Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (9): 1025-1038.doi: 10.3736/jcim20120912

Previous Articles     Next Articles

Chelidonine isolated from ethanolic extract of Chelidonium majus promotes apoptosis in HeLa cells through p38-p53 and PI3K/AKT signalling pathways

Avijit Paul1, Kausik Bishayee1, Samrat Ghosh1, Avinaba Mukherjee1, Sourav Sikdar1, Debrup Chakraborty1, Naoual Boujedaini2, Khuda-Bukhsh Anisur Rahman1()   

  1. 1. Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India
    2. Boiron Laboratory, Lyon, France
  • Received:2012-02-16 Accepted:2012-04-10 Online:2012-09-20 Published:2018-09-15
  • Contact: Rahman Khuda-Bukhsh Anisur E-mail:prof_arkb@yahoo.co.in

Objective: To evaluate the role of chelidonine isolated from ethanolic extract of Chelidonium majus in inducing apoptosis in HeLa cells and to assess the main signalling pathways involved.

Methods: Cells were initially treated with different concentrations of chelidonine for 48 h and the median lethal dose (LD50) value was selected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Morphological analysis of nuclear condensation and DNA damage and fragmentation were measured by 4′,6-diamidino-2-phenylindole staining and comet assay. Further, reactive oxygen species (ROS) generation, cell cycle arrest and change in mitochondrial membrane potential were also examined and analyzed by flow cytometry. Evaluation of interaction of drug with CT DNA was investigated by circular dichroism (CD) spectral analysis to find any possible drug-CT DNA interaction. The mRNA and protein expressions of major signal proteins like p38, p53, protein kinase B (AKT), phosphatidylinositol 3-kinases (PI3K), Janus kinase 3 (JAK3), signal transducer and activator of transcription 3 (STAT3) and E6 and E7 oncoproteins as well as the pro-apoptotic genes and antiapoptotic genes were also estimated by reverse transcriptase-polymerase chain reaction and Western blotting.

Results: Based on LD50 value (30 μg/mL) of chelidonine, three doses were selected, namely, 22.5 μg/mL (D1), 30.0 μg/mL (D2) and 37.5 μg/mL (D3). Results showed that chelidonine inhibited proliferation and induced apoptosis in HeLa cells through generation of ROS, cell cycle arrest at sub-G1 and G0/G1 stage, change in mitochondrial membrane potential and fragmentation of DNA. Results of CD spectra showed effective interaction between chelidonine and calf thymus DNA. Studies of signalling pathway revealed that chelidonine could efficiently induce apoptosis through up-regulation of expressions of p38, p53 and other pro-apoptotic genes and down-regulation of expressions of AKT, PI3K, JAK3, STAT3, E6, E7 and other antiapoptotic genes.

Conclusion: Chelidonine isolated from Chelidonium majus efficiently induced apoptosis in HeLa cells through possible alteration of p38-p53 and AKT/PI3 kinase signalling pathways.

Key words: chelidonine, Chelidonium majus, antineoplastic agents, phytogenic, signal transducing, apoptosis, HeLa cells

"

Primer name Primer sequences
Caspase 3 Forward: 5′-AGGGGTCATTTATGGGACA-3′
Reverse: 5′-TACACGGGATCTGTTTCTTTG-3′
PARP-1 Forward: 5′-GATTCCCCATCTCTTTCTTTACACA -3′
Reverse: 5′-GGGCAATAGTCATCACAGACGTT-3′
PI3K Forward: 5′-TTAAACGCGAAGGCAACGA-3′
Reverse: 5′-CAGTCTCCTCCTGCTGCTGAT-3′
AKT Forward: 5′-CCTGGACTACCTGCACTCTCGGAA-3′
Reverse: 5′-TTGCTTTCAGGGCTGCTCAAGAAGG-3′
Bax Forward: 5′-AGTAACATGGAGCTGCAGAGG-3′
Reverse: 5′-ATGGTTCTGATCAGTTCCGG-3′
Bcl-2 Forward: 5′-GTGACTTCCGATCAGGAAGG-3′
Reverse: 5′-CTTCCAGACATTCGGAGACC-3′
ICAD Forward: 5′-ATGGTCAAGCCCAGACAGAG-3′
Reverse: 5′-CGTGTTTTCAACATTTAATGCAA-3′
p53 Forward: 5′-GGAAATTTGTATCCCGAGTATCTG -3′
Reverse: 5′-GTCTTCCAGTGTGATGATGGTAA-3′
GAPDH Forward: 5′-CCCACTAACATCAAATGGGG-3′
Reverse: 5′-CCTTCCACAATGCAAAGTT-3′

