β-Cryptoxanthin Synergistically Enhances the Antitumoral Activity of Oxaliplatin through ΔNP73 Negative Regulation in Colon Cancer

Abstract

Background: The acquired resistance to chemotherapy represents the major limitation in the treatment of cancer. New strategies to solve this failure and improve patients' outcomes are necessary. The cancer preventive effect of b-cryptoxanthin has been widely described in population studies. Few reports support its putative use as an antitumoral compound. Here we focus on the therapeutic potential of b-cryptoxanthin individually or in combination with oxaliplatin in colon cancer and try to decipher the molecular basis underlying its effect.Methods: Apoptosis, viability and proliferation assays, mouse models, and an intervention study in 20 healthy subjects were performed. A PCR array was carried out to unravel the molecular putative basis of the b-cryptoxanthin effect, and further signaling experiments were conducted. Comet Assay was completed to evaluate the genotoxicity of the treatments.

Marine Carotenoids against Oxidative Stress: Effects on Human Health

“…A very recent human intervention study [ 62 ] focused on the therapeutic potential of β-cryptoxanthin individually and in combination with oxaliplatin in colon cancer: β-cryptoxanthin decreased the proliferation of cancer cells and cooperated with oxaliplatin to induce apoptosis through the negative regulation of NH 2 -terminally truncated p73 (ΔNP73). The administration of anti-tumoral drugs such as oxaliplatin can decrease in the presence of β-cryptoxanthin to achieve same percentage of growth inhibition.…”

“…The combined regimen produced greater benefits than either individual modality, without increasing side effects. Additionally, the concentration-limiting toxicity of oxaliplatin is reduced in presence of this antioxidant carotenoid [ 62 ].…”

The Biochemistry and Antioxidant Properties of Carotenoids

“…β-Cryptoxanthin has been reported to decrease lung cancer through downregulating neuronal nicotinic acetylcholine receptor α7/PI3K signaling pathway [75]. In addition to lung cancer, β-cryptoxanthin enhances the action of a chemotherapeutic agent, oxaliplatin, to treat colon cancer [76]. Moreover, high lycopene and β-cryptoxanthin including diet might protect against aggressive prostate cancer [77].…”

A Review of the Biological Activities of Microalgal Carotenoids and Their Potential Use in Healthcare and Cosmetic Industries

“…However, recent in vitro, in vivo, and human-intervention studies report that β-cryptoxanthin can differentially regulate the expression of P73 variants. In addition, these studies have found that this carotenoid has the ability to inhibit the proliferation of colon cancer cells and in conjunction with oxaliplatin, can induce apoptosis in cancer cells by negatively regulating ΔNP73 [ 111 ].…”