction of the Extracts of Roots and Leaves from the Medicinal PlantCoccoloba mollis(Polygonaceae)

p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid

Apoptosis Induction by Cestrum parqui L’Hér. leaves on HL-60 Cell Line: Identification of Active Phytomolecules

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