Chrysophanol inhibits of colorectal cancer cell motility and energy metabolism by targeting the KITENIN/ErbB4 oncogenic complex.

Varli, Mücahit; Kim, Eunae; Oh, Songjin; Pulat, Sultan; Zhou, Rui; Gamage, Chathurika D B; Gökalsin, Baris; Sesal, Nüzhet Cenk; Kim, Kyung Keun; Paik, Man-Jeong; Kim, Hangun

Varli, Mücahit; Kim, Eunae; Oh, Songjin; Pulat, Sultan; Zhou, Rui; Gamage, Chathurika D B; Gökalsin, Baris; Sesal, Nüzhet Cenk; Kim, Kyung Keun; Paik, Man-Jeong; Kim, Hangun.

Afiliación

Varli M; College of Pharmacy, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam, 57922, Republic of Korea.
Kim E; College of Pharmacy, Chosun University, 146 Chosundae-gil, Gwangju, 61452, Republic of Korea.
Oh S; College of Pharmacy, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam, 57922, Republic of Korea.
Pulat S; College of Pharmacy, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam, 57922, Republic of Korea.
Zhou R; College of Pharmacy, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam, 57922, Republic of Korea.
Gamage CDB; College of Pharmacy, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam, 57922, Republic of Korea.
Gökalsin B; Faculty of Arts and Sciences, Department of Biology, Marmara University, Istanbul, Türkiye.
Sesal NC; Faculty of Arts and Sciences, Department of Biology, Marmara University, Istanbul, Türkiye.
Kim KK; Department of Pharmacology, Chonnam National University Medical School, 160 Baekseoro, Gwangju, 61469, Republic of Korea.
Paik MJ; College of Pharmacy, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam, 57922, Republic of Korea.
Kim H; College of Pharmacy, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam, 57922, Republic of Korea. hangunkim@scnu.ac.kr.

Cancer Cell Int ; 24(1): 253, 2024 Jul 20.

Article en En | MEDLINE | ID: mdl-39030594

ABSTRACT

ABSTRACT

BACKGROUND:

Expression of the KITENIN/ErbB4 oncogenic complex is associated with metastasis of colorectal cancer to distant organs and lymph nodes and is linked with poor prognosis and poor survival.

METHODS:

Here, we used in vitro and in silico methods to test the ability of chrysophanol, a molecule of natural origin, to suppress the progression of colorectal cancer by targeting the KITENIN/ErbB4 complex.

RESULTS:

Chrysophanol binds to ErbB4, disrupting the ErbB4/KITENIN complex and causing autophagic degradation of KITENIN. We demonstrated that chrysophanol binds to ErbB4 according to a molecular docking model. Chrysophanol reversed KITENIN-mediated effects on cell motility, aerobic glycolysis, and expression of downstream effector genes. Moreover, under conditions of KITENIN overexpression, chrysophanol suppressed the production of onco-metabolites.