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[Proliferation inhibiting and apoptosis inducing effects of parthenolide on human multiple myeloma cells]
Zhi-chao Chen1, Qiu-bai Li, Jing Shao
1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Objective:
To investigate the effect of parthenolide (PTL) on human multiple myeloma (MM) cells in vitro and its mechanism.
Methods:
Human MM cells of the line PRMI8266 were cultured and treated with PTL of the concentrations of 1, 2.5, 5, 7.5, and 10 micromol/L for 24, 48, or 72 hours. MM cells treated with DMSO were used as control group. The optical density was measured so as to draw a growth curve. The cell viability was detected by MTT and trypan-blue exclusion. The apoptosis was detected by flow cytometry. AO/EB staining and Wright-Giemsa staining were used to observe the morphological changes of the cells by fluorescence microscope and light microscope respectively. The caspase-3 activity was evaluated by BD ApoAlert Caspase Colorimetric Assay Kit.
Results:
PTL significantly inhibited the proliferation and viability of the MM cells time and dose-dependently (all P < 0.01), and significantly induced the cell apoptosis after 48 h in a dose-dependent manner (P < 0.01). The early cell apoptosis rates for PTL of the concentrations of 2, 5 and 10 micromol/L were 17.1% +/- 2.6%, 33.6% +/- 3.8%, and 40.9% +/- 3.1% respectively, all significantly higher than that of the control group (5.6% +/- 1.2%, all P < 0.01). The MM cells treated with PTL of the concentration of 5 micromol/L for 48 h showed typical cell apoptotic features. The caspase-3 activity of the MM cells was enhanced significantly by PTL in a time and dose-dependent manner (all P < 0.01).
Conclusion:
This first report of anti-proliferation and apoptosis induction effects of PTL on MM cells shows that able to significantly inhibit the proliferation and induce the apoptosis of MM cells and enhance the caspase-3 activity, PTL may be a potentially useful drug for treatment of MM.
Insights
Parthenolide (PTL) effectively inhibits human multiple myeloma (MM) cell proliferation and viability. This study demonstrates PTL
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Context:
- Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells.
- Existing MM treatments face challenges with drug resistance and toxicity, necessitating novel therapeutic strategies.
- Parthenolide (PTL), a sesquiterpene lactone, has shown cytotoxic effects in various cancer cells.
Purpose:
- To investigate the in vitro anti-proliferative and apoptosis-inducing effects of PTL on human MM cells.
- To elucidate the underlying mechanism of PTL's action on MM cells, including caspase-3 activation.
Summary:
- Human MM cells (PRMI8266) were treated with varying concentrations of PTL (1-10 µmol/L) for 24-72 hours.
- PTL significantly inhibited MM cell proliferation and viability in a time- and dose-dependent manner (P < 0.01).
- PTL induced significant apoptosis in MM cells, evidenced by flow cytometry, morphological changes, and enhanced caspase-3 activity (P < 0.01).
Impact:
- This study provides the first report on the anti-proliferative and apoptosis-inducing effects of PTL in MM cells.
- PTL demonstrates potential as a therapeutic agent for multiple myeloma by inhibiting cell growth and inducing programmed cell death.
- The findings suggest PTL warrants further investigation as a novel drug candidate for MM treatment.
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