Combination of apigenin treatment with therapeutic HPV DNA vaccination generates enhanced therapeutic antitumor effects.
BACKGROUND
It is important to develop innovative therapies for advanced stage cancers in addition to the conventional therapies including chemotherapy, radiation and surgery. Antigen-specific immunotherapy has emerged as a novel alternate therapy for advanced stage cancers, which may be employed in conjunction with conventional therapies.


METHODS
In the current study, we tested the effect of treatment with the chemotherapeutic agent, apigenin in combination with DNA vaccines encoding the HPV-16 E7 antigen linked to heat shock protein 70 (HSP70) in the control of the E7-expressing tumor, TC-1.


RESULTS
We observed that treatment with apigenin rendered the TC-1 tumor cells more susceptible to lysis by E7-specific cytotoxic CD8+ T cells. Furthermore, treatment of TC-1 tumor cells with apigenin was found to enhance apoptotic tumor cell death in vitro in a dose-dependant manner. We showed that TC-1 tumor-bearing mice treated with apigenin combined with E7-HSP70 DNA generate highest frequency of primary and memory E7-specific CD8+ T cells, leading to potent therapeutic anti-tumor effects against E7-expressing tumors.


CONCLUSIONS
Thus, apigenin represents a promising chemotherapeutic agent, which may be used in combination with immunotherapy for the treatment of advanced stage cancers. The clinical implications of the current strategy are discussed.
Chuang
Chi-Mu
CM
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. cmjuang@yahoo.com.tw
Monie
Archana
A
Wu
Annie
A
Hung
Chien-Fu
CF
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D047310:Apigenin / Q000627:therapeutic use*; D017209:Apoptosis; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines / Q000378:metabolism; D019444:Vaccines, DNA / Q000627:therapeutic use
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D047310:Apigenin