Reyhaneh Moradi-Marjaneh, Seyed Mahdi Hassanian, Farzad Rahmani, Seyed Hamid Aghaee‐Bakhtiari, Amir Avan and Majid Khazaei*
Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin as well as the underlying molecular mechanism in CRC, has not been explored yet.
Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry respectively. Phytosomal curcumin was also tested for its in vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxide-dismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue.
Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect.
Conclusions: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.
Colorectal cancer, Phytosomal curcumin, angiogenesis, oxidative stress, xenograft
Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad