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Planta Med 2012; 78(08): 796-799
DOI: 10.1055/s-0031-1298463
Biological and Pharmacological Activity
Letters
Georg Thieme Verlag KG Stuttgart · New York

Anti-Austerity Agents from Rhizoma et Radix Notopterygii (Qianghuo)

Feng Li
1   Institute of Natural Medicine, University of Toyama, Toyama, Japan
,
Yukari Okamura
1   Institute of Natural Medicine, University of Toyama, Toyama, Japan
,
Dya Fita Dibwe
1   Institute of Natural Medicine, University of Toyama, Toyama, Japan
,
Suresh Awale
1   Institute of Natural Medicine, University of Toyama, Toyama, Japan
,
Shigetoshi Kadota
1   Institute of Natural Medicine, University of Toyama, Toyama, Japan
,
Yasuhiro Tezuka
1   Institute of Natural Medicine, University of Toyama, Toyama, Japan
› Author Affiliations
Further Information

Publication History

received 14 November 2011
revised 05 March 2012

accepted 28 March 2012

Publication Date:
19 April 2012 (online)

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Abstract

During a search for potent anticancer agents from natural products based on an anti-austerity strategy, we found that a CHCl3 extract of Rhizoma et Radix Notopterygii (Qianghuo), a Chinese crude drug, exhibited strong cytotoxicity against PANC-1 human pancreatic cancer cells, with a PC50 value of 17.5 µg/mL. Further fractionation and purification of this bioactive extract led to the isolation of 19 known compounds (1–19). The in vitro preferential cytotoxicity of the isolates was evaluated against two human pancreatic cancer cell lines, PANC-1 and PSN-1. Among the compounds isolated, ostruthin (7) displayed the most potent activity against both PANC-1 (PC50, 7.2 µM) and PSN-1 (PC50, 7.8 µM) cells in nutrient-deprived medium (NDM) and may have induced necrotic nutrient-deprived PANC-1 cell death.

Key words

Rhizoma et Radix Notopterygii - Notopterygium incisum Ting ex H. T. Chang - Notopterygium forbesii Boiss - Umbelliferae - anti-austerity strategy - pancreatic cancer

Supporting Information

 

