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. 2022 Sep 27:2022:9358583.
doi: 10.1155/2022/9358583. eCollection 2022.

Transgelin-2 Involves in the Apoptosis of Colorectal Cancer Cells Induced by Tanshinone-IIA

Yingru Zhang #  1   2 , Yiyang Zhao #  1   2 , Jingwen Liu  1 , Chunpu Li  1 , Ying Feng  2 , Shasha Jiang  1   2 , Xiaoting Sun  1   2 , Xueqing Hu  1   2 , Yan Wang  1   2
Affiliations

Transgelin-2 Involves in the Apoptosis of Colorectal Cancer Cells Induced by Tanshinone-IIA

Yingru Zhang et al. Anal Cell Pathol (Amst). .

Abstract

Tanshinone IIA (TanIIA) is the main active ingredient in the fat-soluble components isolated from Salvia miltiorrhiza Bunge. Our previous studies have convincingly proved that TanIIA is an effective drug against human colorectal carcinoma cells. In order to further demonstrate the effect of TanIIA on CRC, we carried out exploratory research about it in vivo and in vitro. The results demonstrated that TanIIA were observably more effective than control group in preventing tumor growth, and it has increased the survival time. Cancer cells viability and proliferation were accompanied by concentration and time dependent decline reached with TanIIA. We found that TanIIA altered the morphology of cytoskeleton and it could obviously induce apoptosis of colorectal cancer cells and block the cells in the G0/G1 phase. TanIIA also increased phosphorylation of p38MAPK, upregulated ATF-2 expression and downregulated Transgelin-2 expression, which could be reversed by SB203580, a p38MAPK-specific inhibitor. Our results suggested that TanIIA could induce apoptosis of colorectal cancer and block the cells in G0/G1 phase involved in downregulating the expression of Transgelin-2 through p38MAPK signal pathway.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Figure 1
Figure 1
TanIIA inhibited the growth and proliferation of human colorectal cancer cell in vitro. (a) Tumor photos were taken from tumor-bearing nude mice after intravenous injection of normal saline, DMSO and TanIIA with 0.5 mg/kg, 1 mg/kg, 2 mg/kg for 2 weeks, respectively, and measured the volume (b) and the weight (c) of tumor. (d) Survival time of tumor-bearing nude mice compared with normal saline group after different treatment, ∗∗P < 0.01, ∗∗∗P < 0.001. (e) TUNEL assay was detected the degree of cell apoptosis in tumor-bearing nude mice, terminal deoxynucleotidyl transferase (green) bound to expose 3′-OH ends of DNA fragments generated. Apoptotic cells (TUNEL-positive cells) exhibit green fluorescence, and DAPI (blue fluorescence) stands for nucleus.
Figure 2
Figure 2
Effects of TanIIA on SW620 cell growth and proliferation. (a) Cell viability was evaluated by CCK assay after exposure to the 0, 2, 4, 8, 16, 32, and 64 μmol/L concentrations of TanIIA for 24, 48, and 72 h. (b) The median inhibitory concentration (IC50) at 24, 48, and 72 h was 41.60, 11.76, and 5.289 μmol/L, respectively, ∗∗P < 0.01, compared with 24 h. (c, d) The ability of cell proliferation was detected after TanIIA treatment by colony formation assay. ∗∗∗ P < 0.001, compared with control group.
Figure 3
Figure 3
Morphological changes of SW620 cells induced by TanIIA. After cells treated by different concentrations of TanIIA (4 umol, 8 umol, and 16 umol), cell nucleus stained with Hoechst 33258 (a) and cytoskeleton labeled with phalloidine (b).
Figure 4
Figure 4
Apoptosis induced by TanIIA in SW620 cells. (a) Effects of TanIIA on early apoptotic events and late apoptotic/necrotic events of SW620 cells after treated with SB203580, TanIIA (4 umol/L), TanIIA (8 umol/L), TanIIA (16 umol/L), and TanIIA (8 umol/L) + SB203580 for 48 h. (b) The cell cycle percentage was evaluated by FACS, ∗∗P < 0.01.
Figure 5
Figure 5
Effect of p38MAPK and ATF-2 expression in TanIIA induced- SW620 cells. Western blotting was used to ensure equal loading of proteins in each lane. (a–d) The ratio of p-p38MAPK, p38MAPK, ATF-2, and Transgelin-2 to GAPDH was calculated and expressed relative to that of control groups. (e, f) The expression of Bcl-2 and Bax was detected after different treatment (control, SB203580, TanIIA, and TanIIA+SB203580) of SW620 cells. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0, 001compared with control group. ###P < 0.001, compared with TanIIA (8 umol/L) group.
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