Prevention of liver carcinogenesis by amarogentin through modulation of G1/S cell cycle check point and induction of apoptosis

被引:45
|
作者
Pal, Debolina [1 ]
Sur, Subhayan [1 ]
Mandal, Suvra [2 ]
Das, Ashes [2 ]
Roy, Anup [3 ]
Das, Sukta [1 ]
Panda, Chinmay Kumar [1 ]
机构
[1] Chittaranjan Natl Canc Inst, Dept Oncogene Regulat, Kolkata 700026, India
[2] Natl Res Inst Ayurved Drug Dev, Dept Chem, Kolkata, India
[3] N Bengal Med Coll & Hosp, Siliguri, W Bengal, India
关键词
HEPATOCELLULAR-CARCINOMA; PROGNOSTIC-SIGNIFICANCE; FREQUENT ALTERATIONS; DOWN-REGULATION; IN-VIVO; EXPRESSION; CANCER; OVEREXPRESSION; INHIBITION; SURVIVAL;
D O I
10.1093/carcin/bgs276
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Amarogentin, a secoiridoid glycoside, is an active component of the medicinal plant Swertia chirata. In this study, chemopreventive and chemotherapeutic actions of amarogentin were evaluated in a carbon tetrachloride (CCl4)/N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis mouse model system during continuous and posttreatment schedule. Better survival, no toxicity and increased body weight were noted in amarogentin-treated mice. Reduction in proliferation and increase in apoptosis frequency were evident in amarogentin-treated groups. In carcinogen control group moderate dysplasia, severe dysplasia and hepatocellular carcinoma were evident at 10th, 20th and 30th week, respectively. Amarogentin was found to prevent progression of liver carcinogenesis at mild dysplastic stage. Exposure to CCl4/NDEA resulted in upregulation of ppRb807/811, cyclinD1 and cdc25A at 10th week and additional activation of cMyc and mdm2 along with downregulation of LIMD1, p53 and p21 at 20th week. This was followed by activation of ppRb567 and downregulation of Rbsp3 at 30th week. Prevention of carcinogenesis by amarogentin in both groups might be due to cumulative upregulation of LIMD1, RBSP3, p16 and downregulation of cdc25A at 10th week along with activation of p53 and p21 and downregulation of ppRb807/811 and ppRb567 at 20th week, followed by downregulation of cyclinD1, cMyc and mdm2 at 30th week. During carcinogenesis reduction of apoptosis was evident since 20th week. However, amarogentin treatment could significantly induce apoptosis through upregulation of the Bax-Bcl2 ratio, activation of caspase-3 and poly ADP ribose polymerase cleavage. This is the first report of chemopreventive/therapeutic role of amarogentin during liver carcinogenesis through modulation of cell cycle and apoptosis.
引用
收藏
页码:2424 / 2431
页数:8
相关论文
共 50 条
  • [21] Antiproliferative Activity of Gibbosic Acid H through Induction of G0/G1 Cell Cycle Arrest and Apoptosis in Human Lung Cancer Cells
    Han, Jaeho
    Kim, Donghwa
    Park, Hyen Joo
    Park, Hee-Juhn
    Lee, Sang Kook
    JOURNAL OF CANCER PREVENTION, 2023, 28 (04) : 201 - 211
  • [22] Antitumor effects of miconazole on human colon carcinoma xenografts in nude mice through induction of apoptosis and G0/G1 cell cycle arrest
    Wu, CH
    Jeng, JH
    Wang, YJ
    Tseng, CJ
    Liang, YC
    Chen, CH
    Lee, HM
    Lin, JK
    Lin, CH
    Lin, SY
    Li, CP
    Ho, YS
    TOXICOLOGY AND APPLIED PHARMACOLOGY, 2002, 180 (01) : 22 - 35
  • [23] Interference of Notch 2 inhibits the progression of gliomas and induces cell apoptosis by induction of the cell cycle at the G0/G1 phase
    Yu, Hui-Ping
    Qi, Song-Tao
    Feng, Wen-Feng
    Zhang, Guo-Zhong
    Zhang, He-Ping
    Tian, Jin-Jun
    MOLECULAR MEDICINE REPORTS, 2015, 11 (01) : 734 - 738
  • [24] Modeling of the G1/S transition in yeast cell cycle
    Barberis, M.
    Klipp, E.
    Vanoni, M.
    Alberghina, L.
    FEBS JOURNAL, 2007, 274 : 248 - 248
  • [25] A unified model for the G1/S cell cycle transition
    Hume, Samuel
    Dianov, Grigory L.
    Ramadan, Kristijan
    NUCLEIC ACIDS RESEARCH, 2020, 48 (22) : 12483 - 12501
  • [26] Inhibition of G1 to S cell cycle progression by BCCIβ
    Meng, XB
    Liu, JM
    Shen, ZY
    CELL CYCLE, 2004, 3 (03) : 343 - 348
  • [27] Proliferation characteristics in pediatric Hodgkin's disease point to a cell cycle arrest in G1 phase
    Tiemann, M
    Claviez, A
    Lueders, H
    Zimmermann, M
    Schellong, G
    Doerffel, W
    Parwaresch, R
    BLOOD, 2004, 104 (11) : 852A - 852A
  • [28] Proliferation characteristics in pediatric Hodgkin's lymphoma point to a cell cycle arrest in the G1 phase
    Tiemann, M
    Claviez, A
    Lüders, H
    Zimmermann, M
    Schellong, G
    Dörffel, W
    Parwaresch, R
    MODERN PATHOLOGY, 2005, 18 (11) : 1440 - 1447
  • [29] Commitment point during G0→G1 that controls entry into the cell cycle
    Lea, NC
    Orr, SJ
    Stoeber, K
    Williams, GH
    Lam, EWF
    Ibrahim, MAA
    Mufti, GJ
    Thomas, NSB
    MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (07) : 2351 - 2361
  • [30] GSNOR SAFEGUARDS G1/S CHECK-POINT, AND CONTROLS PROLIFERATION IN EMBRYONAL RHABDOMYOSARCOMA
    Larotondo, Giovanni
    Giglio, Paola
    Matrullo, Gianmarco
    Pecorari, Chiara
    Maiani, Emiliano
    Filomeni, Giuseppe
    Montagna, Costanza
    FREE RADICAL BIOLOGY AND MEDICINE, 2024, 218 : 52 - 53