Cocoa seed extract induces antiproliferative and pro-apoptotic effects in HT-29 colorectal cancer cells

The beneficial therapeutic actions of cocoa (Theobroma cacao L.) in the treatment of cancer, attributed to antioxidant and anti-inflammatory properties, are well-established. The aim of this study was to investigate the anticarcinogenic effect of cocoa on colorectal cancer cells (HT-29) via modulation in cancer hallmarks and enabling characteristics. For this, HT-29 cells were exposed to different cocoa concentrations (100-2000 µg/ml) for 72 hr. Further, the effect of cocoa was examined in conjunction with the IC₅₀ of 5-fluorouracil (5-FU), a drug utilized in the treatment of colon cancer, for 72 h. After the incubation period, analyses to achieve some of the cancer biomarkers were conducted, including cell cycle, apoptosis, cell‑colony formation, gene and protein expression, genotoxicity, oxidative stress, and energy metabolism. Data demonstrated that cocoa did not interfere with the action of 5-FU. Although isolated cocoa exhibited cytotoxic action on HT-29 cells at concentrations ≥ 750 µg/ml, an increase in production of oxidative stress, inhibition of formation of colonies, activation of apoptosis and necrosis, by increase expression of the protein linked with apoptosis (AIF) and accompanied by a reduction in expression of poly (ADP-ribose) polymerase (PARP), upregulation caspase 1 and 8, cell‑cycle arrest, induction of genotoxicity and cell energy metabolism modulation. Taking this into account, the results indicate that cocoa may be considered as a potent anticarcinogenic adjuvant agent, with an effective profile to be used in new therapies for colorectal cancer (CRC).