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Cancer Stem Cells as a Prognostic Biomarker and Therapeutic Target Using Curcumin/ Piperine Extract for Multiple
Sara A Mekkawy1, Mohga S Abdalla2, Mohamed M Omran2
1Molecular Biotechnology program, Faculty of Science, Helwan University, Cairo, Egypt.
Background:
Multiple myeloma (MM) is a hematological bone marrow malignancy that can be treated but is usually fatal. Medication resistance is the major cause of relapses due to cancer stem cells (CSCs). As a result, this study aimed to identify multiple myeloma cancer stem cells (MMCSCs) in the bone marrow of twelve MM patients with pathological complete response (pCR) after chemotherapy and to investigate the potential effect of Curcumin/Piperine (C/P) extract as an anti-MMCSCs treatment in twenty newly diagnosed patients.
Methods:
This study included twenty bone marrow (BM) samples from newly diagnosed MM patients and twelve BM samples from pCR patients after a year of treatment. The MTT test was performed to assess the treatment's effective dosage. A flow cytometer was used to identify MMCSCs, cell cycle profile, extract's apoptotic activity, and proliferation marker in the selected samples. Also, a colony formation test and stemness protein were investigated.
Results:
In newly diagnosed MM patients, the C/P extract suppressed MMCSCs by 64.71% for CD138-/CD19- and 38.31% for CD38++. In MM patients' samples obtained after one year of treatment, the MMCSCs inhibition percentage reached 44.71% (P < 0.008) for CD138-/CD19- and 36.94% (P < 0.221) for CD38++. According to cell cycle analyses, the number of cells treated with C/P extract was significantly reduced in the S and G0/G1 phases (87.38%: 35.15%, and 4.83%: 2.17% respectively), with a rapid increase in the G2/M phases (1.1%: 2.2%.). MMCSCs apoptosis was identified using a flow cytometer and Annexin-V. Multiple myeloma stem cell (MMCSC) proliferation was inhibited. Clonogenicity was suppressed by 60%, and stemness protein expression was reduced by 70%.
Conclusion:
MMCSCs in the bone marrow of MM-pCR patients can be utilized as a prognostic tool to predict recurrent multiple myeloma incidence. Also, the therapeutic potential of C/P extract as a prospective anti-MM drug targeting MMCSCs.
Insights
Curcumin/Piperine extract effectively targets multiple myeloma cancer stem cells (MMCSCs), reducing their numbers and inhibiting proliferation. This natural compound shows promise as a novel therapeutic agent for multiple myeloma treatment.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Multiple myeloma (MM) is a fatal bone marrow cancer where drug resistance, driven by cancer stem cells (CSCs), causes relapse.
- Identifying multiple myeloma cancer stem cells (MMCSCs) is crucial for understanding and overcoming treatment resistance.
Purpose of the Study:
- To identify MMCSCs in bone marrow of MM patients achieving pathological complete response (pCR) post-chemotherapy.
- To investigate the anti-MMCSC effects of Curcumin/Piperine (C/P) extract in newly diagnosed MM patients.
Main Methods:
- Utilized flow cytometry to identify MMCSCs, analyze cell cycle, apoptosis, and proliferation markers.
- Conducted MTT assays for dosage determination, colony formation tests, and stemness protein analysis.
- Included bone marrow samples from newly diagnosed MM patients and those in pCR after treatment.
Main Results:
- C/P extract suppressed MMCSCs by up to 64.71% in newly diagnosed patients and 44.71% in pCR patients.
- The extract significantly reduced cells in S and G0/G1 phases, increasing G2/M phase, indicating cell cycle arrest.
- Demonstrated inhibition of MMCSC proliferation, clonogenicity (60% suppression), and stemness protein expression (70% reduction).
Conclusions:
- MMCSCs in pCR patients can serve as a prognostic marker for predicting MM recurrence.
- Curcumin/Piperine extract exhibits therapeutic potential as an anti-MM drug targeting MMCSCs.
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