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Updated: Sep 11, 2026

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics
Published on: January 11, 2019
2',2'-Difluorodeoxycytidine (gemcitabine) induces apoptosis in myeloma cell lines resistant to steroids and
Abstract:
The paucity of effective cytotoxic agents for the treatment of steroid resistant multiple myeloma explains the ongoing search for alternative substances for chemotherapy of this disease. In the present study, the purine antagonist 2-chlorodeoxyadenosine (2-CdA, cladribine) and the pyrimidine antagonist 2',2'-difluorodeoxycytidine (gemcitabine) were tested on four myeloma cell lines (i.e., U 266, OPM 2, RPMI 8226, IM 9), one plasma cell leukemia cell line (HS Sultan) and a myeloid control cell line (HL 60), all of which are resistant to 10-6 M dexamethasone. Gemcitabine has been found to be promising in the chemotherapy of other tumors with low proliferative activity, but its effectiveness against myeloma cells has not been analyzed so far. In our tests, gemcitabine induced a significant degree of apoptosis in all cell lines investigated. After incubation for 48 h with 10 microM gemcitabine, the median numbers of apoptotic cells were in the range of 45% in the OPM 2 and 79% in the U 266 cell line. All of the investigated cell lines were responsive to concentrations of 10 microM gemcitabine even after an exposure of only 30 min, three of them (U 266, HS Sultan, IM 9) also responded to a concentration of 10 nM. Higher concentrations and longer exposure times were necessary to suppress the growth of normal hematopoietic bone marrow progenitor cells. In contrast to gemcitabine, standard concentrations of 2-CdA (i.e., 30 and 300 nM) failed to induce a significant degree of apoptosis in the cell lines investigated but inhibited the growth of myeloid progenitor cells. The results suggest that gemcitabine induces apoptosis in myeloma and plasma cell leukemia lines resistant to steroids and 2-CdA. The fact that tumor cell apoptosis was achieved at concentrations clinically achievable and tolerable, which at the same time do not inhibit the growth of normal CFU-GM progenitor cells, favors the initiation of phase I trials with this drug for the treatment of multiple myeloma.
Insights
Gemcitabine effectively induces apoptosis in steroid-resistant multiple myeloma and plasma cell leukemia cell lines. This pyrimidine antagonist shows promise for treating these resistant cancers, unlike 2-chlorodeoxyadenosine.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Steroid-resistant multiple myeloma necessitates novel chemotherapeutic agents.
- Existing treatments for multiple myeloma have limitations, driving research into alternative therapies.
Purpose of the Study:
- To evaluate the efficacy of gemcitabine and 2-chlorodeoxyadenosine (2-CdA) against steroid-resistant multiple myeloma and plasma cell leukemia cell lines.
- To compare the apoptotic effects of gemcitabine and 2-CdA on cancer cells versus normal bone marrow progenitor cells.
Main Methods:
- In vitro testing of gemcitabine and 2-CdA on multiple myeloma, plasma cell leukemia, and myeloid cell lines resistant to dexamethasone.
- Assessment of apoptosis induction and cell growth inhibition at various drug concentrations and exposure times.
Main Results:
- Gemcitabine significantly induced apoptosis in all tested myeloma and plasma cell leukemia lines, even at low concentrations and short exposure times.
- 2-CdA failed to induce significant apoptosis in these cell lines but inhibited normal myeloid progenitor cells.
- Gemcitabine demonstrated efficacy at clinically achievable concentrations without harming normal bone marrow progenitor cells.
Conclusions:
- Gemcitabine is a potent inducer of apoptosis in gemcitabine- and steroid-resistant multiple myeloma and plasma cell leukemia.
- Gemcitabine's selective toxicity profile supports its potential as a therapeutic agent for multiple myeloma.
- Further clinical investigation, including Phase I trials, is warranted for gemcitabine in treating multiple myeloma.
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