Combination of apigenin treatment with therapeutic HPV DNA vaccination generates enhanced therapeutic antitumor effects.

Abstract

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.

CONCLUSION:

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.

• Authors: Chi-Mu Chuang, Archana Monie, Annie Wu, Chien-Fu Hung
• Journal: Journal of biomedical science (J Biomed Sci) Vol. 16 Pg. 49 (May 27 2009) ISSN: 1423-0127 [Electronic] England
• PMID: 19473507 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• HSP70 Heat-Shock Proteins
• Oncogene Proteins, Viral
• Papillomavirus E7 Proteins
• Papillomavirus Vaccines
• Vaccines, DNA
• oncogene protein E7, Human papillomavirus type 16
• Apigenin

Topics

• Animals
• Antigens, Neoplasm (metabolism)
• Antineoplastic Agents (administration & dosage)
• Apigenin (therapeutic use)
• Apoptosis
• Combined Modality Therapy (methods)
• Female
• HSP70 Heat-Shock Proteins (metabolism)
• Humans
• Immunotherapy (methods)
• Mice
• Mice, Inbred C57BL
• Oncogene Proteins, Viral (genetics)
• Papillomavirus E7 Proteins
• Papillomavirus Vaccines (metabolism)
• Vaccines, DNA (therapeutic use)