Figure 1

Mass spectroscopic data of isolated chelidonine and the chemical structure"

Figure 2

Effects of different concentrations of chelidonine on HeLa cells incubated for 48 h tested by MTT assayData were expressed as mean±standard error of mean. Values were measured in three independent experiments done in triplicate. **P<0.01, vs control group. MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide."

Figure 3

Effects of different concentration of chelidonine on normal peripheral blood mononuclear cells incubated for 48 h tested by MTT assayData were expressed as mean±standard error of mean. Values were measured in three independent experiments done in triplicate. *P<0.05, **P<0.01, vs control group. MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide."

"

Group n Apoptotic percentage Necrotic percentage
Control 3 20.278±0.003 3.307±0.003
D1 (22.5 μg/mL) 3 40.435±0.024** 4.467±0.005**
D2 (30.0 μg/mL) 3 44.037±0.009** 6.459±0.007**
D3 (37.5 μg/mL) 3 45.207±0.023** 10.333±0.004**

Figure 4

Morphological changes of HeLa cells for 48 h of treatment (phase-contrast microscopy, ×100) D1: 22.5 μg/mL; D2: 30.0 μg/mL; D3: 37.5 μg/mL. "

Figure 5

Control and drug-treated cells stained with DAPI (fluorescence microscopy, ×200) D1: 22.5 μg/mL; D2: 30.0 μg/mL; D3: 37.5 μg/mL. DAPI: 4′,6-diamidino-2-phenylindole. "

Figure 6

Control and drug-treated cells stained with AO-EB (fluorescence microscopy, ×200) D1: 22.5 μg/mL; D2: 30.0 μg/mL; D3: 37.5 μg/mL. AO-EB: acrydine orange-ethidium bromide. "

Figure 7

DNA damage tested by comet assay (fluorescence microscopy, ×200) D1: 22.5 μg/mL; D2: 30.0 μg/mL; D3: 37.5 μg/mL. "

Figure 8

DNA fragmentation assay of HeLa cells treated for 48 h of treatmentD1: 22.5 μg/mL; D2: 30.0 μg/mL; D3: 37.5 μg/mL. "

Figure 9

Circular dichroism spectra of calf thymus DNA incubated with chelidonine"

Figure 10

FACS analysis by annexin V-FITC/PI assayApoptotic cells (annexin V-FITC/PI) were analyzed by FACS and dot plots display Annexin V fluorescence (X-axis) versus PI fluorescence (Y-axis) with respect to the control cells after 48 h of treatment. D1: 22.5 μg/mL; D2: 30.0 μg/mL; D3: 37.5 μg/mL. FACS: fluorescence-activated cell sorter; FITC: fluorescein isothiocyanate; PI: propidium iodide. "

Figure 11

FACS analysis for cell cycle arrest in HeLa cellsCells were harvested and processed for cell cycle analysis using PI. Cell cycle phase distribution of HeLa cell nuclear DNA was determined by single label by FACS. Histogram display of DNA content (X-axis, PI fluorescence) versus counts (Y-axis) has been shown (sub-G1, G0/G1, S, and G2/M) for 48 h of treatment. D1: 22.5 μg/mL; D2: 30.0 μg/mL; D3: 37.5 μg/mL. FACS: fluorescence-activated cell sorter; PI: propidium iodide. "

Figure 12

ROS generation in HeLa cells observed by fluorescence microscopic observation and measured by FACS analysis =A: Fluorescence microscopic observation of ROS generation in HeLa cells (×200); B: FACS analysis of ROS generation in the D1-, D2-, and D3-treated cells with respect to the control cells. Control and treated cells were incubated with H2DCHF-DA fluorescent probe and analyzed in a single labelling FACS system at 530 nm band pass filter using histogram plot. D1: 22.5 μg/mL; D2: 30.0 μg/mL; D3: 37.5 μg/mL. ROS: reactive oxygen species; FACS: fluorescence-activated cell sorter; PI: propidium iodide; DCHF-DA: 2′,7′-dichlorodihydrofluor-escein diacetate."

