Anticancer effect of celastrol on human triple negative breast cancer: Possible involvement of oxidative stress, mitochondrial dysfunction, apoptosis and PI3K/Akt pathways

Celastrol inhibits growth and metastasis of human gastric cancer cell MKN45 by down‐regulating microRNA‐21

“…In addition, previous studies demonstrated that celastrol inhibited the PI3K/AKT and NF-κB survival pathway in human breast cancer (Shrivastava, Jeengar, Reddy, Reddy, & Naidu, 2015). Moreover, miR-21 can affect cancer cell growth via regulating the PTEN/AKT and NF-κB pathways (He et al, 2015;Ni et al, 2018;S.…”

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

“…In addition to autophagy, celastrol is able to eliminate cancer cells by different apoptotic pathways, including (1) upregulation of death receptors in breast and colon cancer, enhancing TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis (90, 91); (2) activation of Fas/Fas ligand pathway in non-small-cell lung cancer (92); (3) inhibition of mitochondrial respiratory chain (MRC) complex I, and consequently ROS accumulation inside cancer cells, in non-small-cell lung carcinoma, liver cancer (93), osteosarcoma (94) and hepatocellular carcinoma (95) cell lines; (4) mitochondrial dysfunction and PI3K/Akt/mTOR pathway inhibition in triple negative breast cancer (96), melanoma cells (97) and several other types of cancer (98); (5) reduction in phosphorylated Akt, mTOR, and S6K and increase in AMP-activated protein kinase (AMPK) phosphorylation in gastric cancer cell lines and xenografts (79); (6) AMPK-induced PLK-2 pathway in breast cancer cell line (99); (7) destabilization of the ErbB2 and estrogen receptors in breast cancer cells (100, 101); (8) activation of caspase-dependent and independent pathways in breast cancer cells (102); (9) inhibition of topoisomerase II in HL-60 leukemia cells (103); (10) mitochondrial instability, activation of caspases and downregulation AML1-ETO/C-KIT oncoprotein, thus inhibiting the Akt, STAT3 and Erk1/2 downstream pathways in acute myeloid leukemia (AML) t(8:21) translocation cell line (104); (11) inhibition of STAT3/Janus kinase 2 (JAK2) in hepatocellular carcinoma (105); (12) inhibition of Myb in AML cells, while not affecting normal hematopoietic progenitor cells (106); (13) induction of the unfolded protein response-dependent cell death, endoplasmic reticulum (ER) stress, and PERK-eukaryotic initiation factor 2 (eIF2)–activating transcription factor (ATF4)-C/EBP homology protein (CHOP) signaling in oral squamous cell carcinoma cell lines (107); (14) reduction of GSK3β levels in HeLa cells (108); (15) target proteostasis in human glioblastoma cells, potentiating the proteotoxic stress response of HSP inhibitors (109); (16) targeting AR, ERG, and NF-kB signaling pathways in prostate cancer (110, 111); (17) upregulation of miR-146a expression, suppressing the NF-kB activity in gastric cancer (112); (18) inhibition of NF-kB in multiple myeloma (113–115), prostate cancer (116, 117) and leukemia cells (118); and (19) downregulation of IL-6 gene expression via NF-kB inhibition in prostate carcinoma cells (119). …”

Novel therapeutic strategies for patients with triple-negative breast cancer

“…While MES tumors tend to frequently activate KRAS, BRAF, and RAS pathways, some may activate JAK-2/STAT3 97. The current study has demonstrated that celastrol-induced apoptosis in TNBC cells might be mediated through mitochondrial dysfunction and PI3K/Akt axis, while PI3K/Akt/mTOR inhibitor PF-04691502 and mTOR inhibitor, rapamycin, enhanced the effect of celastrol-induced apoptosis in TNBC cells 98. However, focusing on therapeutic targets geared toward the most commonly known activated pathways such as P53, MAPK, PI3K/AKT, Jak-2, KRAS, BRAF, and RAS and incorporating gene expression in advanced TNBC treatment.…”