Tocotrienol-adjuvanted dendritic cells inhibit tumor growth and metastasis: a murine model of breast cancer.
Tocotrienol-rich fraction (TRF) from palm oil is reported to possess anti-cancer and immune-enhancing effects. In this study, TRF supplementation was used as an adjuvant to enhance the anti-cancer effects of dendritic cells (DC)-based cancer vaccine in a syngeneic mouse model of breast cancer. Female BALB/c mice were inoculated with 4T1 cells in mammary pad to induce tumor. When the tumor was palpable, the mice in the experimental groups were injected subcutaneously with DC-pulsed with tumor lysate (TL) from 4T1 cells (DC+TL) once a week for three weeks and fed daily with 1 mg TRF or vehicle. Control mice received unpulsed DC and were fed with vehicle. The combined therapy of using DC+TL injections and TRF supplementation (DC+TL+TRF) inhibited (p<0.05) tumor growth and metastasis. Splenocytes from the DC+TL+TRF group cultured with mitomycin-C (MMC)-treated 4T1 cells produced higher (p<0.05) levels of IFN-γ and IL-12. The cytotoxic T-lymphocyte (CTL) assay also showed enhanced tumor-specific killing (p<0.05) by CD8(+) T-lymphocytes isolated from mice in the DC+TL+TRF group. This study shows that TRF has the potential to be used as an adjuvant to enhance effectiveness of DC-based vaccines.
Pathology Division, Faculty of Medicine and Health, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia ; Nutrition Unit, Malaysian Palm Oil Board, Bandar Baru Bangi, Selangor, Malaysia.
Sitti Rahma
SR
Abdul Hafid
Srikumar
S
Chakravarthi
Kalanithi
K
Nesaretnam
Ammu Kutty
AK
Radhakrishnan
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008325:Mammary Neoplasms, Experimental; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D024508:Tocotrienols / Q000008:administration & dosage*; D047368:Tumor Burden / Q000187:drug effects; D000097802:CD83 Antigen
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000972:Antineoplastic Agents, Phytogenic; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015415:Biomarkers; D019013:CD40 Antigens; D007136:Immunoglobulins; D007371:Interferon-gamma; D018664:Interleukin-12; D008562:Membrane Glycoproteins; D024508:Tocotrienols; D000097802:CD83 Antigen