Preferential Induction of CYP1A1 over CYP1B1 in Human Breast Cancer MCF-7 Cells after Exposure to Berberine

Abstract

Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to DNA modification caused by derivatives formed during metabolism. 17β-estradiol (E 2 ), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol (2-OH E 2 ) and 4-hydroxyestradiol (4-OH E 2 ) through the action of cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that 2-OH E 2 has putative protective effects, while 4-OH E 2 is genotoxic and has potent carcinogenic activity. Thus, the ratio of 2-OH E 2 /4-OH E 2 is a critical determinant of the toxicity of E 2 in mammary cells. In the present study, we investigated the effects of berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16~ to 52~fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect E 2 metabolism in a more protective pathway in breast cancer MCF-7 cells.

CXCR4 promotes cisplatin-resistance of non-small cell lung cancer in a CYP1B1-dependent manner

“…CYP1B1 belongs to cytochrome p450 family, which is a multi-gene family of enzymes implicated in the metabolism of a diverse range of xenobiotics and endogenous compounds (24). Several researchers have proposed interesting concepts, in explaining the mechanisms of CYP1B1 induced cytotoxic effect reduction of chemotherapeutic drug (20,21,23,25), as other have mainly focused on CYP1B1 polymorphism in cancer process (22,32,33). Of particular interest, Patel et al reported that CYP1B1 may be regulated by cytokines, as interleukin-6 was observed to mediate of CYP1B1 upregulation via DNA methylation in colorectal cancer (34).…”

“…CXCR4 promotes cisplatin resistance through upregulation of CYP1B1. Increasing evidence has shown that many cytotoxic drugs are metabolized by cytochrome p450 (CYP) enzymes (17)(18)(19)(20)(21)(22)(23)(24)(25), we therefore explored the correlation of CXCR4 with CYP-related molecules (CYP1A1, CYP1A2, CYP1B1, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, CYP3A4, CYP3A5, CYP3A7 and CYP3A43) by bioinformatics (Table II). Our results indicated a positive correlation between CXCR4 and CYP1B1 with r= 0.616 (P<0.0001) and r= 0.538 (P<0.0001) in GSE30219 and GSE41271 datasets, respectively ( Fig.…”

Correlation of Anticancer Effects of 12 Iranian Herbs on Human breast Adenocarcinoma cells with antioxidant Properties

“…19 Current therapies for breast cancer consist of surgery, radiation therapy and chemohormone therapy. However, these therapies are often ineffective.…”

The antioxidant and chemical properties of Berberis vulgaris and its cytotoxic effect on human breast carcinoma cells

“…Breast cancer is the most common malignancy in women both in the developed and the developing countries (Wen et al 2014). Its common treatments are surgery, radiation and chemo-hormone therapies.…”