Current
cancer treatments of solid tumours such as
chemotherapy and
radiotherapy, have yet to produce effective therapeutic results due to non-specific targeting. This has led to many complications, such as toxicities in
cancer patients. The ability of natural compounds in inducing programmed cell death (apoptosis), a process dysregulated in
cancer cells, has been extensively studied in recent studies. This study assessed the anti-proliferative activity of
violacein in a number of human
cancer cell lines under normal and hypoxic conditions. Furthermore, we investigated its effects in a tumour‑bearing subcutaneous mouse model. We also examined the ability of a tumour‑targeting Salmonella strain to produce
violacein for local delivery within the tumour microenvironment. The results showed that
hypoxia significantly increased the cytotoxic effects of
violacein. The most significant reduction in the IC50 was in the HT29 (12.6-fold) and HCT116 (4.8-fold)
colon cancer cell lines, HN5 head and neck
squamous carcinoma cell line (6.5-fold), and MCF-7
breast ductal carcinoma cell line (4-fold). Among the cell lines tested for active
caspase-3/7 activity,
violacein only increased
caspase-3/7 activity in the A549 non-small
lung cancer cell line. In vivo efficacy of
violacein showed that HN5 tumour‑bearing mice had regressed tumours during the treatment period and survival increased. The results also showed that transfer of the
violacein biosynthetic cluster into the oncolytic strain
VNP20009 of Salmonella resulted in the production of active
violacein, suggesting targeted delivery of
violacein by
VNP20009. Taken together, our study has shown that
hypoxia synergises the effects of
violacein and the results from the in vivo administration of
violacein require further investigation of
violacein as an anticancer chemotherapeutic.