Chloroquine is one possible answer. Chloroquine has its origin in 1934 when Hans Andersag synthesized it at I.G. Farbenindustrie in Wuppertal-Elberfeld, Germany (by the way, the city where I grew up) as a therapeutic for malaria. Nowadays, many malaria parasites are resistant.
In addition to malaria treatment, Chloroquine is used for therapy of rheumatoid arthritis. In cell culture lab, it helps to improve transfection efficiency and gets more and more into the focus of cancer treatment. Used as sensitizer for radiotherapy and chemotherapy, I wonder about the mechanism behind it? What does Chloroquine do that makes it an “all purpose weapon”?
It was in 1964 that a Japanese group showed that Chloroquine can be used to treat malignant bladder tumors. In 2018, 54 years later, in the paper of Chen et al Chloroquine has been used as a one-time treatment on bladder cancer cell lines, to understand a bit of the mechanism behind it.
They checked the lysosomes and found Chloroquine to induce lysosomal membrane permeability that enhances apoptosis in a time- and dose-dependent manner via activation of Caspase-3. Following the above link, please find also live cell imaging videos of the treated cells recorded by the CytoSMARTTM System.
This is why I am a big fan of live cell imaging. Time courses and focusing on individual cells can sometimes give more insight rather than investigating the average of a cell population at only one or two time points.
Also in 2018 a group from China investigated the effect of Chloroquine on the anti-tumor immune response of macrophages.
It becomes clear that we are not at the point of understanding the whole story of what this drug is doing. It’s hopeful and scary at the same time, isn’t it?
Written by Isabella
Scientific Support Specialist, Lonza Pharma-Bioscience Solutions at Lonza