Anticancer activity in human multiple myeloma U266 cells: synergy between cryptotanshinone and arsenic trioxide

Abstract

Arsenic trioxide (As2O3) has been recently established as one of the most effective drugs for the treatment of patients with acute promyelocytic leukemia. However, it has exhibited to be less efficient for the non-promyelocytic leukaemia or other types of malignant tumors. The purpose of the present study was to explore new therapeutic strategies based on As2O3 for human multiple myeloma. Here, we first report cryptotanshinone (CPT) and As2O3 synergy for enhanced cytotoxicity in human multiple myeloma U266 cells. In particular, the apoptosis related proteins (e.g., cleaved poly (ADP-ribose) polymerase (PARP), caspase-3 and -9) were significantly increased by the combination treatment (iAs(III) + CPT), whereas, the expression of survival proteins such as Bcl-2 and survivin was suppressed, suggesting that the induction of apoptosis through mitochondrial-mediated apoptotic pathway. In addition, there were no appreciable effects observed in cells after exposure to either As2O3 or CPT alone. In order to better understand the molecular mechanism, we further determined the phosphorylation of STAT3, JNK, ERK and p38. Interestingly, phosphorylation of JNK and p38 were remarkably induced by combination treatment, and no significant inhibition of STAT3 or ERK was observed. In addition, induction of apoptosis in human multiple myeloma cells was partially abrogated only by pretreatment with JNK inhibitor and not by p38 inhibitor, suggesting that JNK pathway may play an important role in induction of apoptosis by the combination of iAs(III) and CPT. Further studies are needed to evaluate this synergistic anticancer effect in vivo. In the near future, this new approach might be used clinically for multiple myeloma (MM) treatment.

Cryptotanshinone potentiates the antitumor effects of doxorubicin on gastric cancer cells via inhibition of STAT3 activity

“…Western blot analysis was performed as previously described. 34 Briefly, gastric cancer cells were washed in phosphate-buffered saline, lysed for 30 min using RAPI extraction buffer (Beyotime Institute of Biotechnology, Jiangsu, China) containing freshly prepared protease inhibitors (Merck, Germany) and then centrifuged for 5 min at 14,000 rpm at 4℃. The protein concentration of the supernatant was determined using the BCA protein assay (Pierce, Rockford, IL, USA).…”

2‐(Pro‐1‐ynyl)‐5‐(5,6‐dihydroxypenta‐1,3‐diynyl) Thiophene Induces Apoptosis Through Reactive Oxygen Species‐Mediated JNK Activation in Human Colon Cancer SW620 Cells

“…Mitochondria from cultured cells were isolated as described previously (Liu et al, ). In brief, 2 × 10 7 cells were frozen and thawn to weaken the cell membrane, and then suspended in ice‐cold homogenization buffer A [230 mM Mannitol, 70 mM sucrose, 10 mM Tris‐HCl, is‐HCl 0% of homo sub‐1 mM EDTA·2Na and 0.5% bovine serum albumin (BSA), pH 7.4] and incubated for 10 min on ice.…”

Arsenic-Based Anticancer-Combined Therapy: Novel Mechanism Inducing Apoptosis of Cancer Cells

“…Jian et al showed that ATO upregulates cereblon, the antimyeloma target of LEN, thus potentiating the sensitivity of MM cells [98]. The anti-myeloma activity of ATO was also enhanced by the combination strategies with a vitamin E analog Trolox [99], a specific MEK inhibitor PD325901 [100], a natural quinoid diterpene cryptotanshinone (also known as STAT3 inhibitor) [101,102], and a phytochemical sulforaphane [103].…”