Synergistic Effect of Garcinol and Curcumin on Antiproliferative and Apoptotic Activity in Pancreatic Cancer Cells

Abstract

Pancreatic cancer (PaCa) is a major health concern due to its aggressiveness and early metastasis. Current treatments for PaCa are limited by development of resistance against therapy. As an alternative strategy, we assessed the combinatorial effect of dietary compounds, garcinol and curcumin, on human PaCa cells (BxPC-3 and Panc-1). A significant (P < 0.05) dose-dependent reduction in cell viability and increase in apoptosis were observed in both cell lines as compared to untreated controls. A combination index (CI) value < 1, for a two-way comparison of curcumin and garcinol, suggests synergism. The potency (Dm) of the combination of garcinol and curcumin was 2 to 10 fold that of the individual agents. This indicates that curcumin and garcinol in combination exhibit a high level of synergism, with enhanced bioactivity, thereby reducing the required effective dose required for each individually. This combinatorial strategy may hold promise in future development of therapies against PaCa.

Garcinol: Current status of its anti-oxidative, anti-inflammatory and anti-cancer effects

“…Moreover, elevated oncogenic miRNA-21 levels are observed in breast, colon and pancreatic cancers [61][62][63]. Garcinol also downregulated the expression level of miRNA-21 in the human pancreatic cancer cell lines BxPC-3 and Panc-1 [42]. Taken together, these novel discoveries of garcinol's ability to inhibit p300/PCAF and downregulate oncogenic miRNA make it an attractive agent to modulate gene expression and affect downstream PD events in various cancer types.…”

Apoptosis and Autophagy Induction As Mechanism of Cancer Prevention by Naturally Occurring Dietary Agents

“…Curcumin and a dietary compound, garcinol resulted in a synergistic effect against pancreatic cancer. The combination of garcinol and curcumin significantly inhibited cell viability and caused induction of apoptosis via upregulation of caspase-3 and -9 activity in BxPC-3 and Panc-1 cell lines [88]. A BRCA-mutated ovarian cancer cell treated with STAT3 inhibitor HO-3867, a novel curcumin analog, exhibited a significant degree of apoptosis with increased levels of cleaved caspase-3, caspase-7 and PARP, and induced ROS.…”

Curcumin increases efficiency of γ-irradiation in gliomas by inhibiting Hedgehog signaling pathway

“…39 There are also numbers of research revealed that Curcumin has specific regulation to Hedgehog signaling pathway and EMT process 7,40,41 in several cancer cells including pancreas, colon, leukemia, prostate carcinoma and glioblastomas. 8,[42][43][44] Islam SS et al and Xu X et al 9,10 point out that the Hedgehog signaling pathway activates EMT process to promote tumorigenicity and stemness. It is potent that Tsai, C. L.…”