title: Ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases.
abstract: Ocimum genus (a.k.a holy basil or tulsi) is a dietary herb used for its multiple beneficial pharmacologic properties including anti-cancer activity. Here we show that crude extract of Ocimum gratissimum (OG) and its hydrophobic and hydrophilic fractions (HB and HL) differentially inhibit breast cancer cell chemotaxis and chemoinvasion in vitro and retard tumor growth and temporal progression of MCF10ADCIS.com xenografts, a model of human breast comedo-ductal carcinoma in situ (comedo-DCIS). OG-induced inhibition of tumor growth was associated with decreases in basement membrane disintegration, angiogenesis and MMP-2 and MMP-9 activities as confirmed by in situ gelatin zymography and cleavage of galectin-3. There was also decrease in MMP-2 and MMP-9 activities in the conditioned media of OG-treated MCF10AT1 and MCF10AT1-EIII8 premalignant human breast cancer cells as compared with control. The MMP-2 and MMP-9 inhibitory activities of OG were verified in vitro using gelatin, a synthetic fluorogenic peptide and recombinant galectin-3 as MMP substrates. Mice fed on OG-supplemented drinking water showed no adverse effects compared with control. These data suggest that OG is non-toxic and that the anti-cancer therapeutic activity of OG may in part be contributed by its MMP inhibitory activity.
authors: Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA. makkerp@karmanos.org
authors: Pratima
authors: P
authors: Nangia-Makker
authors: Tirza
authors: T
authors: Raz
authors: Larry
authors: L
authors: Tait
authors: Malathy P V
authors: MP
authors: Shekhar
authors: Hong
authors: H
authors: Li
authors: Vitaly
authors: V
authors: Balan
authors: Hemanckur
authors: H
authors: Makker
authors: Rafael
authors: R
authors: Fridman
authors: Krishnarao
authors: K
authors: Maddipati
authors: Avraham
authors: A
authors: Raz
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D031339:Ocimum / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Breast Cancer; MMP; Ocimum gratissimum; Tumor progression
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