Curcumin is an APE1 redox inhibitor and exhibits an antiviral activity against KSHV replication and pathogenesis

Abstract

Curcumin, a polyphenol, is the main bioactive compound in dietary spice turmeric curcuma longa.It possesses anti-inflammatory, anti-oxidant and anti-neoplastic properties and shows potentials in treating or preventing particular diseases such as oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, hyperlipidemia and cancers. The diverse range and potential health beneficial effects has generated enthusiasm leading to intensive investigation into the phytochemical. However, a concern has been also raised if curcumin has a promiscuous bioassay profile and is a Pan-Assay INterference compound (PAINS). Here we present evidence indicating that curcumin is not a PAINS, but an inhibitor to APE1 redox function that affects many genes and pathways. This discovery explains the wide range of effects of curcumin on diverse human diseases and predicts a potential application in treatment of viral infection and virus-associated cancer. As a proof-of-concept, we demonstrated that curcumin is able to efficiently block Kaposi's sarcoma-associated herpesvirus replication and inhibit the pathogenic processes of angiogenesis and cell invasion.

Curcumin exerts protective effects against hypoxia‑reoxygenation injury via the enhancement of apurinic/apyrimidinic endonuclease�1 in SH‑SY5Y cells: Involvement of the PI3K/AKT pathway

“…However, these effects were all blocked by curcumin, and the results indicated that curcumin increased APE1 expression and activity in cerebral I/R injury. However, an earlier study revealed that curcumin is an inhibitor of the APE1 redox function that affects numerous genes and pathways, which is contrary to the results of the current study (42). These differences may be a result of the different research systems used: The previous study examined a virus system, while the present study investigated SH-SY5Y cells.…”

Curcumin as an Antiviral Agent

“…Replication Human immunodeficiency virus [11] APE1 redox reactions Replication Kaposi's sarcoma-associated herpesvirus [12] Cell lipogenesis Replication Dengue virus [8]…”

“…Li et al [12] noted while reviewing the genes and pathways impacted by curcumin that there was overlap with pathways controlling the redox reaction of apurinic/apyrimidinic endonuclease 1 (APE1), suggesting curcumin could inhibit APE1 redox reactions. Since Kaposi's sarcoma-associated herpesvirus (KSHV) replication requires the redox function of APE1 [76], the authors investigated whether curcumin could inhibit KSHV replication.…”

“…Primary effusive lymphoma (PEL) BCBL-1 cells that were latently infected with KSHV were treated with TPA to induce activation of KSHV and subsequently treated with curcumin. Treatment with 30 µM of curcumin effectively blocked reactivation of KSHV by lowering expression of the switch gene replication and transcription activator (RTA), and the delayed-early gene K8 [12]. Curcumin treatment reduced both the intra-and extracellular KSHV genomic DNA levels (IC50 of 8.76 µM and EC50 of 6.68 µM, respectively) [12], indicating that curcumin is an effective treatment for KSHV infection.…”

Potential therapeutic effect of turmeric contents against SARS-CoV-2 compared with experimental COVID-19 therapies: in silico study

“…Y. Chen et al, 2013;C¸ıkrıkc¸I et al, 2008;Dhillon et al, 2008;S. C. Gupta et al, 2013;H. Li et al, 2019;Mathew & Hsu, 2018;Narayanan et al, 2012;Prasad & Tyagi, 2015;Si et al, 2007).…”