We have previously reported that
sodium 5,6-benzylidene-L-ascorbate (SBA) induced dramatic antitumor activity in inoperable
cancer patients, but induced only marginal
tumor specificity in vitro. Here the
tumor specificity and type of cell death induced by
benzaldehyde (BA), a degradation product of SBA, was investigated, using human tumor cell lines (
oral squamous cell carcinoma [OSCC],
glioblastoma,
myelogenous leukemia) and human normal oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast). BA showed much higher
tumor-specific cytotoxicity than SBA. BA induced the formation of autophagosomes, the destruction of mitochondrial structure and digestion of broken organelles, without any apparent induction of internucleosomal DNA fragmentation and
caspase activation in an OSCC cell line HSC-2, in a similar manner to SBA. However, pretreatment with
3-methyladenine or
bafilomycin A(1), autophagy inhibitors, did not completely rescue the cells from the cytotoxicity induced by BA. The study suggests that BA may play an important role in the induction of antitumor activity of SBA in vivo, although the autophagic phenotypes induced by BA may be involved in both cell death and survival.