Figure 13

FACS analysis of changes in MMP in HeLa cells Control and treated cells were incubated with Rhodamine 123 fluorescent probe and analyzed in a single labelling FACS system at 530 nm band pass filter using histogram plot. D1: 22.5 μg/mL; D2: 30.0 μg/mL; D3: 37.5 μg/mL. FACS: fluorescence-activated cell sorter; MMP: mitochondrial membrane potential."

Figure 14

Western blot analysis of p38, p53, caspase 3, PI3K, E6, E7 and GAPDHThe expressions of p38, p53 and caspase3 were up-regulated in the drug-treated cells with respect to the control cells whereas PI3K expression was down-regulated. GAPDH acted as a house-keeping gene. Ln1: Control; Ln2: 22.5 μg/mL; Ln3: 30.0 μg/mL; Ln4: 37.5 μg/mL. PI3K: phosphatidylinositol 3-kinases; GAPDH: glyceraldehyde-3-phosphate dehydrogenase."

Figure 15

Up-regulated proteins and down-regulated proteins measured by ELISAA: Up-regulated protein expression. B: Down-regulated protein expression."

Figure 16

RT-PCR analysis of p53, Bax, caspase 3, PARP-1, PI3K, AKT, Bcl-2, ICAD and GAPDHThe expressions of p53, Bax, caspase 3 and PARP-1 were up-regulated in drug-treated cells with respect to the positive control while the expressions of PI3K, AKT, Bcl-2 and ICAD were down-regulated. GAPDH acted as a housekeeping gene. RT-PCR: reverse transcription-polymerase chain reaction; PARP-1: poly adenosine diphosphate ribose polymerase-1; PI3K: phosphatidyl inositol 3-kinase; AKT: protein kinase B; Bax: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; ICAD: inhibitor of caspase-activated DNase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase."

