A Theoretical Model for the Hormetic Dose-response Curve for Anticancer Agents.
In the present article, we quantitatively evaluated the dose-response relationship of hormetic reactions of anticancer agents in vitro. Serial dilutions of gemcitabine, cisplatin, 5-fluorouracil, vinorelbine, and paclitaxel were administered to the A549 non-small-cell lung cancer cell line. The bi-phasic sigmoidal curve with hormetic and cytotoxic effects is given by the formula y=(a-b/(1+exp(c(*)log(x)-d)))/(1+exp(e(*)log(x)-f)), that was used to perform a non-linear least square regression. The dose-responses of the five anticancer agents were fitted to this equation. Gemcitabine and 5-fluorouracil, which had the lowest ED50 for their hormetic reaction, had the most pronounced promotive effects out of the five anticancer agents tested. The hormetic reaction progressed exponentially with culturing time. Our theoretical model will be useful in predicting how hormetic reactions affect patients with malignant tumors.
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan yositatu@wakayama-med.ac.jp.
Tatsuya
T
Yoshimasu
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Takuya
T
Ohashi
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Shoji
S
Oura
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Yozo
Y
Kokawa
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Mitsumasa
M
Kawago
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Yoshimitsu
Y
Hirai
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Miwako
M
Miyasaka
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Haruka
H
Nishiguchi
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Sayoko
S
Kawashima
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Yumi
Y
Yata
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Mariko
M
Honda
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Takahiro
T
Fujimoto
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Yoshitaka
Y
Okamura
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D059165:Hormesis / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008962:Models, Theoretical; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents
Hormesis; chemotherapy; lung cancer