Loss of an ABC transporter in Arabidopsis thaliana confers hypersensitivity to the anti-cancer drug bleomycin.

Bleomycin (BLM) is used as an anti-cancer drug clinically. However, some cancer cells are resistant to BLM, which limits the usage of BLM in chemotherapy. But the underlying mechanism of such resistance is poorly understood. Here we show that the ATP binding cassette (ABC) transporter ABCC3 is required for the BLM-resistance in Arabidopsis. In a genetic screen for ddrm (DNA damage response mutants), we found that loss of ABCC3 confers the hypersensitivity to BLM. In contrast, overexpression of ABCC3 enhances the resistance to BLM. We further found that the expression of ABCC3 is induced by BLM, which is dependent on the protein kinase ATM and the transcription factor SOG1, two master regulators of DNA damage response. Our study revealed that the ABC transporter contributes to BLM-resistance, indicating that the combination of ABC transporter inhibitors and BLM may enhance the efficacy of BLM in cancer therapy.