[1] Chelidonium majus L . milky sap can induce apoptosis in human cervical carcinoma HeLa cells but not in Chinese Hamster Ovary CHO cells[J]. Folia Histochem Cytobiol, 2008,46(1):79-83
[2] Moro PA, Cassetti F, Giugliano G, Falce MT, Mazzanti G, Menniti-Ippolito F, Raschetti R, Santuccio C . Hepatitis from greater celandine(Chelidonium majus L.): review of literature and report of a new case[J]. J Ethnopharmacol, 2009,124(2):328-332
doi: 10.1016/j.jep.2009.04.036
[3] Gilca M, Gaman L, Panait E, Stoian I, Atanasiu V . Chelidonium majus — an integrative review: traditional knowledge versus modern findings. Forsch Komplementmed. 2010; 17(5):241-248.
doi: 10.1159/000321397
[4] Biswas SJ, Khuda-Bukhsh AR . Effect of a homeopathic drug, Chelidonium, in amelioration of p-DAB induced hepatocarcinogenesis in mice[J]. BMC Complement Altern Med, 2002,24
[5] Biswas SJ, Khuda-Bukhsh AR . Evaluation of protective potentials of a potentized homeopathic drug, Chelidonium majus, during azo dye induced hepatocarcinogenesis in mice. Indian[J] Exp Biol. 2004; 42(7):698-714.
[6] Biswas SJ, Bhattacharjee N, Khuda-Bukhsh AR . Efficacy of a plant extract(Chelidonium majus L.) in combating induced hepatocarcinogenesis in mice[J]. Food Chem Toxicol, 2008,46(5):1474-1487
doi: 10.1016/j.fct.2007.12.009
[7] Kéry A, Horváth J, Nász I, Verzár-Petri G, Kulcsár G, Dán P . Antiviral alkaloid in Chelidonium majus L. Acta Pharm Hung. 1987; 57(1-2):19-25.
[8] Lenfeld J, Kroutil M, Marsálek E, Slavík J, Preininger V, Simánek V . Antiinflammatory activity of quaternary benzophenanthridine alkaloids from Chelidonium majus. Planta Med. 1981; 43(2):161-165.
doi: 10.1055/s-2007-971493
[9] Chelidonium majus L.( Papaveraceae)[J]. Pharmacol Res, 1996,33(2):127-134
doi: 10.1006/phrs.1996.0019
[10] Chelidonium majus L.( Ukrain)[J]. Drugs Exp Clin Res, 1992,18(Suppl):63-67
[11] Zemskov V, Prokopchuk O, Susak Y, Zemskov S, Tkachenko O, Hodysh Y, Nowicky W . Efficacy of ukrain in the treatment of pancreatic cancer[J]. Langenbecks Arch Surg, 2002,387(2):84-89
doi: 10.1007/s00423-002-0293-y
[12] Uglyanitsa KN, Nechiporenko NA, Nefyodov LI, Doroshenko YM, Brzosko W, Nowicky W . Results of Ukrain monotherapy of prostate cancer[J]. Drugs Exp Clin Res, 2000,26(5-6):191-193
[13] Kadan P, Korsh OB, Melnyk A . Ukrain therapy of recurrent breast cancer with lung metastases(case report)[J]. Drugs Exp Clin Res, 1996,22(3-5):243-245
[14] Panzer A, Joubert AM, Bianchi PC, Seegers JC . The antimitotic effects of Ukrain, a Chelidonium majus alkaloid derivative, are reversible in vitro. Cancer Lett. 2000; 150(1):85-92.
doi: 10.1016/S0304-3835(99)00375-4
[15] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D . Global cancer statistics[J]. CA Cancer J Clin, 2011,61(2):69-90
doi: 10.3322/caac.v61:2
[16] Green JA . Clinical trials in cancer[J]. Br J Cancer, 2011,104(10):1521-1522
doi: 10.1038/bjc.2011.137
[17] Chelidonium majus L . studied by different chromatographic techniques[J]. Chromatographia, 2006,63(Suppl 13):S81-S86
doi: 10.1365/s10337-006-0728-7
[18] Kim YM, Talanian RV, Billiar TR . Nitric oxide inhibits apoptosis by preventing increases in caspase-3-like activity via two distinct mechanisms[J]. J Biol Chem, 1997,272(49):31138-31148
doi: 10.1074/jbc.272.49.31138
[19] Morley N, Rapp A, Dittmar H, Salter L, Gould D, Greulich KO, Curnow A . UVA-induced apoptosis studied by the new apo/necro-Comet-assay which distinguishes viable, apoptotic and necrotic cells[J]. Mutagenesis, 2006,21(2):105-114
doi: 10.1093/mutage/gel004
[20] Biswas R, Mandal SK, Dutta S, Bhattacharyya SS, Boujedaini N, Khuda-Bukhsh AR . Thujone-rich fraction of Thuja occidentalis demonstrates major anti-cancer potentials: evidences from in vitro studies on A375 cells. Evid Based Complement Alternat Med. 2011; 2011:568148.
