Antiproliferative activity and apoptosis induction by trijuganone C isolated from the root of Salvia miltiorrhiza Bunge (Danshen)

Abstract

In this study, we found that the hexane fraction of Danshen, the dried root of Salvia miltiorrhiza (Lamiaceae), exerted antiproliferative effects on human leukemia cells. Phytochemical investigation of the hexane fraction achieved the isolation of the tanshinone diterpenes: dihydrotanshinone I (1), trijuganone C (2), trijuganone B (3), cryptotanshinone (4), tanshinone IIA (5), and tanshinone I (6). Compound 2 showed significant antiproliferative activities against human leukemia cells HL-60, Jurkat, and U937. The antiproliferative activities of 2 against human cancer and normal cells indicated that 2 exhibited potent antiproliferative activities with IC values less than 10 μM against HL-60 and Jurkat cells as well as on the colon cancer cells DLD-1, COLO 205, and Caco-2. Compound 2 induced chromatin condensation, DNA fragmentation, activation of caspase-3, -8, and -9, and the cleavage of poly (ADP-ribose) polymerase (PARP) in HL-60 cells. Moreover, 2 activated Bid and Bax, leading to the loss of mitochondrial membrane potential, and 2 induced the cytochrome c release from mitochondria into cytosol. In contrast, Bcl-2 and Bcl-xL were unaffected by 2. These results suggest that 2 exerts antiproliferative effects via apoptosis induction mediated by mitochondrial dysfunction and caspase activation. Compound 2 may serve as a candidate of potential chemotherapeutic agent for human leukemia.

<p>Pharmacological Activity and Mechanism of Tanshinone IIA in Related Diseases</p>

“…It has the effects of relieving pain, promoting blood circulation, and removing blood stasis. 2 Modern pharmacological research has found that Salvia miltiorrhiza has dilated coronary artery, 3 prevents myocardial ischemia, 4 myocardial infarction 5 improves microcirculation, 6 and reducing myocardial oxygen consumption. 7 In Asian countries, for hundreds of years, Salvia miltiorrhiza is widely used against various heart complications.…”

Liquiritin and Liquiritigenin Induce Melanogenesis via Enhancement of p38 and PKA Signaling Pathways

“…Cell viability was determined by the MTT assay as described previously [42,43,44]. In brief, B16-F1 cells were seeded in 96-well plates at a density of 0.3 × 10 4 cells/well.…”

An In Vitro Evaluation of the Molecular Mechanisms of Action of Medical Plants from the Lamiaceae Family as Effective Sources of Active Compounds against Human Cancer Cell Lines

“…An important subgroup of terpenoid compounds is tanshinone diterpenoids, which are produced by Salvia miltiorrhiza roots; these are also connected with the induction of apoptosis in cancer cells. Increases in apoptosis were observed in colon cancer cells (human colorectal cancer DLD-1, human colon carcinoma COLO 205, and human colorectal adenocarcinoma Caco-2) exposed to trijuganone C [ 271 ], prostate cancer cells (PC3 and LNCaP) treated with tanshinone analog 2-(Glycine [methyl ester]methyl)-naphtho [ 272 ], and lung (human non-small cell lung cancer PC9 and A549) and breast cancer (MCF-7) cells administered by tanshinone [ 273 ]; these changes were attributed to the upregulation of numerous apoptotic factors including cytochrome c, pro- and antiapoptotic proteins ratio, caspases, PARP, p53, and p38. In addition, MCF-7 cells treated with three tanshinones isolated from the roots of Perovskia abrotanoides (cryptotanshinone, tanshinone 2A, and hydroxycryptotanshinone) exhibit high amounts of PARP protein cleavage, which is a hallmark of apoptosis [ 274 ].…”