Proliferation Inhibitory Activity of Quinones from Blaps rynchopetera Defense Secretion on Colorectal Tumor Cells

Xiao-Li Qian; Di Meng; Heng Liu; Chao-He Liu; Ping Zhou; Yin-He Yang; Jia-Peng Wang; Huai Xiao; Zhong-Tao Ding

doi:10.1007/s11655-023-3696-y

Proliferation Inhibitory Activity of Quinones from Blaps rynchopetera Defense Secretion on Colorectal Tumor Cells

Chin J Integr Med. 2023 Aug;29(8):683-690. doi: 10.1007/s11655-023-3696-y. Epub 2023 Apr 18.

Authors

Xiao-Li Qian^{1

2}, Di Meng^{1

2}, Heng Liu^{1

2}, Chao-He Liu^{1

2}, Ping Zhou², Yin-He Yang^{1

2}, Jia-Peng Wang^{1

2}, Huai Xiao^{3

4}, Zhong-Tao Ding⁵

Affiliations

¹ Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali, Yunnan Province, 671003, China.
² College of Pharmacy, Dali University, Dali, Yunnan Province, 671003, China.
³ Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali, Yunnan Province, 671003, China. xiaohuai@dali.edu.cn.
⁴ College of Pharmacy, Dali University, Dali, Yunnan Province, 671003, China. xiaohuai@dali.edu.cn.
⁵ Functional Molecules Analysis and Biotransformation Key Laboratory of Universities in Yunnan Province, Kunming, 650091, China.

PMID: 37071326
DOI: 10.1007/s11655-023-3696-y

Abstract

Objective: To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines.

Methods: Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively.

Results: MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC₅₀) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC₅₀ values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC₅₀ values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G₁ phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3β and APC, while down-regulate that of β-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/β-catenin pathway of HT-29 cells.

Conclusion: Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/β-catenin pathway-related mRNA and protein expressions.

Keywords: Blaps rynchopetera; Chinese medicine; Wnt/β-catenin pathway; anti-colorectal tumor; quinones.

MeSH terms

Apoptosis
Benzoquinones / pharmacology
Caco-2 Cells
Cell Line, Tumor
Cell Proliferation
Colorectal Neoplasms* / drug therapy
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / metabolism
Glycogen Synthase Kinase 3 beta / metabolism
Humans
Quinones / pharmacology
RNA, Messenger
Wnt Signaling Pathway
beta Catenin* / metabolism

Substances

beta Catenin
Quinones
Glycogen Synthase Kinase 3 beta
quinone
Benzoquinones
2-methyl-1,4-benzoquinone
RNA, Messenger