Oleandrin Research Articles

Targeting stress induction of GRP78 by cardiac glycoside oleandrin dually suppresses cancer and COVID-19

BackgroundDespite recent therapeutic advances, combating cancer resistance remains a formidable challenge. The 78-kilodalton glucose-regulated protein (GRP78), a key stress-inducible endoplasmic reticulum (ER) chaperone, plays a crucial role in both cancer cell survival and stress adaptation. GRP78 is also upregulated during SARS-CoV-2 infection and acts as a critical host factor. Recently, we discovered cardiac glycosides (CGs) as novel suppressors of GRP78 stress induction through a high-throughput screen of clinically relevant compound libraries. This study aims to test the possibility that agents capable of blocking stress induction of GRP78 could dually suppress cancer and COVID-19.ResultsHere we report that oleandrin (OLN), is the most potent among the CGs in inhibiting acute stress induction of total GRP78, which also results in reduced cell surface and nuclear forms of GRP78 in stressed cells. The inhibition of stress induction of GRP78 is at the post-transcriptional level, independent of protein degradation and autophagy and may involve translational control as OLN blocks stress-induced loading of ribosomes onto GRP78 mRNAs. Moreover, the human Na+/K+-ATPase α3 isoform is critical for OLN suppression of GRP78 stress induction. OLN, in nanomolar range, enhances apoptosis, sensitizes colorectal cancer cells to chemotherapeutic agents, and reduces the viability of patient-derived colon cancer organoids. Likewise, OLN, suppresses GRP78 expression and impedes tumor growth in an orthotopic breast cancer xenograft model. Furthermore, OLN blocks infection by SARS-CoV-2 and its variants and enhances existing anti-viral therapies. Notably, GRP78 overexpression mitigates OLN-mediated cancer cell apoptotic onset and suppression of virus release.ConclusionOur findings validate GRP78 as a target of OLN anti-cancer and anti-viral activities. These proof-of-principle studies support further investigation of OLN as a readily accessible compound to dually combat cancer and COVID-19.

Structure identification of potential compound as selective renal anticancer isolated from Nerium indicum Mill. Leaves

Oleandrin is one of cardenolida compound isolated from an active fraction of Nerium indicum Mill leaves. (fam. Apocynaceae), which have cytotoxic effect on several human cancer cells, and also to normal cells in vitro. Another compound which was potential as renal anticancer has also been isolated from N. indicum. However, its chemical structure has not been discovered. The aim of this study was to identify the potential compound as selective to renal cancer present in the leaves of N. indicum. The potential compound was isolated from the active fraction using Preparative TLC and structure elucidation was done by using spectroscopic methods (UV, IR, MS and NMR). Base on this spectra and by comparison with oleandrin data, it was indicated that the potential compound as Renal anticancer was as 16,17-dehydrodeacetyl-5a-oleandrin. Key word: N.indicum, oleandrin, cytotoxic, renal anticancer, spectroscopic

Cytotoxicity of oleandrin isolated from the leaves of Nerium indicum Mill. on several human cancer cell lines

Finding anticancer drugs from natural resources still proceeds. Oleandrin isolated from Nerium indicum Mill. inhibited the growth of mieloma cell line in vitro better than that of vincristine sulphate. This study was aimed to determine the cytotoxic effect of oleandrin on various human cancer cell lines. Cytotoxic test of oleandrin on seven human cancer cell lines was done by SRB-method. The analysis was conducted by comparing the ID50 of oleandrin with that of doxorubicin and cisplatin as positive controls. This result indicated that oleandrin possessed the best cytotoxic effect on breast cancer (MCF7) with ID50 at 8.85 nM. Keywords : Oleandrin, cytotoxicity, human cancer cells, ID50