  • References

  • 1 Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60: 277-300
    CrossrefPubMedSearch in Google Scholar
  • 2 Lonardo E, Hermann PC, Heeschen C. Pancreatic cancer stem cells – update and future perspectives. Mol Oncol 2010; 4: 431-442
    CrossrefPubMedSearch in Google Scholar
  • 3 Philip PA, Mooney M, Jaffe D, Eckhardt G, Moore M, Meropol N, Emens L, OʼReilly E, Korc M, Ellis L, Benedetti J, Rothenberg M, Willett C, Tempero M, Lowy A, Abbruzzese J, Simeone D, Hingorani S, Berlin J, Tepper J. Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment. J Clin Oncol 2009; 27: 5660-5669
    CrossrefPubMedSearch in Google Scholar
  • 4 Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25: 1960-1966
    CrossrefPubMedSearch in Google Scholar
  • 5 Izuishi K, Kato K, Ogura T, Kinoshita T, Esumi H. Remarkable tolerance of tumor cells to nutrient deprivation: possible new biochemical target for cancer therapy. Cancer Res 2000; 60: 6201-6207
    PubMedSearch in Google Scholar
  • 6 Esumi H, Izuishi K, Kato K, Hashimoto K, Kurashima Y, Kishimoto A, Ogura T, Ozawa T. Hypoxia and nitric oxide treatment confer tolerance to glucose starvation in a 5′-AMP-activated protein kinase-dependent manner. J Biol Chem 2002; 277: 32791-32798
    CrossrefPubMedSearch in Google Scholar
  • 7 Lu J, Kunimoto S, Yamazaki Y, Kaminishi M, Esumi H. Kigamicin D, a novel anticancer agent based on a new anti-austerity strategy targeting cancer cellsʼ tolerance to nutrient starvation. Cancer Sci 2004; 95: 547-552
    CrossrefPubMedSearch in Google Scholar
  • 8 Awale S, Lu J, Kalauni SK, Kurashima Y, Tezuka Y, Kadota S, Esumi H. Identification of arctigenin as an antitumor agent having the ability to eliminate the tolerance of cancer cells to nutrient starvation. Cancer Res 2006; 66: 1751-1757
    CrossrefPubMedSearch in Google Scholar
  • 9 Magolan J, Coster MJ. Targeting the resistance of pancreatic cancer cells to nutrient deprivation: anti-austerity compounds. Curr Drug Deliv 2010; 7: 355-369
    CrossrefPubMedSearch in Google Scholar
  • 10 Zaidi SF, Awale S, Kalauni SK, Tezuka Y, Esumi H, Kadota S. Diterpenes from “Pini Resina” and their preferential cytotoxic activity under nutrient-deprived condition. Planta Med 2006; 72: 1231-1234
    Thieme ConnectPubMedSearch in Google Scholar
  • 11 Awale S, Nakashima EM, Kalauni SK, Tezuka Y, Kurashima Y, Lu J, Esumi H, Kadota S. Angelmarin, a novel anti-cancer agent able to eliminate the tolerance of cancer cells to nutrient starvation. Bioorg Med Chem Lett 2006; 16: 581-583
    CrossrefPubMedSearch in Google Scholar
  • 12 Win NN, Awale S, Esumi H, Tezuka Y, Kadota S. Bioactive secondary metabolites from Boesenbergia pandurata of Myanmar and their preferential cytotoxicity against human pancreatic cancer PANC-1 cell line in nutrient-deprived medium. J Nat Prod 2007; 70: 1582-1587
    CrossrefPubMedSearch in Google Scholar
  • 13 Win NN, Awale S, Esumi H, Tezuka Y, Kadota S. Novel anticancer agents, kayeassamins C–I from the flower of Kayea assamica of Myanmar. Bioorg Med Chem 2008; 16: 8653-8660
    CrossrefPubMedSearch in Google Scholar
  • 14 Awale S, Li F, Onozuka H, Esumi H, Tezuka Y, Kadota S. Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition. Bioorg Med Chem 2008; 16: 181-189
    CrossrefPubMedSearch in Google Scholar
  • 15 Win NN, Awale S, Esumi H, Tezuka Y, Kadota S. Novel anticancer agents, kayeassamins A and B from the flower of Kayea assamica of Myanmar. Bioorg Med Chem Lett 2008; 18: 4688-4691
    CrossrefPubMedSearch in Google Scholar
  • 16 Li F, Awale S, Zhang H, Tezuka Y, Esumi H, Kadota S. Chemical constituents of propolis from Myanmar and their preferential cytotoxicity against a human pancreatic cancer cell line. J Nat Prod 2009; 72: 1283-1287
    CrossrefPubMedSearch in Google Scholar
  • 17 Li F, Awale S, Tezuka Y, Esumi H, Kadota S. Study on the constituents of Mexican propolis and their cytotoxic activity against PANC-1 human pancreatic cancer cells. J Nat Prod 2010; 73: 623-627
    CrossrefPubMedSearch in Google Scholar
  • 18 Chinese Pharmacopoeia Commission. Pharmacopoeia of the Peopleʼs Republic of China. Beijing: Chemical Industry Press; 2005
    Search in Google Scholar
  • 19 Qian GS, Wang Q, Leung KS, Qin Y, Zhao Z, Jiang ZH. Quality assessment of Rhizoma et Radix Notopterygii by HPTLC and HPLC fingerprinting and HPLC quantitative analysis. J Pharm Biomed Anal 2007; 44: 812-817
    CrossrefPubMedSearch in Google Scholar
  • 20 Zschocke S, Lehner M, Bauer R. 5-Lipoxygenase and cyclooxygenase inhibitory active constituents from Qianghuo (Notopterygium incisum). Planta Med 1997; 63: 203-206
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Yang XW, Gu ZM, Wang BX, Hattori M, Namba T. Comparison of anti-lipid peroxidative effects of the underground parts of Notopterygium incisum and N. forbesii in mice. Planta Med 1991; 57: 399-402
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Okuyama E, Nishimura S, Ohmori S, Ozaki Y, Satake M, Yamazaki M. Analgesic component of Notopterygium incisum Ting. Chem Pharm Bull (Tokyo) 1993; 41: 926-929
    CrossrefPubMedSearch in Google Scholar
  • 23 Wang X, Jia W, Zhao A. Anti-influenza agents from plants and traditional Chinese medicine. Phytother Res 2006; 20: 335-341
    CrossrefPubMedSearch in Google Scholar
  • 24 Qi J, Ojika M, Sakagami Y. Differentiation in a rat PC12 cell line induced by ostruthin and (−)-bornyl ferulate, constituents of a Chinese herbal medicine. Biosci Biotechnol Biochem 1999; 63: 1501-1502
    CrossrefPubMedSearch in Google Scholar
  • 25 Wu SB, Pang F, Wen Y, Zhang HF, Zhao Z, Hu JF. Antiproliferative and apoptotic activities of linear furocoumarins from Notopterygium incisum on cancer cell lines. Planta Med 2010; 76: 82-85
    Thieme ConnectPubMedSearch in Google Scholar
  • 26 Ribble D, Goldstein NB, Norris DA, Shellman YG. A simple technique for quantifying apoptosis in 96-well plates. BMC Biotechnol 2005; 5: 12
    CrossrefPubMedSearch in Google Scholar