[21] Samadder A, Chakraborty D, De A, Bhattacharyya SS, Bhadra K, Khuda-Bukhsh AR . Possible signaling cascades involved in attenuation of alloxan-induced oxidative stress and hyperglycemia in mice by ethanolic extract of Syzygium jambolanum: drug-DNA interaction with calf thymus DNA as target[J]. Eur J Pharm Sci, 2011,44(3):207-217
doi: 10.1016/j.ejps.2011.07.012
[22] Mandal SK, Biswas R, Bhattacharyya SS, Paul S, Dutta S, Pathak S, Khuda-Bukhsh AR . Lycopodine from Lycopodium clavatum extract inhibits proliferation of HeLa cells through induction of apoptosis via caspase-3 activation[J]. Eur J Pharmacol, 2010,626(2-3):115-122
doi: 10.1016/j.ejphar.2009.09.033
[23] Yang SE, Hsieh MT, Tsai TH, Hsu SL . Effector mechanism of magnolol-induced apoptosis in human lung squamous carcinoma CH27 cells[J]. Br J Pharmacol, 2003,138(1):193-201
doi: 10.1038/sj.bjp.0705024
[24] Bhattacharyya SS, Paul S, Mandal SK, Banerjee A, Boujedaini N, Khuda-Bukhsh AR . A synthetic coumarin(4-methyl-7 hydroxy coumarin) has anti-cancer potentials against DMBA-induced skin cancer in mice[J]. Eur J Pharmacol, 2009,614(1-3):128-136
doi: 10.1016/j.ejphar.2009.04.015
[25] MacLean DB, Bell RA, Saunders JK, Chen CY, Manske RHF . Structures of three minor alkaloids of Fumaria officinalis L[J]. Can J Chem, 1969,47(19):3593-3599
doi: 10.1139/v69-594
[26] Isaacs JT . Apoptosis: translating theory to therapy for prostate cancer[J]. J Natl Cancer Inst, 2000,92(17):1367-1369
doi: 10.1093/jnci/92.17.1367
[27] Fruehauf JP, Meyskens FL Jr . Reactive oxygen species: a breath of life or death? Clin Cancer Res. 2007; 13(3):789-794.
doi: 10.1158/1078-0432.CCR-06-2082
[28] Löpez-Lázaro M . Dual role of hydrogen peroxide in cancer: possible relevance to cancer chemoprevention and therapy[J]. Cancer Lett, 2007,252(1):1-8
doi: 10.1016/j.canlet.2006.10.029
[29] Yip NC, Fombon IS, Liu P, Brown S, Kannappan V, Armesilla AL, Xu B, Cassidy J, Darling JL, Wang W . Disulfiram modulated ROS-MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties[J]. Br J Cancer, 2011,104(10):1564-1574
doi: 10.1038/bjc.2011.126
[30] Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM , O’Connor JM,Oleksijew A,Petros AM,Reed JC,Shen W,Tahir SK,Thompson CB,Tomaselli KJ,Wang B,Wendt MD,Zhang H,Fesik SW,Rosenberg SH.An inhibitor of Bcl-2 family proteins induces regression of solid tumours[J]. Nature, 2005,435(7042):677-681
doi: 10.1038/nature03579
[31] Chaudhari M, Jayaraj R, Bhaskar AS, Lakshmana Rao PV . Oxidative stress induction by T-2 toxin causes DNA damage and triggers apoptosis via caspase pathway in human cervical cancer cells[J]. Toxicology, 2009,262(2):153-161
doi: 10.1016/j.tox.2009.06.002
[32] Khan N, Afaq F, Syed DN, Mukhtar H . Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells[J]. Carcinogenesis, 2008,29(5):1049-1056
doi: 10.1093/carcin/bgn078
[33] Mauro MO, Sartori D, Oliveira RJ, Ishii PL, Mantovani MS, Ribeiro LR . Activity of selenium on cell proliferation, cytotoxicity, and apoptosis and on the expression of CASP9, BCL-XL and APC in intestinal adenocarcinoma cells[J]. Mutat Res, 2011,715(1-2):7-12
doi: 10.1016/j.mrfmmm.2011.06.015
[34] Tsujimoto Y, Shimizu S . Bcl-2 family: life-or-death switch[J]. FEBS Lett, 2000,466(1):6-10
doi: 10.1016/S0014-5793(99)01761-5
[35] Martinou JC, Desagher S, Antonsson B . Cytochrome c release from mitochondria: all or nothing[J]. Nat Cell Biol, 2000,2(3):E41-E43
doi: 10.1038/35004069
[36] Hong SJ, Dawson TM, Dawson VL . Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling[J]. Trends Pharmacol Sci, 2004,25(5):259-264
doi: 10.1016/j.tips.2004.03.005
[37] Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S . A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD[J]. Nature, 1998,391(6662):43-50
doi: 10.1038/34112
[38] Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME . Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery[J]. Cell, 1997,91(2):231-241
doi: 10.1016/S0092-8674(00)80405-5
[39] Grad JM, Zeng XR, Boise LH . Regulation of Bcl-xL: a little bit of this and a little bit of STAT[J]. Curr Opin Oncol, 2000,12(6):543-549
