ection for 4 weeks compared with control animals. Furthermore, TSA did not cause any measurable toxicity in doses of up to 5 mg/kg (≒16,500 nM) \[[@R30]\]. Due to the direct contact of TSA to tumor cells *in vitro*, we tested the effect of TSA on HeLa cells from 100 nM to 1,000 nM for 48 h-incubation (Figure [1](#F1){ref-type="fig"}). So, we thought that these concentrations are physiologically or clinically reasonable to see whether tumor cell death might be modified by TSA treatment.

In the beginning of our study, we tested the effect of TSA as one of anticancer agents on HeLa cell death. As shown in Figure [1A](#F1){ref-type="fig"}, when tumor cells were incubated with TSA for 48 h, we observed that tumor cell death was significantly increased from 300 nM which is the lowest concentration under our experimental condition. TSA-induced tumor cell death was time-dependently increased and little changes were detected by the incubation with 300 nM TSA for less than 12 h \[[@R27]\]. Then, we are interesting to see what is happened in tumor cell death by the treatment with 300 nM or less concentration of TSA for most experiments in our study.

Anticancer efficacy is reduced by HIF-1α overexpression or hypoxic conditions, which can lead to drug resistance \[[@R10]--[@R12]\]. It is also possible for drug resistance to be induced by HIF-1α acetylation. HDAC4 regulates HIF-1α acetylation, which can be increased by HDAC4 short hairpin RNA (shRNA) and decreased by HDAC4 overexpression. In contrast, HIF-1α protein stability is inhibited by HDAC4 shRNA, which leads to a decrease in both the HIF-1α transcriptional activity and target gene expression \[[@R17]\]. Whereas no changes were shown in HIF-1α stability by HDAC1 or HDAC3 shRNA \[[@R17]\], HDAC1 and HDAC3 positively regulate HIF-1α stability *via* directly binding to the ODD domain of HIF-1α \[[@R21]\]. HDAC1 also regulates VEGF expression in normal keratinocytes (HaCaT cells) \[[@R31]\]. Endogenous HIF-1α increase by TSA treatment could hamper antitumor eff