Curcumin Induces Pancreatic Adenocarcinoma Cell Death Via Reduction of the Inhibitors of Apoptosis

Abstract

Objectives The inhibitor of apoptosis (IAP) proteins are critical modulators of chemotherapeutic resistance in various cancers. To address the alarming emergence of chemotherapeutic resistance in pancreatic cancer, we investigated the efficacy of the turmeric derivative curcumin in reducing IAP protein and mRNA expression resulting in pancreatic cancer cell death. Methods The pancreatic adenocarcinoma cell line PANC-1 was used to assess curcumin’s effects in pancreatic cancer. Curcumin uptake was measured by spectral analysis and fluorescence microscopy. AlamarBlue and Trypan blue exclusion assays were used to determine PANC-1 cell viability following curcumin treatment. Visualization of PANC-1 cell death was performed using Hoffman Modulation Contrast microscopy. Western blot and PCR analyses were used to evaluate curcumin’s effects on IAP protein and mRNA expression. Results Curcumin enters PANC-1 cells and is ubiquitously present within the cell following treatment. Furthermore, curcumin reduces cell viability and induces morphological changes characteristic of cell death. Additionally, curcumin decreases IAP protein and mRNA expression in PANC-1 cells. Conclusions These data demonstrate that PANC-1 cells are sensitive to curcumin treatment. Furthermore, curcumin as a potential therapeutic tool for overcoming chemotherapeutic resistance mediated by IAPs, supports a role for curcumin as part of the therapeutic approach for pancreatic cancer.

Cytotoxicity of Standardized Curcuminoids Mixture against Epithelial Ovarian Cancer Cell Line SKOV-3

“…Besides reflecting the growth and fission of cells, these biological characteristics of cell morphology reflect the apoptotic phenotype. The main morphological hallmarks of apoptotic cells are membrane blebs and cell shrinkage [27]. Therefore, cellular morphological changes can be investigated to evaluate cell apoptosis qualitatively.…”

“…While curcuminoids are composed of three main members-curcumin, DMC, and BDMC-all have shown efficient anticancer effects against various malignancies and induce apoptosis, but with different potencies. Although many studies present curcumin as the active ingredient in turmeric, with a strong ability to kill different cancer cells such as hepatic [37], lung [28], breast [38], pancreas [27], bladder [30], and ovarian [39] cancer cells, DMC, which is more stable than curcumin, was reported by Simon et al [40] to exhibit the strongest antitumor activity among the three curcuminoids against breast cancer cells. DMC has also shown ability to inhibit the growth of prostate cancer cells [32].…”

Yin Yang 1 (YY1): Regulation of Survivin and Its Role In Invasion and Metastasis

“…Interestingly, curcumin is also showing promise as a sensitizing agent to ionizing radiation in Burkitt’s type lymphoma and non-Hodgkin lymphoma 64,65 and alone in its ability to reduce expression of multiple IAPs critical to chemoresistance in pancreatic cancer cell lines. 66 The natural agents resveratrol and quercetin in combination (RQ) have also shown a similar downregulation of Sp proteins and their targets, including surviving. 67 Interestingly, the investigators cite RQ’s antioxidant capabilities (as opposed to curcumin’s generation of reactive oxygen species) as the potential reason for this observed repression of Sp proteins and their transcriptional targets such as survivin.…”

Curcumin – A review on multipotential phytocompound

“…Evidence has been provided for the treatment of many human cancers, including pancreatic cancer, by its derivative named polyphenol [17,18].…”