Anti-malarial helps kill drug-resistant lung cancer cells
doi:10.1038/nindia.2019.66 Published online 24 May 2019
Biologists have discovered that chloroquine, an anti-malarial drug, could help kill drug-resistant human lung cancer cells1. The anti-malarial drug helped kill the cancer cells by making them sensitive to paclitaxel, a commonly used anti-cancer drug.
This finding may pave the development of a novel therapy for drug-resistant lung cancer.
Lung cancer cells develop resistance to drugs such as paclitaxel by employing various mechanisms, including autophagy, a cellular process that degrades protein aggregates and damaged cellular organelles. Such degradation provides the cancer cells with nutrients, allowing them to proliferate.
Scientists from the University of Calcutta and the CSIR-Institute of Chemical Biology in Kolkata, India, aimed to starve the cancer cells to death by inhibiting autophagy. To do this, they pre-treated specific human lung cancer cells with chloroquine, which is known to stop autophagy. They then exposed these pre-treated cells to paclitaxel and compared them with only paclitaxel-treated lung cancer cells.
The researchers, led by Gopal Chakrabarti, found that the chloroquine pre-treatment increased the death of the cancer cells, with no signs of drug-resistance. The pre-treatment also lowered the levels of specific proteins that make cancer cells resist anti-cancer drugs.
The chloroquine pre-treatment blocked autophagy preventing the removal of damaged mitochondria, which is rich in reactive oxygen species (ROS). This increased the levels of ROS that killed the cancer cells through apoptosis, a process of controlled cell death.
Treating the cancer cells with an antioxidant reduced cell death to almost half, proving that the ROS were chiefly responsible for the cancer cells’ death.
1. Datta, S. et al. Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway. Apoptosis.24, 414-433 (2019)