doi: 10.1097/00001622-200011000-00006
[40] Lowe SW, Lin AW . Apoptosis in cancer[J]. Carcinogenesis, 2000,21(3):485-495
doi: 10.1093/carcin/21.3.485
[41] Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, Majumder PK, Baselga J, Rosen N . AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity[J]. Cancer Cell, 2011,19(1):58-71
doi: 10.1016/j.ccr.2010.10.031
[42] Fehrmann F, Laimins LA . Human papillomaviruses: targeting differentiating epithelial cells for malignant transformation[J]. Oncogene, 2003,22(33):5201-5207
doi: 10.1038/sj.onc.1206554
[43] Zhang C, Zhu H, Yang X, Lou J, Zhu D, Lu W, He Q, Yang B . P53 and p38 MAPK pathways are involved in MONCPT-induced cell cycle G2/M arrest in human non-small cell lung cancer A549[J]. J Cancer Res Clin Oncol, 2010,136(3):437-445
doi: 10.1007/s00432-009-0674-5
[44] Wagner EF, Nebreda AR . Signal integration by JNK and p38 MAPK pathways in cancer development[J]. Nat Rev Cancer, 2009,9(8):537-549
doi: 10.1038/nrc2694
[45] Tanaka Y, Gavrielides MV, Mitsuuchi Y, Fujii T, Kazanietz MG . Protein kinase C promotes apoptosis in LNCaP prostate cancer cells through activation of p38 MAPK and inhibition of the Akt survival pathway[J]. J Biol Chem, 2003,278(36):33753-33762
doi: 10.1074/jbc.M303313200
[46] Ahmed ST, Mayer A, Ji JD, Ivashkiv LB . Inhibition of IL-6 signaling by a p38-dependent pathway occurs in the absence of new protein synjournal[J]. J Leukoc Biol, 2002,72(1):154-162
[1] Cai-lian Fana, Wan-jun Caib, Meng-nan Ye, Miao Chen, Yi Dai. Qili Qiangxin, a compound herbal medicine formula, alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro. Journal of Integrative Medicine, 2022, 20(4): 365-375.
[2] Hong-xiao Li, Ling Shi, Shang-jie Liang Chen-chen Fang, Qian-qian Xu, Ge Lu, Qian Wang, Jie Cheng, Jie Shen, Mei-hong Shen. Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway. Journal of Integrative Medicine, 2022, 20(2): 163-172.
[3] Mohamed S. Othman, Sofian T. Obeidat, Amal H. Al-Bagawi, Mohamed A. Fareid, Alaa Fehaid, Ahmed E. Abdel Moneim. Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent#br#
#br#
. Journal of Integrative Medicine, 2022, 20(1): 65-72.
[4] Hyongjun Jeon, Hee-Young Kim, Chang-Hwan Bae, Yukyung Lee, Sungtae Koo, Seungtae Kim. Korean red ginseng decreases 1-methyl-4-phenylpyridinium-induced mitophagy in SH-SY5Y cells. Journal of Integrative Medicine, 2021, 19(6): 537-544.
[5] Porwornwisit Tritripmongkol, Tullayakorn Plengsuriyakarn, Mayuri Tarasuk, Kesara Na-Bangchang. In vitro cytotoxic and toxicological activities of ethanolic extract of Kaempferia galanga Linn. and its active component, ethyl-p-methoxycinnamate, against cholangiocarcinoma. Journal of Integrative Medicine, 2020, 18(4): 326-333.
[6] Varuni Colamba Pathiranage, Ira Thabrew, Sameera R. Samarakoon, Kamani H. Tennekoon, Umapriyatharshini Rajagopalan, Meran K. Ediriweera. Evaluation of anticancer effects of a pharmaceutically viable extract of a traditional polyherbal mixture against non-small-cell lung cancer cells. Journal of Integrative Medicine, 2020, 18(3): 242-252.
[7] Maged Mohamed Maher Abou-Hashem, Dina Mohamed Abo-elmatty, Noha Mostafa Mesbah, Ahmed Mohamed Abd EL-Mawgoud. Induction of sub-G0 arrest and apoptosis by seed extract of Moringa peregrina (Forssk.) Fiori in cervical and prostate cancer cell lines. Journal of Integrative Medicine, 2019, 17(6): 410-422.
[8] Supakanya Kumkarnjana, Rutt Suttisri, Ubonthip Nimmannit, Apirada Sucontphunt, Mattaka Khongkow, Thongchai Koobkokkruad, Nontima Vardhanabhuti. Flavonoids kaempferide and 4,2′-dihydroxy-4′,5′,6′-trimethoxychalcone inhibit mitotic clonal expansion and induce apoptosis during the early phase of adipogenesis in 3T3-L1 cells. Journal of Integrative Medicine, 2019, 17(4): 288-295.
