Panax Ginseng - Thorne Research

ReviewPanax ginseng and Cancerapoptosis, including the cleavageof poly-ADP ribose polymerase(PARP); the up-regulationof Bax, Bid, p53, p21, andp27 proteins; and the decreasedexpression of c-myc and cyclinD, E and A kinases. 48-51,55-59 (Theinducing effects of P. ginseng inall these studies were abrogatedby inhibitors verifyingginsenoside action.)Figure 4. Regulation of the Apoptotic Pathways:The Extrinsic PathwayExtrinsic pathwayRb1 metabolitesInhibition ofProliferationThe proliferation phase,including tumor-cell migration,invasion, and metastasis, ismodulated by neurotransmittersand chemokines (Figure 6). 17 Theprotopanaxadiol metabolites ofP. ginseng have been shown toreduce catecholamine secretion through bindingto nicotinic receptors and blocking sodium influxthrough the receptors. 2 Catecholamines have beennoted as a chemo-attractant of breast carcinomacells 59 and as an activator for the migration of coloncarcinoma cells. 60 The therapeutic benefit ofP. ginseng in neurotransmission warrants furtherinvestigation.P. ginseng has also been noted to reducelung metastasis in two highly metastatic tumor celllines – colon 26-M3.1 and B16-BL6 melanoma;Rb2 inhibits their angiogenesis. 61 Rg3 inhibits theadhesion of tumor cells to extracellular matrix andbasement membrane components 62,63 and, despiteinhibiting metastasis, does not change the growthor vascularity of induced intestinal cancers. 64Rb1 and its metabolite (Compound K)have shown reduction in lung metastasis in miceinjected with Lewis lung carcinoma. CompoundK was found to be twice as effective as Rb1 andto have almost the same antimetastatic potentialas 5-fluorouracil (5-FU) – a chemotherapeuticagent. Because of the potential toxicity of 5-FU,Compound K may provide promising long-termtherapy, given its low toxicity – LD 50> 5g/kg. 65LRActivatesCaspase 3Bid = proapoptotic Bcl-2 family member; tBid = truncated Bid; AMPs = proapoptoticmitochondrial proteinsFrom: Sun SY, Hail N Jr, Lotan R. Apoptosis as a novel target for cancer chemoprevention.J Natl Cancer Inst 2004;96(9):662-72.LRPlasmamembraneCaspase 8 Propase 8EffectorcaspasesClassic pathwayBidCaspaseactivationApoptosistBidAMPsInner mitochondrialmembraneOuter mitochondrialmembraneFigure 5. Regulation of the ApoptoticPathways: The Intrinsic PathwayIntrinsic pathwayOuter mitochondrialmembraneBax, Bad, or BakBcl-2 or Bcl-X LApoptosisCaspaseactivationCaspaseactivationAMPsAMPsInner mitochondrialmembranePermeability transitionpore complexOuter mitochondrialmembrane fragmentAMPs = proapoptotic mitochondrial proteinsFrom: Sun SY, Hail N Jr, Lotan R. Apoptosis as a novel target forcancer chemoprevention. J Natl Cancer Inst 2004;96(9):662-72.Alternative Medicine Review ◆ Volume 9, Number 3 ◆ 2004 Page 265Copyright©2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission