Chemo-immunotherapy using saffron and its ingredients followed by E7-NT (gp96) DNA vaccine generates different anti-tumor effects against tumors expressing the E7 protein of human papillomavirus.
Saffron and its components have been suggested as promising candidates for cancer prevention. Carotenoids and monoterpene aldehydes are two potent ingredients of saffron. The goal of the current study was to investigate the anti-tumor effect of chemo-immunotherapy using saffron and its ingredients followed by E7-NT (gp96) DNA vaccine against tumors expressing the E7 protein of human papillomavirus. The in vitro cytotoxic and apoptotic effects of aqueous saffron extract and its components were evaluated in malignant TC-1 and non-malignant COS-7 cell lines. Then, multimodality treatments using E7-NT (gp96) DNA vaccine combined with saffron extract and its ingredients as well as single-modality treatments were tested for their efficacy in inhibiting large and bulky tumor growth. Saffron and its components exerted a considerable anti-tumor effect through prevention of cell growth and stimulation of programmed cell death. Furthermore, 100 % of mice treated with crocin were tumor-free, in contrast to DNA vaccine alone (~66.7 %) and DNA + crocin (~33.3 %) indicating the high potency of crocin as a chemotherapeutic agent. Interestingly, the multimodality treatment using DNA vaccine along with picrocrocin augmented the anti-tumor effects of picrocrocin. Thus, the combination of DNA vaccine with saffron extract and crocin at certain concentrations did not potentiate protective and therapeutic effects compared to mono-therapies for the control of TC-1 tumors.
Department of Hepatitis and AIDs, Pasteur Institute of Iran, Tehran, Iran.
Afshin
A
Khavari
Azam
A
Bolhassani
Fatemeh
F
Alizadeh
S Zahra
SZ
Bathaie
Prabha
P
Balaram
Elnaz
E
Agi
Rouhollah
R
Vahabpour
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D019556:COS Cells; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002338:Carotenoids / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003131:Combined Modality Therapy; D027622:Crocus / Q000737:chemistry*; D053138:Cyclohexenes / Q000627:therapeutic use*; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy / Q000517:prevention & control / Q000628:therapy*; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000276:immunology / Q000627:therapeutic use*; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000627:therapeutic use; D011094:Polyethyleneimine / Q000494:pharmacology; D013729:Terpenes / Q000627:therapeutic use*; D014170:Transformation, Genetic; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D053138:Cyclohexenes; D005960:Glucosides; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D010936:Plant Extracts; D013729:Terpenes; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D002338:Carotenoids; C029036:crocin; D011094:Polyethyleneimine; C087962:picrocrocin