Time - and Concentration - Dependent Effects of Resveratrol on miR 15a and miR16-1 Expression and Apoptosis in the CCRF-CEM Acute Lymphoblastic Leukemia Cell Line

Abstract

Background: Chemotherapy is one of the common approaches in treatment of cancers, especially leukemia. However, drug resistance phenomena reduce the likelihood of treatment success. Resveratrol is a herbal compound which through complicated processes makes some selected cells sensitive to treatment and induction of apoptosis. In the present study, the effects of resveratrol on the expression of miR 15a and miR16-1 and apoptosis in the CCRF-CEM cell line were investigated. Materials and Methods: The CCRF-CEM cell line was cultured under standard conditions and changes in miR 15a and miR 16-1 expression were analyzed by real time-PCR technique, with attention to reveratrol dose and time dependence. Also, apoptosis is evaluated by flow cytometry using annexin V and PI. Results: CCRF-CEM cells underwent dose-dependent apoptotic cell death in response to resveratrol. MiR 15a and miR 16-1 expression was up-regulated after 24 and 48 hours resveratrol treatment (p<0.05). Conclusions: The results of our study indicate that resveratrol induces apoptosis in a time and dosedependent manner in CCRF-CEM cells. Also, increased expression level of miR 16-1 and miR 15a by means of resveratrol in CCRF-CEM cells might have a role in apoptosis induction and predisposition. According to our results resveratrol can be regarded as a dietary supplement to improve efficacy of anti-leukemia therapies.

Apoptotic effect of resveratrol on human T‐ALL cell line CCRF‐CEM is unlikely exerted through alteration of BAX and BCL2 promoter methylation

“…[1][2][3][4] trans-3,5,4ʹ-Trihydroxystilbene (resveratrol) is an antioxidant component of red wine which exists in approximately 70 plant species including peanut, pines, mulberry, and grape. Despite the availability of huge number of chemotherapeutic drugs, detrimental side effects and high risk of relapse following remission remained as the major challenges as for the use of these conventional modalities.…”

Biological Activities of Resveratrol against Cancer

“…Wu discovered that treatment with RSV (20-100 µM) induced apoptosis and phosphorylation of histone H2AX in CML K562 cells through regulation of P38 and JNK, which are associated with the MAPK pathway [236]. When acute lymphoblastic leukemia (ALL) CCRF-CEM cells were treated with RSV, there was dose-dependent cell death along with upregulation of miR16-1 and miR15a expressions, as analyzed by real-time polymerase chain reaction [237]. A study concluded that RSV inhibited proliferation of T-cell ALL cells by inducing cell cycle arrest, apoptosis, and autophagy through suppression of the Akt/mTOR/p70s6k/4E-BP1 pathway and activation of the P38-MAPK signaling pathway [238].…”

Chemoprevention by resveratrol and pterostilbene: Targeting on epigenetic regulation

“…In addition, increased expression level of miR 16‐1 and miR 15a by means of resveratrol in CCRF‐CEM cells might have a role in apoptosis induction and predisposition. According to the results, resveratrol can be regarded as a dietary supplement to improve the efficacy of antileukemia therapies . Fan et al investigated the molecular effects of miR‐155 on cardiac hypertrophy, focusing on the role of breast cancer type 1 susceptibility protein (BRCA1).…”