Many anti-cancer substances have been shown to cause paraptosis in a large range of human cancer cells. This includes several compounds derived from natural sources as well as metal complexes. The use of naturally derived compounds to treat cancer can provide a way to avoid many of the harmful side effects of traditional chemotherapy. Paraptosis is also an area of interest for cancer research as a way to treat apoptosis resistant cancers.
Paclitaxel, commonly distributed under the trade name Taxol, is a cancer drug used for the treatment of breast and ovarian cancers. At high concentrations (70 μM), one study showed it to induce a paraptosis-like cell death, and could be an important mechanism for treating apoptosis-resistant cancers.
Researchers have reported finding that γ-Tocotrienol, a form of vitamin E derived from palm oil, induced paraptosis-like cell death in colon cancer cells. Along with inducing paraptosis, γ-tocotrienol also suppressed the Wnt signaling pathway, which plays a role in tumor development. The combination of these two features could provide a novel mechanism for treating colon cancer.
Honokiol, a compound derived from Magnolia officinalis, can induce paraptosis in human leukemia cells. In the NB4 cell line, paraptosis was the primary method of cell death. In K562 cells, apoptosis was the primary mechanism, with paraptosis occasionally found. Researchers stated that this suggests that leukemia cell death can be induced by multiple pathways.
In one experiment a phosphine copper(I) complex caused paraptosis in colon cancer cells by inducing endoplasmic reticulum stress. Another copper complex, the A0 thioxotriazole copper (II) complex, also caused paraptosis in HT1080 fibrosarcoma cells via endoplasmic reticulum stress and cytoplasmic vacuolization. Along with cytotoxic effects such as an increase in oxidized glutathione and prevention of proteasome activity, A0 prevented the activity of caspase-3, which may inhibit apoptosis and cause the cells to die via paraptosis.