Invitro Evaluation of Torin2 and 2, 6-Dihydroxyacetophenone in Colorectal Cancer Therapy

Abstract

Colorectal cancer (CRC) is one of the most prevalent cancers diagnosed worldwide. Despite recent advances, resistance to cytotoxic and targeted therapy remains one of the greatest challenges in long-term management of colorectal cancer therapy. Recently established role of mTOR signaling in proliferation of CRC has incited for evaluation of mTOR kinase specific inhibitors in CRC therapy. Second generation mTOR kinase inhibitors including Torin2 has demonstrated efficient anticancer properties against variety of cancers and are in various stages of drug development. The time and financial constraints concomitant from discovery to development of efficient chemical inhibitors has redirected attention towards investigation of wide spread naturally occurring largely inexpensive compounds for their therapeutic potential. One such naturally occurring compound acetophenone derivative polyphenolic compound 2, 6-Dihydroxyacetophenone (DHAP) inhibits cell growth in different conditions. We investigated anticancer properties of both Torin2 and DHAP against colorectal cancer in HCT8 cell lines. Both Torin2 and DHAP inhibited growth of CRC cells at different concentrations by restricting multiple cellular functions e.g., cell cycle progression, cell migration and induced apoptosis. Treatment of HCT8 cells with natural compound DHAP resulted in reduced expression of mTOR pathway specific genes p70S6K1 and AKT1. In silico docking studies showed affinity of DHAP to mTOR kinase like Torin2. Taken together, our result vouches for role of Torin2 in CRC therapy and recommends DHAP an mTOR inhibitor, as a potential lead in the development of new therapeutic regimes against colorectal cancer.

Anti-Arthritic and Anti-Cancer Activities of Polyphenols: A Review of the Most Recent In Vitro Assays

“…Chang et al have also conducted cell proliferation assays with human synovial cell lines [ 62 ]. The fluorescent microscopic technique has been used to detect morphological changes upon treatment with various polyphenols in various cancer and RA cell lines [ 63 , 64 ]. It has become an excellent technique for cell and tissue imaging and to observe biological processes.…”

Natural and Synthetic Anticancer Epidrugs Targeting the Epigenetic Integrator UHRF1

“…Another possibility is that Torin-2 suppresses UHRF1 expression independently of mTORC1 [ 118 ]. Torin-2 treatment led to growth inhibition and the induction of apoptosis in colorectal [ 121 ], small-cell lung cancer, and non-small-cell lung cancer [ 122 ], highlighting the potential of Torin-2 as an anti-cancer agent. Moreover, a recent study reported that UHRF1 silencing could increase the radiosensitivity of ESCC (esophageal squamous cell carcinoma) through the inhibition of the PI3K/Akt/mTOR signaling pathway [ 123 ].…”

Widely targeted metabolomics reveals stamen petaloid tissue of Paeonia lactiflora Pall. being a potential pharmacological resource

“…Besides, both arbutin [62] and its derivatives 6'-p-coumarylarbutin [63] have strong inhibitory effect on human tyrosinase activity and arbutin is commonly used as a powerful skin whitening agent in cosmeceuticals [64]. Also, 2',6'-dihydroxyacetophenone [65] is a bioactive phenolic acid with anticancer properties. In addition, camelliaside A can relieve burns via inhibiting inflammation and enhancing collagen synthesis [66], and shows obvious neuroprotective activity [67].…”