Ficus dubia Latex Extract Induces Cell Cycle Arrest and Apoptosis by Regulating the NF-κB Pathway in Inflammatory Human Colorectal Cancer Cell Lines

Abstract

Colorectal cancer is one of the most diagnosed cancers that is associated with inflammation. Ficus dubia latex is recognized as a remedy with various therapeutic effects in traditional medicine, including anti-inflammatory and antioxidant activity. The present study aims to compare the anti-tumor activity of Ficus dubia latex extract (FDLE) against HCT-116 and HT-29 human colorectal cancer cell lines in normal and inflammatory condition and explore its mechanism of action. FDLE exhibited remarkable antiproliferative activity against HCT-116 and HT-29 colorectal cancer cell lines in both conditions using MTT and colony formation assays and more effective anti-proliferation was observed in inflammatory condition. Mechanistically, FDLE induced cell cycle arrest at G0/G1 phase by down-regulating NF-κB, cyclin D1, CDK4 and up-regulatingp21 in both cell in normal condition. In inflammatory condition, FDLE not only exhibited stronger induction of cell cycle arrest in both cells by down-regulating NF-κB, cyclin D1, CDK4 and down-regulating p21, but also selectively induced apoptosis in HCT-116 cells by down-regulating NF-κB and Bcl-xl and up-regulating Bid, Bak, cleaved caspase-7 and caspase-3 through stronger ability to regulate these proteins. Our results demonstrated that the phytochemical agent in the latex of Ficus dubia could potential be used for treatment and prevention of human colorectal cancer, especially in inflammation-induced hyperproliferation progression.

Study on the effect and mechanism of Lacticaseibacillus rhamnosus AFY06 on inflammation-associated colorectal cancer induced by AOM/DSS in mice

“…NF-κB is a major link between inflammation and cancer; thus, it plays a crucial role in colorectal cancer occurrence and development through its mediated transcription. NF-κB signaling activation promotes the establishment of a pro-inflammatory tumor microenvironment in colorectal cancer cells and regulates cell proliferation, apoptosis, metastasis, angiogenesis, drug resistance, and inflammation-related target gene expression ( Hu et al, 2022 ). Simultaneously, NF-κB is a major anti-apoptotic factor.…”

Anti-Inflammatory and Anti-Adipocyte Dysfunction Effects of Ficus lindsayana Latex and Root Extracts

“…In addition, the root ethanolic extract displays potent antidiabetic effects through the inhibition of α-glucosidase, one of the drug targets for diabetes, and anticancer activity against lung- and ovarian-cancer cell lines with genome-safe [ 31 ]. Moreover, it was found that the latex extract has the potential for the prevention and treatment of human colorectal cancer through the regulation of the inflammatory pathway [ 33 , 34 ]. Although FL has been reported to have the potential against inflammation and diabetes, there is no scientific information of its bioactive compounds and biological activity on inflammation-associated adipocyte dysfunction, which is a major cause of insulin resistance and diabetes (T2DM).…”