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. 2022 May 5;27(9):2944.
doi: 10.3390/molecules27092944.

Inhibitory Effects and Mechanism of the Natural Compound Diaporthein B Extracted from Marine-Derived Fungi on Colon Cancer Cells

Peihua Tang  1   2 , Dandan Liu  1   2 , Zheli Wu  1   2 , Hui Cui  3 , Ren Zhang  1   2 , Zaoyuan Kuang  1   2
Affiliations

Inhibitory Effects and Mechanism of the Natural Compound Diaporthein B Extracted from Marine-Derived Fungi on Colon Cancer Cells

Peihua Tang et al. Molecules. .

Abstract

This study aimed to investigate the inhibitory effects and mechanism of diaporthein B (DTB), a natural compound extracted from the fungus Penicillium sclerotiorum GZU-XW03-2, on human colon cancer cells. The inhibitory effect of DTB at different concentrations on the proliferation of colon cancer cells HCT116 and LOVO was detected at 24 and 48 h. The effect of cell migration and clone formation ability were detected by cell scratch and plate cloning experiments. Morphological changes were observed by Hoechst 33342 and Annexin-V/PI staining, and flow cytometry was used to detect the proportion of apoptotic cells. DTB significantly inhibited colon cancer cell proliferation, migration, and apoptosis in a dose-dependent manner without significant effects on normal colonic epithelial cells NCM460. The IC50 inhibition effect can be achieved after treatment with 3 μmol/L DTB for 24 h. Compared with the blank group, the migration and clonal-forming ability of colon cancer cells in the DTB group was significantly decreased (p < 0.01), while the apoptotic cells were significantly increased (p < 0.01) in a concentration-dependent manner. DTB can inhibit the proliferation and migration of human colon cancer cells HCT116 and LOVO and promote the apoptosis of human colon cancer cells.

Keywords: DTB; Hippo; YAP; colon cancer; mitochondrial apoptosis pathway.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of 1–8; the chemical structure of DTB: C20H28O6, mass: 364.19.
Figure 2
Figure 2
(A) The 24 h dose–response curves of DTB on normal human intestinal epithelial cells NCM460. (B) The dose–response curves of DTB on HCT116 colon cancer cells for 24 and 48 h. (C) The dose-response curves of DTB on SW480 colon cancer cells for 24 and 48 h. (D) The dose-response curves of DTB on LOVO colon cancer cells for 24 and 48 h. The abscissa is the DTB concentration and the ordinate is the rate of cell inhibition with the blank control group as a reference. n = 4; each data point represents the mean ± standard error. Compared with the blank group, * p < 0.05, ** p < 0.01.
Figure 3
Figure 3
(A) The effect of DTB on colon cancer HCT116 and LOVO cells’ clone formation ability. The left is the blank control group, the middle is the DTB 1.5 μmol/L group, and the right is the DTB 3 μmol/L group. (B) Rate of clone formation. n = 3; each data point represents the mean ± standard error. Compared with the blank group, ** p < 0.01.
Figure 4
Figure 4
(A) The effect of different concentrations of DTB on the wound healing of HCT116 and LOVO cells under the microscope (×40). (B) The effect of DTB on the wound healing rate of colon cancer. n = 3; each data point represents the mean ± standard error. Compared with the blank group, ** p < 0.01.
Figure 5
Figure 5
Hoechst 33342 and PI staining to observe the effect of DTB on the apoptotic morphology of human colon cancer LOVO cells. The bright blue and red coloring can be seen at the place indicated by the yellow arrow.
Figure 6
Figure 6
(A) Flow cytometry to detect the apoptosis rate of colon cancer cells HCT116 and LOVO after DTB intervention. (Q1-UR: the late apoptotic cells; Q1-LR: the early apoptotic cells. The abscissa is Annexin V FITC staining, and the ordinate is PI staining.) (B) Flow cytometric detection of the apoptotic rate of colon cancer cells. n = 3; compared with the blank group, ** p < 0.01, each data point represents the mean ± standard deviation.
Figure 7
Figure 7
Changes in the expression of mitochondrial apoptosis-related genes BCL-2 and BAX in human normal intestinal epithelial cells NCM460 and colon cancer cells HCT116 and LOVO. n = 3; Compared with the blank group, ** p < 0.01, each data point represents the mean ± standard error.
Figure 8
Figure 8
The effect of DTB on the expression of mitochondrial-related genes BCL-2, BAX, and TP53 in colon cancer cells LOVO. n = 3; compared with the blank group, ** p < 0.01, each data point represents the mean ± standard error.
Figure 9
Figure 9
The effect of DTB on the expression of mitochondrial-related genes BCL-2, BAX, and TP53 in colon cancer cells HCT 116. n = 3; compared with the blank group, ** p < 0.01, each data point represents the mean ± standard error.
Figure 10
Figure 10
The effect of DTB on the expression of YAP and TAZ related genes of the HCT116 Hippo pathway in colon cancer cells. n = 3; compared with the blank group, ** p < 0.01, each data point represents the mean ± standard error.
Figure 11
Figure 11
The effect of DTB on the expression of YAP and TAZ related genes of the LOVO Hippo pathway in colon cancer cells. n = 3; compared with the blank group, ** p < 0.01, each data point represents the mean ± standard error.
Figure 12
Figure 12
Electrophoresis of Yaz and TAZ protein expression in colon cancer cells after DTB intervention.
Figure 13
Figure 13
Electrophoretic grayscale values of Yaz and TAZ protein expression in colon cancer cells after DTB intervention. n = 3; compared with the blank group, * p < 0.05; ** p < 0.01, each data point represents the mean ± standard error.
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