Carcinostatic effects of diverse ascorbate derivatives in comparison with aliphatic chain moiety structures: Promotion by combined hyperthermia and reduced cytotoxicity to normal cells

Asada,Ryoko; Kageyama,Katsuhiro; Tanaka,Hiroshi; Kimura,Masatugu; Saitoh,Yasukazu; Miwa,Nobuhiko

doi:10.3892/ol.2012.615

May 2012 Volume 3 Issue 5

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May 2012 Volume 3 Issue 5

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Article

Carcinostatic effects of diverse ascorbate derivatives in comparison with aliphatic chain moiety structures: Promotion by combined hyperthermia and reduced cytotoxicity to normal cells

Authors:
- Ryoko Asada
- Katsuhiro Kageyama
- Hiroshi Tanaka
- Masatugu Kimura
- Yasukazu Saitoh
- Nobuhiko Miwa
View Affiliations / Copyright

Affiliations: Osaka Butsuryo College, Sakai, Osaka 593-8328, Japan, Faculty of Health Sciences, Butsuryo College of Osaka, Sakai, Osaka 593-8324, Japan, Radioisotope Center, Osaka City University, Abeno-Ku, Osaka 545-8585, Japan, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Hiroshima 727-0023, Japan
Pages: 1042-1046
|
Published online on: February 22, 2012

https://doi.org/10.3892/ol.2012.615
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Abstract

In this study, using human tongue squamous carcinoma cells (HSC-4) carcinostatic activity was compared for diverse L-ascorbic acid (Asc) derivatives, including the ‘straight-C16-chain types’, 6-O-palmitoyl-Asc (A6-P) and Asc-2-phosphate-6-O-palmitate sodium salt (APPS), as well as the ‘branched-C16-chain types’, Asc-2‑phosphate‑6‑O‑(2'‑hexyl)decanoate (APHD), an isomer of APPS, and Asc-2,3,5,6‑O‑tetra‑(2'-hexyl)decanoate (VCIP). The order of magnitude of the carcinostatic effects at 37˚C was: APPS>A6-P = APHD>VCIP and at 42˚C was APPS = A6-P>APHD>VCIP. Therefore, the two straight‑C16‑chain derivatives, APPS and A6-P, had a greater effect compared to the two branched-C16-chain Asc derivatives, which are considered to have more difficulty with ‘orientation along cell-membrane-glycerolipid direction’. APPS-treated HCS-4 cells were observed for a decrease in cell number, cell shrinkage, pycnosis indicative of apoptosis and cell deformation. The order of cytotoxicity for the normal human dermal fibroblasts (OUMS-36) at 37˚C was: A6-P (50% inhibitory concentration: 150-300 µM)>APHD (450‑600 µM)>>Asc = APPS (800-1000 µM). Accordingly, APHD was more cytotoxic than APPS, since the straight‑C16‑chain type, which was eliminated after the enzymatic esterolysis of APPS, is metabolized via the ‘fatty acid β-oxidation cycle’ more efficiently in normal cells. Thus, APPS had a greater advantage over APHD, A6-P and VCIP in terms of carcinostatic effects at 37˚C, carcinostasis promotion at 42˚C and a decrease of cytotoxicity to normal cells. This observation suggests a marked potential for aliphatic chain‑moiety structures as anticancer agents, due to their cancer-selective carcinostasis and combined efficacy with hyperthermia, without causing side effects.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Carcinostatic effects of diverse ascorbate derivatives in comparison with aliphatic chain moiety structures: Promotion by combined hyperthermia and reduced cytotoxicity to normal cells

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