Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Anticancer Activity of Continentalic Acid in B-Cell Lymphoma.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Basel, Switzerland : MDPI, c1995-
    • الموضوع:
      Antineoplastic Agents/*pharmacology ; Diterpenes/*pharmacology ; Lymphoma, B-Cell/*drug therapy; Apoptosis/drug effects ; Aralia/chemistry ; Lymphoma, B-Cell/metabolism ; Plant Extracts/pharmacology ; Plant Roots/chemistry ; Animals ; Cell Line, Tumor ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Republic of Korea
    • نبذة مختصرة :
      Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in vivo results suggest that the cytotoxic activities of continentalic acid, a major diterpene from A. continentalis extract, are specific towards cancer cells while leaving normal murine cells and tissues unharmed. Mechanistically, continentalic acid represses the expression of pro-survival Bcl-2 family members, such as Mcl-1 and Bcl-xL. It dissociates the mitochondrial membrane potential, leading to the stimulation of effector caspase 3/7 activities and, ultimately, cell death. Intriguingly, this agent therapeutically synergizes with roflumilast, a pan-PDE4 inhibitor that has been successfully repurposed for the treatment of aggressive B-cell malignancies in recent clinical tests. Our findings unveiled that A. continentalis extract and three of the plant's diterpenes exhibit anti-cancer activities. We also demonstrate the synergistic inhibitory effect of continentalic acid on the survival of B-lymphoma cells when combined with roflumilast. Taken in conjunction, continentalic acid may hold significant potential for the treatment of B-cell lymphoma.
    • References:
      Braz J Med Biol Res. 2013 Jan;46(1):71-78. (PMID: 23314342)
      Genes Genomics. 2020 May;42(5):543-551. (PMID: 32207045)
      Nature. 2000 Feb 3;403(6769):503-11. (PMID: 10676951)
      Onco Targets Ther. 2018 Oct 23;11:7301-7314. (PMID: 30425521)
      Sci Rep. 2018 Jul 12;8(1):10590. (PMID: 30002430)
      Genes Dev. 2012 Jan 15;26(2):120-5. (PMID: 22279045)
      Indian J Pharm Sci. 2015 Nov-Dec;77(6):792-5. (PMID: 26997711)
      BMC Complement Altern Med. 2019 Jan 8;19(1):11. (PMID: 30621666)
      Pharmacol Ther. 2019 Jun;198:59-67. (PMID: 30790641)
      Science. 2008 Mar 21;319(5870):1676-9. (PMID: 18323416)
      Arch Pharm Res. 2008 Sep;31(9):1172-8. (PMID: 18806961)
      Oncol Rep. 2020 Dec;44(6):2746-2756. (PMID: 33125144)
      Bioorg Med Chem. 2010 Feb 15;18(4):1724-35. (PMID: 20116261)
      Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824-7. (PMID: 6961453)
      Foods. 2020 Jan 01;9(1):. (PMID: 31906298)
      J Clin Oncol. 2003 Nov 1;21(21):3940-7. (PMID: 12975461)
      Leukemia. 2005 Jul;19(7):1248-52. (PMID: 15902294)
      Nature. 1983 Dec 22-1984 Jan 4;306(5945):760-5. (PMID: 6419122)
      Leukemia. 2002 Apr;16(4):444-54. (PMID: 11960321)
      Phytother Res. 2002 Jun;16(4):387-8. (PMID: 12112299)
      Leukemia. 2019 Dec;33(12):2912-2923. (PMID: 31138843)
      Blood. 1994 Jan 15;83(2):435-45. (PMID: 7506951)
      Antioxidants (Basel). 2020 May 04;9(5):. (PMID: 32375422)
      Biomaterials. 2012 Sep;33(26):6155-61. (PMID: 22682937)
      N Engl J Med. 2002 Jan 24;346(4):235-42. (PMID: 11807147)
      Lancet. 2017 Jul 15;390(10091):298-310. (PMID: 28153383)
      Nature. 2011 Feb 3;470(7332):115-9. (PMID: 21179087)
      Biomed Pharmacother. 2021 Jun;138:111411. (PMID: 33711550)
      Semin Hematol. 2010 Apr;47(2):115-23. (PMID: 20350658)
      Leukemia. 2012 Jun;26(6):1383-90. (PMID: 22189900)
      J Med Chem. 2007 Dec 27;50(26):6685-91. (PMID: 18038969)
      J Microbiol Biotechnol. 2021 Sep 26;31(11):. (PMID: 34584041)
      Pathology. 2018 Jan;50(1):74-87. (PMID: 29167021)
      Planta Med. 2019 Nov;85(16):1242-1252. (PMID: 31597167)
    • Grant Information:
      2020R1A2C1003388 National Research Foundation of Korea; 2020R1l1A2075060 National Research Foundation of Korea
    • Contributed Indexing:
      Keywords: Aralia continentalis; B-cell lymphoma; anti-cancer activities; diterpenes
    • الرقم المعرف:
      0 (Antineoplastic Agents)
      0 (Diterpenes)
      0 (Plant Extracts)
      0 (continentalic acid)
    • الموضوع:
      Date Created: 20211127 Date Completed: 20211207 Latest Revision: 20211214
    • الموضوع:
      20260130
    • الرقم المعرف:
      PMC8625780
    • الرقم المعرف:
      10.3390/molecules26226845
    • الرقم المعرف:
      34833935