Curcumin exerts antitumor effects in retinoblastoma cells by regulating the JNK and p38 MAPK pathways

Abstract

Curcumin, a naturally occurring polyphenolic compound present in turmeric (Curcuma longa), exerts antitumor effects in various types of malignancy. However, the precise mechanisms responsible for the effects of curcumin on retinoblastoma (RB) cells have not been fully explored. In the present study, the molecular mechanisms by which curcumin exerts its anticancer effects in RB Y79 cells were investigated. The results showed that curcumin reduced cell viability in Y79 cells. Curcumin induced G1 phase arrest through downregulating the expression of cyclin D3 and cyclin-dependent kinase (CDK)2/6 and upregulating the expression of CDK inhibitor proteins p21 and p27. Curcumin-induced apoptosis of Y79 cells occurred through the activation of caspases-9/-3. Moreover, flow cytometric analysis showed that curcumin induced mitochondrial membrane potential (∆Ψm) collapse in Y79 cells. We also found that curcumin induced the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). JNK and p38 MAPK inhibitors significantly suppressed curcumin‑induced activation of caspases-9/-3 and inhibited the apoptosis of Y79 cells. Taken together, our results suggest that curcumin induced the apoptosis of Y79 cells through the activation of JNK and p38 MAPK pathways. These findings provide a novel treatment strategy for human RB.

RETRACTED ARTICLE: Curcumin inhibits proliferation, migration, invasion and promotes apoptosis of retinoblastoma cell lines through modulation of miR-99a and JAK/STAT pathway

“…Besides, based on the data in the current study we inferred that curcumin-suppressed Rb cells proliferation might be via modulation of cell cycle, as CyclinD1 was down-regulated and p21 was up-regulated by addition of curcumin. Similar finding was reported by Yu et al [ 31 ] that curcumin induced G1 phase arrest via down-regulations of Cyclin D3, CDK2/6, and up-regulations of p21 and p27. CyclinD1 and p21 are two key molecules in cell-cycle progression.…”

“…Sreenivasan and his colleagues have reported that curcumin suppressed the expression of multidrug resistance associated protein 1 (MDR1) [ 29 ], thereby rendering Rb cells more sensitive to chemotherapy [ 30 ]. Another investigation demonstrated that curcumin induced the apoptosis of Y79 cells possibly through activating JNK and p38 MAPK pathways [ 31 ]. Although these authors have identified some anti-tumor activities of curcumin on Rb, additional studies are required to cross-check the anti-tumor properties of curcumin on other Rb cell types, and to decode the underlying mechanisms.…”

Pharmacogenomic Characterization and Isobologram Analysis of the Combination of Ascorbic Acid and Curcumin—Two Main Metabolites of Curcuma longa—in Cancer Cells

“…If applied alone, curcumin and AA were cytotoxic toward cell lines of different tumor types with curcumin exhibiting stronger cytotoxicity than AA. Our results are in line with other reports on the inhibitory activity of curcumin (Bimonte et al, 2016 ; Guzzarlamudi et al, 2016 ; Kasi et al, 2016 ; Ye et al, 2016 ; Yu et al, 2016 ; Zeng et al, 2016 ) and AA (Chen et al, 2015 ; Fukui et al, 2015 ; Jacobs et al, 2015 ; Sunil Kumar et al, 2015 ; Venturelli et al, 2015 ). The anticancer effects of curcumin in vitro and in vivo are primarily due to the activation of apoptotic pathways in cancer cells as well as the inhibition of mechanisms related to the tumor microenvironments such as inflammation, angiogenesis, invasion, and metastasis.…”

Curcumin as a Therapeutic Option in Retinal Diseases

“…Yu et al found than the activation of c-Jun N-terminal kinase (JNK) and p38 MAPK on the retinoblastoma Y79 cell line was induced by curcumin. This finding was corroborated by the use of SP600125 and SB203580, specific inhibitors of JNK and p38 MAPK respectively, which inhibited the apoptosis of the retinoblastoma cell line and suppressed the activation of caspase-9 and -3 [34]. Li et al studied the effect of curcumin on SO-Rb50 and Y79 cells, retinoblastoma cell lines, and found out that curcumin inhibited cell proliferation, induced apoptosis and inhibited the migratory and invasive capacities of the retinoblastoma cell lines.…”