Introduction: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a
member of the Tumor Necrosis Factor (TNF) superfamily, which stimulates apoptosis in a wide range of cancer
cells through binding to Death Receptors 4 and 5 (DR4/5). Nevertheless, TRAIL has noticeable anti-cancer
abilities; some cancer cells acquire resistance to TRAIL, and consequently, its potential for inducing apoptosis
in target cells is strongly diminished. Acute lymphoblastic leukemia MOLT-4 cell line is one of the most resistant
cells to TRAIL that developed resistance to TRAIL through different pathways. TRAIL plus kaempferol
was used to eliminate the resistance of the MOLT-4 cells to TRAIL.
Materials and Methods: Firstly, IC50 for kaempferol (95μM) was determined by using the MTT assay. Secondly,
the viability of the MOLT-4 cells was assayed by FACS after Annexin V/PI staining, following treatment
with TRAIL (50 and 100nM) and kaempferol (95μM) alone and in combination. Finally, the expression levels
of the candidate genes involved in resistance to TRAIL were assayed by real-time PCR technique.
Results: Kaempferol plus TRAIL induced apoptosis robustly in MOLT-4 cells at 12, 24 and 48 hours after
treatment. Additionally, it was found that kaempferol could inhibit the expression of c-FLIP, X-IAP, cIAP1/2,
FGF-8 and VEGF-beta, and conversely augment the expression of DR4/5 in MOLT-4 cells.
Conclusion: It is suggested that co-treatment of MOLT-4 cells with TRAIL plus kaempferol is a practical and
attractive approach to eliminate cancers’ resistance to TRAIL by inhibition of the intracellular anti-apoptotic
proteins, upregulation of DR4/5 and also by suppression of the VEGF-beta (VEGFB) and FGF-8 expressions.