Leelamine Exerts Antineoplastic Effects in Association with Modulating Mitogen-Activated Protein Kinase Signaling Cascade

Mitogen-activated protein kinase (MAPK) pathway is a prominent signaling cascade that modulates cell proliferation, apoptosis, stress response, drug resistance, immune response, and cell motility. Activation of MAPK by various small molecules/natural compounds has been demonstrated to induce apoptos...

Full description

Saved in:
Bibliographic Details
Published inNutrition and cancer Vol. 74; no. 9; pp. 3375 - 3387
Main Authors Sin, Zi Wayne, Mohan, Chakrabhavi Dhananjaya, Chinnathambi, Arunachalam, Govindasamy, Chandramohan, Rangappa, Shobith, Rangappa, Kanchugarakoppal S., Jung, Young Yun, Ahn, Kwang Seok
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 13.08.2022
Taylor & Francis Ltd
Subjects
Apoptosis
Bark
Bcl-x protein
Breast cancer
Caspase-3
Cell activation
Cell proliferation
Cellular stress response
Cytotoxicity
Drug resistance
Extracellular signal-regulated kinase
Hepatocellular carcinoma
Immune response
Kinases
Liver cancer
MAP kinase
Motility
Phosphorylation
Pine trees
Protein kinase
Proteins
SDF-1 protein
Signaling
Toxicity
XIAP protein
Online AccessGet full text

Cover

More Information
Summary:Mitogen-activated protein kinase (MAPK) pathway is a prominent signaling cascade that modulates cell proliferation, apoptosis, stress response, drug resistance, immune response, and cell motility. Activation of MAPK by various small molecules/natural compounds has been demonstrated to induce apoptosis in cancer cells. Herein, the effect of leelamine (LEE, a triterpene derived from bark of pine trees) on the activation of MAPK in hepatocellular carcinoma (HCC) and breast cancer (BC) cells was investigated. LEE induced potent cytotoxicity of HCC (HepG2 and HCCLM3) and BC (MDA-MB-231 and MCF7) cells over normal counterparts (MCF10A). LEE significantly enhanced the phosphorylation of p38 and JNK MAPKs in a dose-dependent fashion and it did not affect the phosphorylation of ERK in HCC and BC cells. The apoptosis-driving effect of LEE was further demonstrated by cleavage of procaspase-3/Bid and suppression of prosurvival proteins (Bcl-xL and XIAP). Furthermore, LEE also reduced the SDF1-induced-migration and -invasion of HCC and BC cells. Taken together, the data demonstrated that LEE promotes apoptosis and induces an anti-motility effect by activating p38 and JNK MAPKs in HCC and BC cells.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0163-5581
1532-7914
DOI:10.1080/01635581.2022.2059092