Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Acetylcorynoline Induces Apoptosis and G2/M Phase Arrest through the c-Myc Signaling Pathway in Colon Cancer Cells

Version 1 : Received: 12 November 2023 / Approved: 13 November 2023 / Online: 13 November 2023 (10:11:10 CET)

A peer-reviewed article of this Preprint also exists.

Park, Y.-R.; Jee, W.; Park, S.-M.; Kim, S.-W.; Jung, J.-H.; Kim, H.; Kim, K.-I.; Jang, H.-J. Acetylcorynoline Induces Apoptosis and G2/M Phase Arrest through the c-Myc Signaling Pathway in Colon Cancer Cells. Int. J. Mol. Sci. 2023, 24, 17589. Park, Y.-R.; Jee, W.; Park, S.-M.; Kim, S.-W.; Jung, J.-H.; Kim, H.; Kim, K.-I.; Jang, H.-J. Acetylcorynoline Induces Apoptosis and G2/M Phase Arrest through the c-Myc Signaling Pathway in Colon Cancer Cells. Int. J. Mol. Sci. 2023, 24, 17589.

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose of 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrates that ACN inhibited c-Myc expression through CNOT2 and MID1IP1 and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.

Keywords

Acetylcorynoline; c-Myc; CNOT2; MID1IP1; Colon cancer

Subject

Biology and Life Sciences, Life Sciences

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