Steroid hormones induce HMG1 overexpression and sensitize breast cancer cells to cisplatin and carboplatin.
Cisplatin is an anticancer drug that has enjoyed remarkable success against testicular tumors, but dose limiting side-effects have limited its application against a broader range of cancers. Previous studies have shown that high-mobility group (HMG) domain proteins such as HMG1 sensitize cells to cisplatin by shielding its major DNA adducts from nucleotide excision repair. Estrogen treatment increases HMG1 mRNA levels in breast cancer MCF-7 cells. Herein, we describe that treatment of human cancer cells having steroid hormone receptors with the appropriate hormone, estrogen and/or progesterone, significantly increases the potency of cisplatin and its analogue carboplatin by causing the overexpression of HMG1. These findings suggest that the proper combination of these drugs, which are already approved by the Food and Drug Administration, could have potential benefit in treating tumors such as ovarian or breast that carry the hormone receptors.
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Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Liang
C H
CH
Lippard
S J
SJ
D000230:Adenocarcinoma / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D016190:Carboplatin / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D018736:DNA Adducts; D004273:DNA, Neoplasm / Q000032:analysis; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D024243:HMGB1 Protein; D006609:High Mobility Group Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D011374:Progesterone / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018736:DNA Adducts; D004273:DNA, Neoplasm; D004967:Estrogens; D024243:HMGB1 Protein; D006609:High Mobility Group Proteins; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone; D016190:Carboplatin; D002945:Cisplatin