Brazilin Isolated fromCaesalpinia sappanSuppresses Nuclear Envelope Reassembly by Inhibiting Barrier-to-Autointegration Factor Phosphorylation

Abstract

To date, many anticancer drugs have been developed by directly or indirectly targeting microtubules, which are involved in cell division. Although this approach has yielded many anticancer drugs, these drugs produce undesirable side effects. An alternative strategy is needed, and targeting mitotic exit may be one alternative approach. Localization of phosphorylated barrierto-autointegration factor (BAF) to the chromosomal core region is essential for nuclear envelope compartment relocalization. In this study, we isolated brazilin from Caesalpinia sappan Leguminosae and demonstrated that it inhibited BAF phosphorylation in vitro and in vivo. Moreover, we demonstrated direct binding between brazilin and BAF. The inhibition of BAF phosphorylation induced abnormal nuclear envelope reassembly and cell death, indicating that perturbation of nuclear envelope reassembly could be a novel approach to anticancer therapy. We propose that brazilin isolated from C. sappan may be a new anticancer drug candidate that induces cell death by inhibiting vaccinia-related kinase 1-mediated BAF phosphorylation.

Comparative Interactomes of VRK1 and VRK3 with Their Distinct Roles in the Cell Cycle of Liver Cancer

“…After incubated with the secondary antibody for 2 h, immunocomplexes were detected by use of the femto, Pico or ECL reagent (Thermo). Antibodies for Western blotting are from the companies as follows: mouse/rabbit anti-flag antibody (Sigma), mouse anti-VRK1 (Santa Cruz), rabbit anti-VRK3 (Sigma), mouse ant-ALY antibody (Santa Cruz), rabbit anti-hsp70 (Origene), rabbit anti-XRCC5 (Santa Cruz), rabbit anti-B23 antibody (Santa Cruz), rabbit anti-C23 antibody (Santa Cruz), rabbit anti-PARP1 antibody (Cell signaling), rabbit anti-cyclin B1 (Santa Cruz), rabbit anti-p53 (Cell signaling) and rabbit anti-BAF [previously used (Kim et al, 2015)].…”

Caesalpanins A–C, Three Dimeric Cassane Diterpenoids from the Seeds of Caesalpinia sappan L.

“…[16] Detailed analysis of the 1 H-and 13 C-NMR spectroscopic data of unit 1a indicated that its structure was similar to that of caesanine B, [16] apart from the appearance of a hemiaminal moiety (δ(H) 5.11 (s, HÀ C(19)), δ(C) 89.6 (C(19))) in 1a instead of a methylene group connected to nitrogen atom in the latter. The hemiaminal moiety at C (19) was verified by the HMBCs (Figure 2) of HÀ C(19) with C(3) (δ(C) 31.1), C (18), and C (20). Furthermore, the key 1 H, 1 H-COSY and HMBCs as shown in Figure 2 allowed us to confirm the gross structure of unit 1a.…”

“…[14] This plant has been reported to contain phenolic components and cassane diterpenoids with a broad spectrum of antimalarial, antiproliferative, antimicrobial, and anti-inflammatory activities. [15][16][17][18][19][20] In our previous study, six new cassane diterpenoids were obtained from the seeds of C. sappan. [21] In order to further discover bioactive cassane diterpenoids from C. sappan, a 95 % EtOH extract of the seeds of this species was investigated, which led to the isolation of three dimeric cassane diterpenoids, caesalpanins A-C (1 -3), together with three known compounds (4 -6; Figure 1).…”

Contact dermatitis caused by brazilin in Caesalpinia sappan

“…Various compounds have been identified, such as brazilin, protosappanin, homoisoflavonoids, and chalcones. One of the main compounds in C. sappan , brazilin, is a reddish dye, and is claimed to have immunological activity .…”

“…Various compounds have been identified, such as brazilin, protosappanin, homoisoflavonoids, and chalcones. One of the main compounds in C. sappan, brazilin, is a reddish dye, and is claimed to have immunological activity (5). In this case, C. sappan and brazilin turned out as contact allergens, and elicited allergic contact dermatitis when applied as a water decoction.…”