Growth-inhibitory and apoptosis-inducing effects of tanshinones on hematological malignancy cells and their structure–activity relationship

Abstract

This study has investigated the growth-inhibitory and apoptosis-inducing effects of dihydrotanshinone, tanshinone I, tanshinone IIA, and cryptotanshinone on hematological malignancy cell lines, aiming to explore their structure-activity relationship. The growth-inhibitory effects of the tanshinones on K562 and Raji cells were assessed using a modified MTT assay; the apoptosis-inducing effects were assessed by fluorescence microscopy and flow cytometry analysis. The changes in cellular morphology were observed using an inverted phase-contrast microscope. MTT results revealed that these tanshinones inhibited cell proliferation in a concentration-dependent and time-dependent manner. The IC50 values of dihydrotanshinone, tanshinone I, tanshinone IIA, and cryptotanshinone for K562 cells were 3.50, 13.52, 19.32, and 47.52 μmol/l at 24 h; 1.36, 4.70, 5.67, and 22.72 μmol/l at 48 h; and 1.15, 1.59, 2.82, and 19.53 μmol/l at 72 h, and the values for Raji cells were 3.30, 4.37, 12.92, and 52.36 μmol/l at 24 h; 1.55, 1.71, 6.54, and 25.45 μmol/l at 48 h; and 1.07, 1.38, 1.89, and 18.47 μmol/l at 72 h. The flow cytometry analysis demonstrated that these tanshinones induced apoptosis of K562 cells in a concentration-dependent manner, and dihydrotanshinone as well as tanshinone I were more potent than tanshinone IIA and cryptotanshinone. Some noticeable apoptotic morphologies could be observed by fluorescence microscopy on tanshinones-treated Raji cells. Collectively, these tanshinones caused growth inhibition and apoptosis in hematological malignancy cell lines, with dihydrotanshinone being the most potent, followed by tanshinone I, tanshinone IIA, and cryptotanshinone. These results suggested that the structure of aromatic ring A enhanced the cytotoxicity and the structure of ring C may have contributed to the cytotoxicity, but the mechanisms need to be further investigated.

Cytotoxic effects of solvent-extracted active components of Salvia miltiorrhiza Bunge on human cancer cell lines

“…In the present study, dihydrotanshinone I exhibited the most notable cytotoxicity against the human cancer cell lines, followed by tanshinone I and cryptotanshinone. These results are consistent with previous reports, which indicated that dihydrotanshinone I possesses the most marked cytotoxic effect among the three tanshinones examined in numerous human cancer cell lines ( 14 , 29 , 30 ). As these three tanshinones possess similar chemical structures, the limited variations in these structures may be responsible for the differences in their cytotoxic effects.…”

“…As presented in Fig. 3B , the only structural differences among the three reference tanshinones are in aromatic rings A and C. A previous report indicated that the structure of ring A may contribute to the cytotoxic effect, resulting in the increased cytotoxic potential of dihydrotanshinone I and tanshinone I compared with cryptotanshinone, in terms of growth inhibition ( 29 ).…”

Signal transducer and activators of transcription 3 regulates cryptotanshinone-induced apoptosis in human mucoepidermoid carcinoma cells

“…In agreement with our present study, other group also reported that CT treatment induced programmed cell death in various cancer cell lines. [ 11 16 17 ] These results suggest that CT can be a good inducer of apoptosis in cancer cells.…”

Discovery and characterization of natural products as novel indoleamine 2,3-dioxygenase 1 inhibitors through high-throughput screening

“…Compound 7 is shikonin from Radix Arnebiae and was reported to possess anti-inflammatory activity [ 25 ]. Compound 8 is dihydrotanshinone I from Radix Salviae Miltiorrhizae and shows cytotoxicity against many types of cancer cells [ 26 ].

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