Anti-lung cancer mechanisms of diterpenoid tanshinone via endoplasmic reticulum stress-mediated apoptosis signal pathway / 中国中药杂志

At present, lung cancer ranks second and first respectively in the incidence and the mortality among malignant tumors. It is urgent to find new effective anti-lung cancer drugs with less side effects and relatively defined mechanisms. Endoplasmic reticulum stress (ERS)-mediated apoptosis pathway is an effective way to promote tumor cell apoptosis; diterpenoid tanshinone (DT), an effective part separated from Salviae Miltiorrhizae Radix et Rhizoma, was found to have an anti-lung cancer effect in previous studies via ERS-induced PERK-EIF2α pathway. In this paper, human lung adenocarcinoma PC9 cell line and nude mouse transplantation tumor model were applied to verify the anti-lung cancer effect of DT in vivo and in vitro, and illuminate the potential mechanism via ERS induced IRE1α/caspase 12 apoptosis pathway. The results showed that in vivo, DT could promote PC9 cell apoptosis in a concentration-dependent manner, up-regulate Bip, IRE1 and TRAF2 protein expressions in tumor tissue, reduce tumor weight and alleviate bodyweight loss. In vitro, DT inhibited the proliferation of PC9 cell line in a concentration-dependent manner, and destroyed the structure of mitochondria in PC9 cell, promoted Bax, IRE1α, Bip, TRAF2 and caspase 12 protein expressions, lower Bcl-2 protein expression in a time-dependent manner. DT shows a good effect on anti-lung cancer both in vivo and in vitro. The mechanism is related to the activation of ERS-induced IRE1α/caspase 12 apoptosis pathway and the promotion of cell apoptosis. ERS-mediated apoptosis pathway may be an important target of DT on anti-lung cancer.

Inhibition of diterpenoid tanshinones from Salvia miltiorrhiza Bge.on xanthine oxidase activity / 中国药理学与毒理学杂志

AIM Inhibitors of xanthine oxidase (XOD) may be potentially useful for the treatment of gout or other XOD inducing diseases, so the inhibition on XOD activity of diterpenoid tanshinones such as cyptotanshinone (CT) and methylenetanshinone (MT) from Tanshen (Salvia miltiorrhiza Bge.) was studied. METHODS The formation rate of uric acid from xanthine was determined by measuring the absorbance increment at 290 nm (ΔA290 nm) in the reactive medium of xanthine/XOD when CT or MT was added. RESULTS It was found that CT and MT inhibited XOD activity. Dixon plots showed that the inhibition mode was competitive type. The Ki values of CT and MT were 17.8 μmol·L-1 and 25.9 μmol·L-1, respectively. Their inhibitory potencies positively correlated with their concentrations and the IC50 values of CT and MT were 70 and 67 μmol·L-1, respectively. The IC50 value of allopurinol, the positive control, was 60 μmol·L-1. CONCLUSION CT and MT have inhibitory effects on XOD activity and may be potentially useful for the treatment of gout or other XOD inducing diseases.