Norcantharidin combined with paclitaxel induces endoplasmic reticulum stress mediated apoptotic effect in prostate cancer cells by targeting SIRT7 expression

Abstract

Prostate cancer (PCa), an extremely common malignancy in males, is the most prevalent disease in several countries. Norcantharidin (NCTD) has antiproliferation, antimetastasis, apoptosis, and autophagy effects in various tumor cells. Nevertheless, the antitumor effect of NCTD combined with paclitaxel (PTX), a chemotherapeutic drug, in PCa remains unknown. The cell growth, proliferative rate, cell cycle distribution, and cell death were determined by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyltetrazolium bromide, colony formation assay, PI staining, and Annexin V/PI staining by flow cytomertry, whereas the mitochondrial membrane potential (MMP) and endoplasmic reticulum (ER) stress was evaluated using the MitoPotential assay and ER‐ID red assay. We also evaluated the protein and mRNA expression of SIRTs by Western blotting and qRTPCR assay. Overexpression effectivity was measured by DNA transfection assay. Our study showed that cell viability and proliferative PC3 and DU145 rates were effectively inhibited after NCTD‐PTX combination. We also found that NCTD‐PTX combination treatment significantly enhance G2/M phase arrest, induction of cell death and ER stress, loss of MMP, and ER‐ or apoptotic‐related protein expression. Furthermore, NCTD‐PTX combination treatment was significantly decreasing the protein and mRNA expression of SIRT7 in PCa cells. Combination therapy effectively reduced cell viability, ER stress‐mediated apoptosis and p‐eIF2α/ATF4/CHOP/cleaved‐PARP expression inhibition in SIRT7 overexpression of PCa cells. These results indicate that NCTD combined with PTX induces ER stress‐mediated apoptosis of PCa cells by regulating the SIRT7 expression axis. Moreover, combination therapy may become a potential therapeutic strategy against human PCa.

RBM15 m6A modification‐mediated OTUB2 upregulation promotes cervical cancer progression via the AKT/mTOR signaling

“…CC is a malignant gynecological cancer with high morbidity and mortality globally 39–41 . Despite great advancement in the therapeutic approaches for CC in recent years, the median survival period of CC patients at advanced stages remains only 16.8 months 42,43 .…”

LncRNA RHPN1‐AS1 inhibition induces autophagy and apoptosis in prostate cancer cells via the miR‐7‐5p/EGFR/PI3K/AKT/mTOR signaling pathway

“…In some cellular contexts, autophagy acts as a cell survival pathway that prevents tumor cells from inducing apoptosis in response to cancer therapy, whereas in other settings, prolonged stress and progressive autophagy may ultimately lead to cell death, either in concert with apoptosis, or as a backup mechanism 20,21,32,33 . TEM revealed that the accumulation of AO puncta, the formation of autophagosomes, and the increased LC3‐I/LC3‐II conversion all induced autophagy 34 .…”

Norcantharidin induces ferroptosis via the suppression of NRF2/HO‑1 signaling in ovarian cancer cells

“…In non-small cell lung cancer, NCTC has been demonstrated to trigger apoptotic cell death, by activating mitophagy-mediated autophagy signaling ( 39 ). In prostate cancer cells, NCTD has been revealed to induce endoplasmic reticulum stress-mediated apoptosis via suppressing SIRT1 ( 40 ). However, NCTD has not been previously reported to induce ferroptosis in other cell types.…”