[9] Shriniwas S. Basaiyye, Sanjay Kashyap, Kannan Krishnamurthi, Saravanadevi Sivanesan. Induction of apoptosis in leukemic cells by the alkaloid extract of garden cress (Lepidium sativum L.). Journal of Integrative Medicine, 2019, 17(3): 221-228.
[10] Carlos R. Oliveira, Daniel G. Spindola, Daniel M. Garcia, Adolfo Erustes, Alexandre Bechara, Caroline Palmeira-dos-Santos, Soraya S. Smaili, Gustavo J.S. Pereira, André Hinsberger, Ezequiel P. Viriato, Maria Cristina Marcucci, Alexandra C.H.F. Sawaya, Samantha L. Tomaz, Elaine G. Rodrigues, Claudia Bincoletto. Medicinal properties of Angelica archangelica root extract: Cytotoxicity in breast cancer cells and its protective effects against in vivo tumor development. Journal of Integrative Medicine, 2019, 17(2): 132-140.
[11] Bruno José Martins Da Silva, Sandro Wilson Gomes Pereira, Ana Paula Drummond Rodrigues, José Luiz Martins Do Nascimento, Edilene Oliveira Silva. In vitro antileishmanial effects of Physalis angulata root extract on Leishmania infantum. Journal of Integrative Medicine, 2018, 16(6): 404-410.
[12] Eric Wei Chiang Chan, Siu Kuin Wong, Hung Tuck Chan . Casticin from Vitex species: A short review on its anticancer and anti-inflammatory properties. Journal of Integrative Medicine, 2018, 16(3): 147-152.
[13] Jesmin Mondal, Jayeeta Das, Rajesh Shah, Anisur Rahman Khuda-Bukhsh. A homeopathic nosode, Hepatitis C 30 demonstrates anticancer effect against liver cancer cells in vitro by modulating telomerase and topoisomerase II activities as also by promoting apoptosis via intrinsic mitochondrial pathway. Journal of Integrative Medicine, 2016, 14(3): 209-218.
[14] Jesmin Mondal, Asmita Samadder, Anisur Rahman Khuda-Bukhsh. Psorinum 6× triggers apoptosis signals in human lung cancer cells. Journal of Integrative Medicine, 2016, 14(2): 143-153.
[15] Qing-qing Zang, Lu Zhang, Ning Gao, Cheng Huang. Ophiopogonin D inhibits cell proliferation, causes cell cycle arrest at G2/M, and induces apoptosis in human breast carcinoma MCF-7 cells. Journal of Integrative Medicine, 2016, 14(1): 51-59.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)". Journal of Chinese Integrative Medicine, 2008, 6(1): 15-21
[2] Yi-ting He, Qing-lin Zha, Jian-ping Yu, Yong Tan, Cheng Lu, Ai-ping Lv. Principal factor analysis of symptoms of rheumatoid arthritis and their correlations with efficacy of traditional Chinese medicine and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 32-36
[3] Jun Cai, Hua Wang, Sheng Zhou, Bin Wu, Hua-rong Song, Zheng-rong Xuan. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2008, 6(1): 37-40
[4] Wei Zhang, Xiang-feng Lu, Xiao-mei Zhang, Jian-jun Wu, Liang-duo Jiang. A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation. Journal of Chinese Integrative Medicine, 2008, 6(1): 60-67
[5] A-gao Zhou, Yong Zhang, Gang Kui, De-Yun Kong, Hai-liang Ge, Qiu-hua Ren, Jia-rong Dong, Sheng Hong, Xu-ming Mao, Yin Wang, Hui-zheng Zhang, Shu-jun Wang. Influence of traditional Chinese compound recipes with different efficacy on body weight, tumor weight and immune function in H22 cancer-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 77-82
[6] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[7] Li Zhou, Hong-xing Zhang, Ling-guang Liu, Wen-jun Wan. Effect of electro-acupuncture at Fenglong (GV 16) on nitric oxide and endothelin in rats with hyperlipidemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 89-92
[8] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. Guiding principles of clinical research on mild cognitive impairment (protocol). Journal of Chinese Integrative Medicine, 2008, 6(1): 9-14
[9] Xin-jun Wang, Ling-ling Wang . A mechanism of endogenous opioid peptides for rapid onset of acupuncture effect in treatment of depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1014-1017
[10] Bo Wang , Wei Yan , Li-hui Hou, Xiao-ke Wu. Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients with polycystic ovary syndrome. Journal of Chinese Integrative Medicine, 2010, 8(11): 1018-1022