Delphinidin, an anthocyanidin in pigmented fruits and vegetables, induces apoptosis and cell cycle arrest in human colon cancer HCT116 cells

Abstract

Because of unsatisfactory treatment options for colon cancer, there is a need to develop novel preventive approaches for this malignancy. One such strategy is through chemoprevention by the use of non-toxic dietary substances and botanical products. Delphinidin, an anthocyanidin in pigmented fruits and vegetables, possesses strong antioxidant and anti-inflammatory properties. In the present study, we investigated the antiproliferative and proapoptotic properties of delphinidin in human colon cancer HCT116 cells. We found that treatment of cells with delphinidin (30-240 μM; 48 h) resulted in (i) decrease in cell viability (ii) induction of apoptosis, (iii) cleavage of PARP, (iv) activation of caspases-3, -8, and -9, (v) increase in Bax with a concomitant decrease in Bcl-2 protein, and (vi) G2/M phase cell cycle arrest. NF-κB provides a mechanistic link between inflammation and cancer, and is a major factor controlling the ability of both pre-neoplastic and malignant cells to resist apoptosis-based tumor surveillance mechanisms. We therefore, determined the effect of delphinidin on NF-κB signaling pathway. The immunoblot, ELISA and EMSA analysis demonstrated that the treatment of HCT116 cells with delphinidin resulted in the inhibition of (i) IKKα, (ii) phosphorylation and degradation of IκBα, (iii) phosphorylation of NF-κB/p65 at Ser 536 , (iv) nuclear translocation of NF-κB/p65, (v) NF-κB/p65 DNA binding activity, and (vi) transcriptional activation of NF-κB. Our results suggest that delphinidin treatment of HCT116 cells suppressed NF-κB pathway, resulting in G2/M phase arrest and apoptosis. We suggest that delphinidin could have potential in inhibiting colon cancer growth.

Anthocyanins are novel AMPKα1 stimulators that suppress tumor growth by inhibiting mTOR phosphorylation

“…AIMs are largely composed of aglycoside anthocyanins, such as delphinidin-3-glucoside, petunidin-3-glucoside, and malvidin-3-glucoside. There are claims that the potent anthocyanins responsible for anticancer activities include delphinidin, cyanidin and malvidin (34,35). Although the major anthocyanins exerting most of anti-cancer activities of AIMs could be delphinidin-3-glucoside, petunidin-3-glucoside, and malvidin-3-glucoside, the diverse and unique composition of AIMs may represent the overall anti-cancer activities observed in this study.…”

The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer

“…Certain phytochemicals are particularly eligible for the single compound type modality inasmuch as they are pleiotropic modulators of manifold signal transduction pathways and exhibit relatively low toxicity in non-cancerous cells (Khan et al, 2008;Lee et al, 2011b). Unfortunately, the currently Food and Drug Administration (FDA)-approved chemotherapeutic phytochemicals such as paclitaxel, docetaxel, vinblastine, and vincristine have only a singular molecular target (tubulin), whereas other phytochemical candidates such as (-)-epigallocatechin gallate and delphinidin have multiple molecular targets (Ermakova et al, 2006;Li et al, 2007;He et al, 2008;Kang et al, 2008;Shim et al, 2008Shim et al, , 2010Hwang et al, 2009;Ozbay and Nahta, 2011) and in vitro cytostatic/cytotoxic potency (Bin Hafeez et al, 2008;Hsieh and Wu, 2009;Philips et al, 2009;Qiao et al, 2009;Yun et al, 2009;Cvorovic et al, 2010;Das et al, 2010) but lack an advanced clinical development trajectory and regulatory approval status.…”

Mechanism of Action of Nigella sativa on Human Colon Cancer Cells: the Suppression of AP-1 and NF-κB Transcription Factors and the Induction of Cytoprotective Genes

“…Upon activation by molecular cues, NF-κB dimer migrates to the nucleus, where it binds to a common DNA sequence, the κB-site, within the enhancer elements of the NF-κB target genes and promotes transcription (Pereira and Oakley, 2008). Contrary to this scenario, NF-κB has been found to be constitutively activated in colon cancer and the sustained activation of NF-κB underlies resistance of CRC cells to the apoptosis induced by various chemotherapeutic agents (Yun et al, 2009). Thereby, agents that can suppress NF-κB activation have the ability to suppress carcinogenesis and thus, have therapeutic potential (Aggarwal and Shishodia, 2006).…”