Anti-tumor effect of vitamin A and D on head and neck squamous cell carcinoma.
OBJECTIVE
Vitamin A and D(3) have a very strong differentiation induction effect.


METHODS
We examined the anti tumor effect on head and neck squamous cell carcinoma (HNSCC) by treatment with several vitamins having strong differentiation induction effects in vitro.


METHODS
We used KB cell that an oral floor squamous cell carcinoma, vitamins as all-trans retinoic acid (ATRA), 4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid (TAC-101), 1alpha,25(OH)(2)D(3) (calcitriol) and 22-oxa-1,25-(OH)(2)D(3) (OCT). We determined receptors of vitamin A and D(3) using RT-PCR. Furthermore, we investigated the proliferation of tumor cells in concentration dependency using [3H]TdR uptake method, apoptosis and apoptosis related factors using TUNEL method and real-time PCR, cell cycle changes using flow cytometry, changing of the sensitivity of using MTT method, cytokine production and the angiogenesis factor using ELISA, by treatment with these vitamins.


RESULTS
The deficit of RAR-beta was found in the KB cell. Each vitamin suppressed the cell proliferation, induced apoptosis, and cell cycle arrest, upregulated sensitivity of the chemotherapeutics drugs and downregulated several angiogenesis factors and an apoptotic factor; survivin.


CONCLUSIONS
These results support the idea that vitamin A, D(3) and their derivatives are useful for preventing and/or treating patients with HNSCC.
Satake
Kenichi
K
Department of Otolaryngology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, 236-0004, Yokohama, Japan. ken49@med.yokohama-cu.ac.jp
Takagi
Emi
E
Ishii
Akiko
A
Kato
Yasumasa
Y
Imagawa
Yukari
Y
Kimura
Yuu
Y
Tsukuda
Mamoru
M
D043925:Angiogenesis Inducing Agents / Q000032:analysis; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000517:prevention & control; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000032:analysis; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D020287:In Situ Nick-End Labeling; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use; D014801:Vitamin A / Q000494:pharmacology / Q000627:therapeutic use*; D014807:Vitamin D / Q000494:pharmacology / Q000627:therapeutic use*
D043925:Angiogenesis Inducing Agents; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D016207:Cytokines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014801:Vitamin A; D014807:Vitamin D; D014212:Tretinoin; D002117:Calcitriol; C051883:maxacalcitol; D002945:Cisplatin; D005472:Fluorouracil