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Article

Anti-Warburg Mechanism of Ginsenoside F2 in Human Cervical Cancer Cells via Activation of miR193a-5p and Inhibition of β-Catenin/c-Myc/Hexokinase 2 Signaling Axis

by
Nari Shin
1,†,
Hyo-Jung Lee
1,†,
Deok Yong Sim
1,
Chi-Hoon Ahn
1,
Su-Yeon Park
1,
Wonil Koh
1,
Jaeho Khil
2,
Bum-Sang Shim
1,
Bonglee Kim
1 and
Sung-Hoon Kim
1,*
1
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
2
Institute of Sports Science, Kyung Hee University, Yongin 17104, Republic of Korea
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2024, 25(17), 9418; https://doi.org/10.3390/ijms25179418
Submission received: 8 July 2024 / Revised: 17 August 2024 / Accepted: 28 August 2024 / Published: 30 August 2024
(This article belongs to the Special Issue Effect of Plant Bioactives and Their Constituents on Human Cell Activity)
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Abstract

Though Ginsenoside F2 (GF2), a protopanaxadiol saponin from Panax ginseng, is known to have an anticancer effect, its underlying mechanism still remains unclear. In our model, the anti-glycolytic mechanism of GF2 was investigated in human cervical cancer cells in association with miR193a-5p and the β-catenin/c-Myc/Hexokinase 2 (HK2) signaling axis. Here, GF2 exerted significant cytotoxicity and antiproliferation activity, increased sub-G1, and attenuated the expression of pro-Poly (ADPribose) polymerase (pro-PARP) and pro-cysteine aspartyl-specific protease (procaspase3) in HeLa and SiHa cells. Consistently, GF2 attenuated the expression of Wnt, β-catenin, and c-Myc and their downstream target genes such as HK2, pyruvate kinase isozymes M2 (PKM2), and lactate dehydrogenase A (LDHA), along with a decreased production of glucose and lactate in HeLa and SiHa cells. Moreover, GF2 suppressed β-catenin and c-Myc stability in the presence and absence of cycloheximide in HeLa cells, respectively. Additionally, the depletion of β-catenin reduced the expression of c-Myc and HK2 in HeLa cells, while pyruvate treatment reversed the ability of GF2 to inhibit β-catenin, c-Myc, and PKM2 in GF2-treated HeLa cells. Notably, GF2 upregulated the expression of microRNA139a-5p (miR139a-5p) in HeLa cells. Consistently, the miR139a-5p mimic enhanced the suppression of β-catenin, c-Myc, and HK2, while the miR193a-5p inhibitor reversed the ability of GF2 to attenuate the expression of β-catenin, c-Myc, and HK2 in HeLa cells. Overall, these findings suggest that GF2 induces apoptosis via the activation of miR193a-5p and the inhibition of β-catenin/c-Myc/HK signaling in cervical cancer cells.
Keywords: ginsenoside F2; cervical cancer; apoptosis; glycolysis; miR193a-5p ginsenoside F2; cervical cancer; apoptosis; glycolysis; miR193a-5p

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MDPI and ACS Style

Shin, N.; Lee, H.-J.; Sim, D.Y.; Ahn, C.-H.; Park, S.-Y.; Koh, W.; Khil, J.; Shim, B.-S.; Kim, B.; Kim, S.-H. Anti-Warburg Mechanism of Ginsenoside F2 in Human Cervical Cancer Cells via Activation of miR193a-5p and Inhibition of β-Catenin/c-Myc/Hexokinase 2 Signaling Axis. Int. J. Mol. Sci. 2024, 25, 9418. https://doi.org/10.3390/ijms25179418

AMA Style

Shin N, Lee H-J, Sim DY, Ahn C-H, Park S-Y, Koh W, Khil J, Shim B-S, Kim B, Kim S-H. Anti-Warburg Mechanism of Ginsenoside F2 in Human Cervical Cancer Cells via Activation of miR193a-5p and Inhibition of β-Catenin/c-Myc/Hexokinase 2 Signaling Axis. International Journal of Molecular Sciences. 2024; 25(17):9418. https://doi.org/10.3390/ijms25179418

Chicago/Turabian Style

Shin, Nari, Hyo-Jung Lee, Deok Yong Sim, Chi-Hoon Ahn, Su-Yeon Park, Wonil Koh, Jaeho Khil, Bum-Sang Shim, Bonglee Kim, and Sung-Hoon Kim. 2024. "Anti-Warburg Mechanism of Ginsenoside F2 in Human Cervical Cancer Cells via Activation of miR193a-5p and Inhibition of β-Catenin/c-Myc/Hexokinase 2 Signaling Axis" International Journal of Molecular Sciences 25, no. 17: 9418. https://doi.org/10.3390/ijms25179418

APA Style

Shin, N., Lee, H.-J., Sim, D. Y., Ahn, C.-H., Park, S.-Y., Koh, W., Khil, J., Shim, B.-S., Kim, B., & Kim, S.-H. (2024). Anti-Warburg Mechanism of Ginsenoside F2 in Human Cervical Cancer Cells via Activation of miR193a-5p and Inhibition of β-Catenin/c-Myc/Hexokinase 2 Signaling Axis. International Journal of Molecular Sciences, 25(17), 9418. https://doi.org/10.3390/ijms25179418

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