<p>A novel curcumin derivative CL-6 exerts antitumor effect in human gastric cancer cells by inducing apoptosis through Hippo&ndash;YAP signaling pathway</p>

Abstract

Purpose Gastric carcinoma is the second most frequently diagnosed cancer and leading cause of cancer death in China. As a new generation of cancer therapeutic drug, CL-6, a curcumin derivative, shows better bioavailability than curcumin, which has shown anticancer effects in gastric cancer (GC). However, whether CL-6 shows similar activities in GC has not been examined. Materials and methods Cell proliferation assay, colony-forming assay, flow cytometric analysis, wound healing assay, and Transwell invasion assay were performed to examine the effects of CL-6 on proliferation, apoptosis, migration, and invasion on human AGS and MGC-803 cell lines. Western blot was used to evaluate protein levels of Bax, Bcl-2, YAP, p-YAP, and Lats, and gene expression was measured by real-time quantitative PCR (RT-qPCR). Results CL-6 dose dependently reduced proliferation, increased apoptosis, and inhibited the migration and invasion abilities of AGS and MGC-803 cells. CL-6 also increased levels of pro-apoptotic protein Bax, decreased levels of antiapoptotic protein Bcl-2, and increased the Bax/Bcl-2 ratio. CL-6 treatment also inhibited YAP and YAP protein and mRNA expression, while it induced the expression of Lats and p-YAP (Ser127). Conclusion CL-6 induces apoptosis of GC cells by activating the Hippo–YAP signaling pathway. These results indicate the therapeutic potential of the novel curcumin derivative CL-6 in GC.

Investigation of anti-cancer and migrastatic properties of novel curcumin derivatives on breast and ovarian cancer cell lines

“…Curcumin is one such example which exhibits anti-cancer activity against various cancer types [42–47]. Curcumin has been replaced by more potent and bioavailable derivatives, which have attracted attention for the development of novel drugs [48]. The novel curcumin derivatives developed in this study has exhibited remarkable cytotoxicity (~ 100X) better than parent compound at nanomolar concentrations on a wide range of cancer cell lines which includes both representative liquid and solid tumour cell lines.…”

Overcoming cancer therapeutic bottleneck by drug repurposing

“…258 Further studies have confirmed the effects of curcumin on the Wnt/β-catenin and Hippo/YAP signaling pathways, inhibiting stemness or proliferation in multiple cancers. [259][260][261][262][263][264][265] Although limited bioavailability and stability hamper the application of curcumin in clinical cancer therapy, [266][267][268] curcumin has been used for treating patients with pancreatic cancer in clinical trials due to its anticancer activity and safety profile. 269,270 Drug repurposing of curcumin could prove beneficial for clinical translation using highly bioavailable forms of curcumin (e.g., micro-and nano-formulations of curcumin with greatly enhanced absorption) to target telomerase.…”

Context-dependent roles of YAP/TAZ in stem cell fates and cancer

“…In gastric cancer, YAP reduces apoptosis by promoting mitophagy downstream of SIRT1 activity, MFN2 expression, and upregulation of growth factors, whereas the targeting of YAP increases apoptosis [143][144][145]. In clear cell renal cell carcinoma [146] and rhabdomyosarcoma [147], YAP is upregulated, and YAP depletion increases apoptosis and decreases proliferation, even in murine xenografts in vivo.…”