Fig. 6: A proposed model illustrating that brusatol suppresses progestin metabolism and sensitizes precancerous/endometrial cancers to progestin. | Laboratory Investigation

Fig. 6: A proposed model illustrating that brusatol suppresses progestin metabolism and sensitizes precancerous/endometrial cancers to progestin.

From: Brusatol sensitizes endometrial hyperplasia and cancer to progestin by suppressing NRF2-TET1-AKR1C1-mediated progestin metabolism

Fig. 6: A proposed model illustrating that brusatol suppresses progestin metabolism and sensitizes precancerous/endometrial cancers to progestin.The alternative text for this image may have been generated using AI.

NRF2 binds to the AREs in the TET1 promoter region and enhances TET1 expression, which in turn facilitating AKR1C1 expression via hydroxymethylation modification. Furthermore, high levels of NRF2 enhance progestin metabolism by upregulating AKR1C1, which contributes to progestin resistance due to loss of drug function in progestin treatment. This kind of progestin resistance can be reversed by brusatol.

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