Apoptotic chemotherapies

Mutations derange growth regulations of cancer cells. They can also make the cells more subject to apoptosis. We have investigated two drugs that produce specific apoptotic chemotherapeutic mechanisms that cause tumor shrinkage in mice without deleterious side effects.

The small natural product b-lapachone is specifically apoptotic to a variety of cancer cells. It synergizes strongly with taxol. It seems to have several mechanisms of lethality depending on the tumor type and the drug concentration. One mechanism is to elevate the major S-phase transcription factor E2F-1, to an apoptotic concentration [1]. It is now in clinical trial.

Tumor cells often mutate to apoptosis resistance; for example, by inactivating the p53 protein. We have reported that Go6976, a kinase inhibitory small molecule, can decrease activation of the anti-apoptotic transcription factor NF-κB [2].

These two novel therapies thus specifically cause cancer cell apoptosis; one by increasing an apoptotic factor, and the other restoring apoptosis by decreasing an anti-apoptotic factor.