OPEN Foundation

Harmines inhibit cancer cell growth through coordinated activation of apoptosis and inhibition of autophagy

Share This Post

Share on facebook
Share on linkedin
Share on twitter
Share on email

Abstract

Harmine and its analogs have long been considered as anticancer agents. In vitro analyses suggested that intercalating DNA or inhibiting topoisomerase might contribute to the cytotoxic effect of this class of compound. However, this idea has not been rigorously tested in intact cells. By synthesizing novel derivatives, here we demonstrate that harmines did not activate the DNA damage response, a cellular signaling commonly induced by agents that intercalate DNA or inhibit topoisomerase. These findings suggest that mechanisms other than DNA intercalating or topoisomerase inhibiting contribute to the toxicity of harmines in vivo. Using a novel N2-benzyl and N9-arylated alkyl compound 10f that has good solubility and stability as the model, we show that harmines strongly inhibited the growth of cancer cells originated from breast, lung, bone and pancreas, but not that of normal fibroblasts. We further show that 10f induced apoptosis and inhibited autophagy in a dose and time-dependent manner. An apoptosis inhibitor suppressed 10f-induced cell death. Together, our results reveal previously unidentified insights into the anticancer mechanism of harmines, supporting future development of this compound class in the treatment of human cancers.
Geng, X., Ren, Y., Wang, F., Tian, D., Yao, X., Zhang, Y., & Tang, J. (2018). Harmines inhibit cancer cell growth through coordinated activation of apoptosis and inhibition of autophagy. Biochemical and biophysical research communications498(1), 99-104. 10.1016/j.bbrc.2018.02.205
Link to full text

OPEN Foundation

INTERESTED IN PSYCHEDELIC RESEARCH AND THERAPIES?

Subscribe to the OPEN Foundation’s newsletter to stay in the loop, hear about our events, and become a part of a community dedicated to advancing psychedelics.

By clicking subscribe, I confirm to receive emails from the OPEN Foundation and agree with its privacy policy.