title: Arum Palaestinum with isovanillin, linolenic acid and β-sitosterol inhibits prostate cancer spheroids and reduces the growth rate of prostate tumors in mice.
abstract: BACKGROUND
  Arum palaestinum is a plant commonly found in the Middle East that is ingested as an herbal remedy to fight cancer. However, no studies have examined the direct effect of the plant/plant extract on tumor growth in an animal model.
  
  
  METHODS
  Verified prostate cancer cells were plated as 3D spheroids to determine the effect of extract from boiled Arum Palaestinum Boiss roots. In addition, male NU/NU mice (8 weeks old) with xenograft tumors derived from the prostate cancer cell line were treated daily with 1000 mg/kg body weight gavage of the suspension GZ17. The tumor growth was measured repeatedly with calipers and the excised tumors were weighed at the termination of the 3 week study. Control mice (10 mice in each group) received vehicle in the same manner and volume.
  
  
  RESULTS
  The number of live prostate cancer cells declined in a dose/dependent manner with a 24 h exposure to the extract at doses of 0.015 to 6.25 mg/mL. A fortified version of the extract (referred to as GZ17) that contained higher levels of isovanillin, linolenic acid and β-sitosterol had a stronger effect on the cell death rate, shifting the percentage of dead cells from 30 % to 55 % at the highest dose while the vehicle control had no effect on cell numbers. When GZ17 was applied to non-cancer tissue, in this case, human islets, there was no cell death at doses that were toxic to treated cancer cells. Preliminary toxicity studies were conducted on rats using an up-down design, with no signs of toxic effect at the highest dose. NU/NU mice with xenograft prostate tumors treated with GZ17 had a dramatic inhibition of tumor progression, while tumors in the control group grew steadily through the 3 weeks. The rate of tumor volume increase was 73 mm(3)/day for the vehicle group and 24 mm(3)/day for the GZ17 treated mice. While there was a trend towards lower excised tumor weight at study termination in the GZ17 treatment group, there was no statistical difference.
  
  
  CONCLUSIONS
  Fortified Arum palaestinum Boiss caused a reduction in live cells within prostate cancer spheroids and blocked tumor growth in xenografted prostate tumors in mice without signs of toxicity.
authors.affiliation: Likarda, LLC, 2002 W. 39th Ave, Kansas City, KS, 66103, USA. ccole@likarda.com.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Cole
authors.affiliation: Genzada Pharmaceuticals, LLC, 205 S. Broadway, Sterling, KS, 67579, USA. thomas.burgoyne@jacam.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Burgoyne
authors.affiliation: Likarda, LLC, 2002 W. 39th Ave, Kansas City, KS, 66103, USA. annie.lee@rockhurst.edu.|Rockhurst University, 1100 Rockhurst Rd, Kansas City, MO, 64110, USA. annie.lee@rockhurst.edu.
authors.forename: Annie
authors.initials: A
authors.lastname: Lee
authors.affiliation: Likarda, LLC, 2002 W. 39th Ave, Kansas City, KS, 66103, USA. lbittel@kumc.edu.|University of Kansas Medical Center, MS 2002, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA. lbittel@kumc.edu.
authors.forename: Lisa
authors.initials: L
authors.lastname: Stehno-Bittel
authors.affiliation: Genzada Pharmaceuticals, LLC, 205 S. Broadway, Sterling, KS, 67579, USA. Gene.zaid@genzada.com.
authors.forename: Gene
authors.initials: G
authors.lastname: Zaid
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D031058:Arum / Q000737:chemistry*; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D012855:Sitosterols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D017962:alpha-Linolenic Acid / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001547:Benzaldehydes; D010936:Plant Extracts; D012855:Sitosterols; D017962:alpha-Linolenic Acid; C093382:isovanillin; C025473:gamma-sitosterol