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[Effect of 2-methoxyestradiol on proliferation and apoptosis of myeloma cell lines]
1Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China.
Abstract:
The objective was to explore the in vitro effects of growth inhibition and apoptosis induction of 2-methoxyestradiol (2ME2), an estrogen derivative, on seven myeloma cell lines NCI-H929, HS-sultan, KM3, SKO-007, CZ-1, U266 and LP-1and to observe its synergistic effects in combination with some other drugs, such as dexamethasone, As(2)O(3), thalidomide and zoledronic acid. Seven myeloma cell lines NCI-H929, HS-sultan, KM3, SKO-007, CZ-1, U266 and LP-1 were cultured at different concentrations with or without dexamethasone, As(2)O(3), thalidomide and zoledronic acid. Cell viability was assessed by trypan blue assay, plasma cell labeling index (PCLI) was detected by BrdU assay, terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay were used to determine apoptosis cells in situ. Synergistic effects of 2ME2 in combination with other drugs were judged by King's formula. The results showed that after treatment with 1, 4, 8, 12, 16 micromol/L 2ME2 at 12, 24, 36 and 48 hours respectively, 2ME2 caused a dose- and time-dependent inhibition of the cell viability. The concentration of 50% growth inhibition (IC(50)) was between (20.8 +/- 0.27) and (34.1 +/- 0.57) micromol/L. After treatment with 12 micromol/L 2ME2 within 24 hours, 2ME2 led to a progressive decline in the fraction of S-phase cells by BrdU assay, plasma cell labeling index (PCLI) declined from (30.14 +/- 4.28)% to (14.71 +/- 6.27)% (P < 0.05). After treatment with 1, 4, 8, 12, 16 micromol/L 2ME2 at 12, 24, 36 and 48 hours respectively, 2ME2 can induce a dose- and time-dependent apoptosis of myeloma cell lines. The percentage of apoptosis was between 9% - 33% (P < 0.05). Q value of synergistic effects was between 1.13 to 1.43. It is concluded that 2ME2 can inhibit proliferation and induce apoptosis of myeloma cell lines and has synergistic effects with dexamethasone, As(2)O(3), thalidomide and zoledronic acid.
Insights
2-methoxyestradiol (2ME2) inhibits myeloma cell growth and induces apoptosis in vitro. This estrogen derivative also shows synergistic effects when combined with dexamethasone, As(2)O(3), thalidomide, and zoledronic acid.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Multiple myeloma is a hematological malignancy characterized by uncontrolled proliferation of plasma cells.
- Current treatments for multiple myeloma have limitations, necessitating the exploration of novel therapeutic agents.
- 2-methoxyestradiol (2ME2), an endogenous estrogen metabolite, has demonstrated anti-cancer properties in various studies.
Purpose of the Study:
- To investigate the in vitro efficacy of 2-methoxyestradiol (2ME2) in inhibiting the growth of multiple myeloma cell lines.
- To determine the apoptosis-inducing potential of 2ME2 in myeloma cells.
- To evaluate the synergistic effects of 2ME2 in combination with established myeloma drugs.
Main Methods:
- Seven human myeloma cell lines were cultured and treated with varying concentrations of 2ME2.
- Cell viability was assessed using the trypan blue exclusion assay.
- Apoptosis induction was measured by BrdU and TUNEL assays, and synergistic effects were quantified using King's formula.
Main Results:
- 2ME2 demonstrated dose- and time-dependent inhibition of myeloma cell viability, with IC(50) values ranging from 20.8 to 34.1 µmol/L.
- Treatment with 2ME2 significantly reduced the plasma cell labeling index (PCLI) and induced apoptosis in a dose- and time-dependent manner (9%–33%).
- 2ME2 exhibited synergistic effects when combined with dexamethasone, As(2)O(3), thalidomide, and zoledronic acid, with Q values between 1.13 and 1.43.
Conclusions:
- 2-methoxyestradiol (2ME2) effectively inhibits proliferation and induces apoptosis in multiple myeloma cell lines in vitro.
- 2ME2 possesses synergistic activity when used in combination with dexamethasone, As(2)O(3), thalidomide, and zoledronic acid.
- These findings suggest that 2ME2 is a promising agent for further investigation in multiple myeloma therapy.
