SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

Abstract

Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in particular drug-resistant cancer, is of great importance. The aim of the present study was to explore the potential of a next-generation taxoid, SB-T-121205, in modulating the proliferation, migration and invasion of paclitaxel-resistant human breast cancer cells (MCF-7/PTX) and further evaluate the underlying molecular mechanisms. The results of MTT assay showed that SB-T-121205 has much higher potency to human breast cancer cells (MCF-7/S, MCF-7/PTX and MDA-MB-453 cells) than paclitaxel, while that the non-tumorigenic human bronchial epithelial cells (BEAS-2B) were slightly less sensitive to SB-T-121205 than paclitaxel. Flow cytometry and western blot methods revealed that SB-T-121205 induced cell cycle arrest at the G2/M phase and apoptosis in MCF-7/PTX cells through accelerating mitochondrial apoptotic pathway, resulting in reduction of Bcl-2/Bax ratio, as well as elevation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) levels. Moreover, SB-T-121205 changed epithelial-mesenchymal transition (EMT) property, and suppressed migration and invasion abilities of MCF-7/PTX cells. Additionally, SB-T-121205 exerted antitumor activity by inhibiting the transgelin 2 and PI3K/Akt pathway. These findings indicate that SB-T-121205 is a potent antitumor agent that promotes apoptosis and also recedes migration/invasion abilities of MCF-7/PTX cells by restraining the activity of transgelin 2 and PI3K/Akt, as well as mitochondrial apoptotic pathway. Such results suggest a potential clinical value of SB-T-121205 in breast cancer treatment.

Transgelin-2 is a novel target of KRAS-ERK signaling involved in the development of pancreatic cancer

“…It is well-known that the homologue of transgelin-2, transgelin (SM22), plays an important role in migration and differentiation [ 48 ]. Several drugs including statins, Salvianolic acid A, Paeonol and SB-T-121205 regulate cancer cell metastasis and are associated with transgelin-2 expression [ 49 – 52 ]. Transgelin-2 is also involved in endothelial cell motility and tube formation, which involves the phosphorylation of myosin light chain followed by actin-myosin interaction [ 49 ].…”

Hydrous icaritin nanorods with excellent stability improves the in vitro and in vivo activity against breast cancer

“…Antitumor treatment was performed on MCF-7 tumor-bearing nude mice model using PTX injection as a positive control (Fujioka et al, 2017;Zheng et al, 2017). As seen in Figure 5(A, B), daily oral administration of free HICT (35 mg/ kg) showed no antitumor effect with a similar tumor growth profile to that of normal saline group, probably due to its poor solubility and oral bioavailability of HICT suspensions even in the presence of TPGS and SO.…”

Curcumin and paclitaxel induce cell death in breast cancer cell lines

“…Paclitaxel is a first-line therapeutic clinical agent used to treat breast cancer, which exerts its antitumor activity by promoting the polymerization of tubulin and stabilizing the resulting microtubules, causing cell cycle arrest that leads to apoptosis of cancer cells (7). However, paclitaxel resistance often occurs after a short period of treatment, causing a serious problem in chemotherapy that eventually results in the patient succumbing to the disease due to tumor metastasis (7,8).…”