Steviol, a natural product inhibits proliferation of the gastrointestinal cancer cells intensively

Abstract

New anticancer agents with lower toxicity have been always urged because of drug resistance associated with overused chemotherapy agents. In this study, steviol, a colonic metabolite of natural sweetener and also a component in leaves of stevia rebaudiana bertoni, was found to possess intensive anticancer activity on the human gastrointestinal cancer cells. Steviol inhibited six human gastrointestinal cancer cells intensively as 5-fluorouracil did at 100 μg/mL. The inhibition mechanism follows mitochondrial apoptotic pathway that was evidenced by increase of Bax/Bcl-2 ratio, activation of p21 and p53; and caspase 3-independent mechanism was also involved. These results are consistent with the miRNA expression analysis. The most regulated miRNAs in the steviol treated gastrointestinal cancer cells were miR-203a-3p (log2 =1.32) and miR-6088 (log2 =-2.54) in HCT-116, miR-1268b (log2 =19.85) and miR-23c (log2 =-2.05) in MKN-45. In view of the metabolic characteristics of steviol and its cytotoxicity on the cancer cells, steviol could be a chemotherapy agent potentially for cancer treatment.

Neuroendocrine and Metabolic Effects of Low-Calorie and Non-Calorie Sweeteners

“…Intriguingly, pre-clinical evidence suggests that steviol glycoside derivatives can exert antiproliferative properties in several cancer cell lines, including pancreatic ( 100 ), breast ( 101 ), and gastric cancer ( 102 ) cell lines.…”

‘Sweeter’ than its name: anti-inflammatory activities of Stevia rebaudiana

“…metastasis) (Germano et al 2008;Grivennikov et al 2010;Hanahan and Weinberg 2011;Arvelo et al 2016). The anti-cancer and antioxidant potential of stevia and its chemical constituents have been suggested by researchers for more than 10 years (Konoshima and Takasaki 2002;Yasukawa et al 2002;Mizushina et al 2005;Masuda et al 2006;Bhattacharyya et al 2009;Chen et al 2018). As a high intake of antioxidants can prevent the accumulation of free radicals or oxidative stress generated by injury or even infections, they can essentially decrease cancer risk.…”

A Computational Study of Steviol and Its Suggested Anticancer Activity. A DFT and Docking Study

“…Cancer has become one of the leading causes of death worldwide 1,2 . Some studies indicate that obesity and high caloric intake may be associated with different types of cancer including, breast, and hormone related ones 2,3 .…”

“…The main drawback of actual oncology medication includes severe side effects, and nonspecificity on cancer cells. Therefore, the development of new therapies is needed 1,3 . Literature shows that around 75% of new anticancer drugs are extracted or made from natural products 3 .…”

“…Many other benefits of Steviol that have been reported include immunomodulatory, antiinflammatory, diuretic, anti-hypertensive, anti-hyperglycemic, antioxidant and anti-tumor activity [3][4][5] . Moreover, it has been reported that Steviol is active against gastrointestinal cancer in 6 cell types and against breast cancer in MCF-7 cells 1,3 . Steviol significantly inhibits gastrointestinal cancer cell proliferation by inducing G1 cell cycle arrest and mitochondrial apoptosis, as evidenced by the increased Bax/Bcl-2 ratio 1 .…”