title: Activity of Artemisia annua and artemisinin derivatives, in prostate carcinoma.
abstract: BACKGROUND
  Artemisia annua L, artemisinin and artesunate reveal profound activity not only against malaria, but also against cancer in vivo and clinical trials. Longitudinal observations on the efficacy of A. annua in patients are, however missing as of yet.
  
  
  METHODS
  Clinical diagnosis was performed by imaging techniques (MRT, scintigraphy, SPECT/CT) and blood examinations of standard parameters from clinical chemistry. Immunohistochemistry of formalin-fixed, paraffin-embedded tumor material was performed to determine the expression of several biomarkers (cycloxygenase-2 (COX2), epidermal growth factor receptor (EGFR), glutathione S-transferase P1 (GSTP1), Ki-67, MYC, oxidized low density lipoprotein (lectin-like) receptor 1 (LOX1), p53, P-glycoprotein, transferrin receptor (TFR, CD71), vascular endothelial growth factor (VEGF), von Willebrand factor (CD31)). The immunohistochemical expression has been compared with the microarray-based mRNA expression of these markers in two prostate carcinoma cell lines (PC-3, DU-145).
  
  
  RESULTS
  A patient with prostate carcinoma (pT3bN1M1, Gleason score 8 (4+4)) presented with a prostate specific antigen (PSA) level >800 µg/l. After short-term treatment with bacalitumide (50 mg/d for 14 days) and long-term oral treatment with A. annua capsules (continuously 5 × 50 mg/d), the PSA level dropped down to 0.98 µg/l. MRT, scintigraphy and SPECT/CT verified tumor remission. Seven months later, PSA and ostase levels increased, indicating tumor recurrence and skeletal metastases. Substituting A. annua capsules by artesunate injections (2 × 150 mg twice weekly i.v.) did not prohibit tumor recurrence. PSA and ostase levels rose to 1245 µg/l and 434 U/l, respectively, and MRT revealed progressive skeletal metastases, indicating that the tumor acquired resistance. The high expression of MYC, TFR, and VEGFC in the patient biopsy corresponded with high expression of these markers in the artemisinin-sensitive PC-3 cells compared to artemisinin-resistant DU-145 cells.
  
  
  CONCLUSIONS
  Long-term treatment with A. annua capsules combined with short-term bicalitumide treatment resulted in considerable regression of advanced metastasized prostate carcinoma. Controlled clinical trials are required to evaluate the clinical benefit of A. annua in prostate cancer.
authors.affiliation: Practice for Naturopathy, 29499 Zernien, Germany.
authors.forename: Friedrich-Wilhelm
authors.initials: FW
authors.lastname: Michaelsen
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Mohamed E M
authors.initials: ME
authors.lastname: Saeed
authors.affiliation: Clinic for General Medicine, 29456 Hitzacker, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schwarzkopf
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany. Electronic address: efferth@uni-mainz.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D000369:Aged, 80 and over; D031172:Artemisia annua / Q000737:chemistry*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000556:secondary; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D037621:Artemisinins; D014408:Biomarkers, Tumor; D000077332:Artesunate; C031327:artemisinin; D017430:Prostate-Specific Antigen
keywords: Asteraceae; Drug resistance; PSA, Sesquiterpene; Tumor imaging; Tumor marker