Abstract
Background: Acute lymphoblastic leukemia (ALL) is an aggressive malignancy defined by accumulation of lymphoblasts in the bone marrow. Leukemic stem cells (LSCs) are the major cause of the recurrence and metastasis of ALL. This study aimed to develop an effective anti-cancer agent targeting these LSCs. Luffa Cylindrica (L.C.) leaves extract was selected to evaluate its effect on ALL via eradicating the LSCs as it contains many active anti-cancer flavonoids. Methods:Thirty-two bone marrow samples of ALL patients were used in this study. LSCs population was identified in the selected samples. Cell viability was measured by MTT assay and flow cytometry. Cell cycle, apoptosis, proliferation marker; ki-67 and colony forming assay were further analyzed. Results:This study revealed the expression of CD34+/CD38+ cells in addition to CD34+/CD38- population and the extract was effective against the two LSCs populations. MTT assay showed that treated leukemic cells exhibited significant reduction in the viable cells in a dose dependent manner with IC50 of 3 µg/µl which was then confirmed by flow cytometry. Cell cycle analysis results showed significant reduction in the percentage of cells treated with L.C. extract in both the S and G0/G1 phases, with concomitant increase in the G2/M phase. Also, L.C. extract could effectively induce apoptosis, inhibit proliferation and suppress colonogenecity of leukemic cells. Conclusion:This study validated the medicinal potential of L.C. leaves extract as a promising anti-leukemic agent targeting both LSCs and blasts in ALL patients, which may be explained by the synergy found between its potent flavonoids especially apigenin, luteolin and kaempferol.
Highlights
Leukemia, the blood or bone marrow cancer was resulted from the overproduction of numerous numbers of abnormal white blood cells
This study validated the medicinal potential of L.C. leaves extract as a promising anti-leukemic agent targeting both Leukemic stem cells (LSCs) and blasts in Acute lymphoblastic leukemia (ALL) patients, which may be explained by the synergy found between its potent flavonoids especially apigenin, luteolin and kaempferol
The present results showed that the 100% cell proliferation of the leukemic cells was significantly reduced in a dose-dependent manner to 88.27%, 80.79%, 65.53% and 50% upon treatment with 0.5, 1, 2 and 3 μg/ μl of L.C. leaves extract respectively
Summary
The blood or bone marrow cancer was resulted from the overproduction of numerous numbers of abnormal white blood cells (namely called blasts). LSCs are regulated by critical surface antigens like CD34 and CD38 proteins These proteins are expressed in most cases of leukemia, and are used as specific cell markers in both diagnosis and prognosis of the disease (Jiang et al, 2016). Targeting these cells will provoke a great revolution in the cancer therapy. Conclusion: This study validated the medicinal potential of L.C. leaves extract as a promising anti-leukemic agent targeting both LSCs and blasts in ALL patients, which may be explained by the synergy found between its potent flavonoids especially apigenin, luteolin and kaempferol
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