The cancer has an increasing trend around the world. Physicians and researchers have been trying to improve the general condition of cancer patients using different methods of chemotherapy, radiation therapy and surgery [1–3]. However, despite the development of therapeutic interventions, development of novel chemotherapeutics, the mortality rate of patients with CRC is still high . Therefore, the application of novel alternative compounds in various extracts will be promising for inducing cell death (apoptosis) in cancer cells. It has been shown that hydroalcoholic extract of some algal species had significantly higher anticancer effects than other extracts against cancer cells [19–21]. In another study, alcoholic and chloroform extracts of Polysiphonia lanosa were significantly more effective against DLD-1 and HTC-116 CRC cell lines . Moreover, Gracilaria edulis methanolic extract had significantly higher effect against HT-29 CRC cells .
In this study, the effect of hydroalcoholic extract of S. oligocystom was evaluated against several CRC cell lines. The 50% cell cytotoxicity (LD50) of S. oligocystom against SW742, HT-29, WiDr and CT-26 cell lines after 24h included 0.5, 1, 1 and 0.5mg/mL, respectively (Fig. 1). After 48h, the LD50 of this algae included 0.2, 0.5, 0.5 and 0.2 mg/mL, respectively. Moreover, LD90 of this algae was > 2mg/mL after 24h and > 1mg/mL after 48h for all cell lines. The results exhibited that concentration of ≥ 0.5mg/mL of S. oligocystom can be considered for anticancer therapies. It has been verified that Sargassum spp have antioxidant and anticancer effects against some cancer cell lines such as HepG2, Hela, MDA-MB-231, MCF-7, HT-29 and LNCap in vitro. We also did not assess the in vivo results. In previous studies, Sargassum spp has conferred anticancer effects at higher concentrations [21–26].
In the trypan blue test, in the concentration of 4mg/mL of S. oligocystom, a mean of 96% of cells were killed, and at concentrations 2, 1, 0.5, 0.2 and 0.1 mg/mL, 91%, 81%, 56%, 31 and 11% of them were killed, respectively. There was no significant difference among various cell lines, but a significant viability decrease was observed at concentrations ≥ 1mg/mL. It is crucial to determine a special dose for anticancer treatment using more exact verification of anticancer effects of S. oligocystom because of potential effects in this study.
We also observed that S. oligocystom can increased the expression of APC gene, a regulatory gene necessary for the control of cell division. One of the most common mutations in the CRC development includes the inactivation of the APC gene which results in uncontrolled cells proliferation and polyp development. However, patients with APC mutations have the risk of developing CRC approximately at the age of 40 . The APC protein from mutation is truncated, abnormal, and dysfunctional. This short protein cannot prevent cell overgrowth, thus leading to the formation of polyps that can become cancerous. APC is also involved in the demonstration of microtubules by binding to the PD2 domain. APC inactivation can be initiated after specific chain reactions in the cytoplasm . Mutations in the APC gene mostly occur early in cancers, such as CRC. Human develop the CRC due to mutations in the APC gene.
In addition, P53 acts as a guardian of the genome to maintain genome stability by preventing incidence of mutations. This suggests that the TP53 gene plays an important role in preventing cancer formation, with proteins encoded by TP53 binding to DNA and regulating gene expression to prevent genome mutation (in normal cells P53 binds to its negative regulator, MDM2 complex). Following DNA damage or other stresses, different pathways lead to the dissociation of P53 and the MDM2 complex. P53 activation causes the cell cycle arrest and allows cell repair or apoptosis [29, 30].