Curcumin Nanoparticle Enhances the Anticancer Effect of Cisplatin by Inhibiting PI3K/AKT and JAK/STAT3 Pathway in Rat Ovarian Carcinoma Induced by DMBA

Abstract

Cisplatin has been used for decades for the treatment of ovarian cancer. However, despite its potent anticancer effect, cisplatin’s efficacy as a single agent was inadequate in patients with advanced stage. Curcumin has been shown to sensitize cisplatin activity in several cancer models. However, the low bioavailability of curcumin has limited its anticancer potential. Hence, nano-formulation of curcumin was developed to increase its therapeutic efficacy in ovarian cancer. The objective of this study was to investigate the mechanism of curcumin nanoparticles given in combination with cisplatin in rat ovarian carcinoma induced by dimethylbenz(a)anthracene (DMBA). The administration of cisplatin and nanocurcumin resulted in a significant reduction in ovarian tumor volume and weight. Furthermore, there were reduction in expressions of Ki67, TGF-β, PI3K, and Akt phosphorylation. Co-treatment of cisplatin and nanocurcumin also reduced JAK expression, STAT3 phosphorylation, and reduced IL-6 concentrations. Altogether, nanocurcumin, given as a co-treatment with cisplatin has therapeutic potential in ovarian cancer models by inhibiting proliferation through downregulation of PI3K/Akt and JAK/STAT3 signaling pathways.

Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells

“…Cur can increase the generation of ROS, which leads to many dysfunctions in cells, including DNA damage, cell apoptosis, and cell cycle arrest in CRC [ 15 , 16 , 17 ]. Cur also exhibits an antitumor effect as an inhibitor of the transcription factor signal transducer and activator of transcription 3 (STAT3) in various tumors [ 18 , 19 , 20 , 21 ], and STAT3 is reported to upregulate the expression of NNMT in CRC [ 22 ]. In addition, it has been reported that Cur potentiates the effect of many chemotherapy drugs, including 5-FU [ 18 , 23 , 24 ].…”

“…Cur also exhibits an antitumor effect as an inhibitor of the transcription factor signal transducer and activator of transcription 3 (STAT3) in various tumors [ 18 , 19 , 20 , 21 ], and STAT3 is reported to upregulate the expression of NNMT in CRC [ 22 ]. In addition, it has been reported that Cur potentiates the effect of many chemotherapy drugs, including 5-FU [ 18 , 23 , 24 ]. It has been observed that, regardless of the drug that it is combined with, Cur always results in an enhanced effect with reduced dose and side effects [ 23 ].…”

Interaction between Curcumin and β-Casein: Multi-Spectroscopic and Molecular Dynamics Simulation Methods

“…Curcumin is a natural polyphenol compound derived from turmeric, and commonly used as a natural colorant [ 1 ]. Compared with artificial synthetic food additives, curcumin is nontoxic [ 2 ] and has anti-inflammatory [ 3 ], antibacterial [ 4 ], anti-cancer [ 5 ], and antioxidant [ 6 ] effects. However, curcumin has poor water solubility, low bioavailability and tends to degrade at neutral and basic conditions, limiting its use in functional foods.…”

Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

“…Combination treatment of curcumin and cisplatin managed to inhibit phosphorylation of JAK and STAT3 in ovarian and papillary thyroid cancer cells leading to enhanced proliferation and reduced stemness of potential cancer stem cells ( Khan AQ. et al, 2020 ; Sandhiutami et al, 2021 ). In osteosarcoma cells, curcumin inhibited the p -JAK2/p-STAT3 pathway which was involved in lung metastasis whereas in lung cancer, curcumin suppressed activation of p-STAT3 both in vitro and in vivo ( Alexandrow et al, 2012 ; Sun et al, 2019 ).…”