TRPV1-Dependent Antiproliferative Activity of Dioecious Maclura pomifera Extracts in Estrogen Receptor-Positive Breast Cancer Cell Lines Involves Multiple Apoptotic Pathways.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Apoptosis*/drug effects ; TRPV Cation Channels*/metabolism ; Plant Extracts*/pharmacology ; Plant Extracts*/chemistry ; Breast Neoplasms*/metabolism ; Breast Neoplasms*/drug therapy ; Breast Neoplasms*/pathology ; Cell Proliferation*/drug effects ; Receptors, Estrogen*/metabolism; Humans ; Female ; Cell Line, Tumor ; MCF-7 Cells ; Signal Transduction/drug effects ; Cell Survival/drug effects

Globally, breast cancer is a significant cause of mortality. Recent research focused on identifying compounds regulating the transient receptor potential vanilloid 1 (TRPV1) ion channel activity for the possibility of developing cancer therapeutics. In this study, the antiproliferative properties and mechanisms of action through TRPV1 of Maclura pomifera , a dioecious tree native to the south-central USA, have been investigated. Male and female extracts of spring branch tissues and leaves (500 µg/mL) significantly reduced the viability of MCF-7 and T47D cells by 75-80%. M. pomifera extracts induced apoptosis by triggering intracellular calcium overload via TRPV1. Blocking TRPV1 with the capsazepine antagonist and pretreating cells with the BAPTA-AM chelator boosted cell viability, revealing that M. pomifera phytochemicals activate TRPV1. Both male and female M. pomifera extracts initiated apoptosis through multiple pathways, the mitochondrial, ERK-induced, and endoplasmic reticulum-stress-mediated apoptotic pathways, demonstrated by the expression of activated caspase 3, caspase 9, caspase 8, FADD, FAS, ATF4, and CHOP, the overexpression of phosphorylated PERK and ERK proteins, and the reduction of BCL-2 levels. In addition, AKT and pAKT protein expressions were reduced in female M. pomifera -treated cells, revealing that female plant extract also inhibits PI3K/Akt signaling pathways. These results suggest that phytochemicals in M. pomifera extracts could be promising for developing breast cancer therapeutics.

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Keywords: ER-dependent apoptosis; ER-positive breast cancer; TRPV1; apoptosis; breast cancer; dioecious Maclura pomifera; extrinsic apoptotic pathway; mitochondrial intrinsic apoptotic pathway

0 (TRPV Cation Channels)
0 (Plant Extracts)
0 (Receptors, Estrogen)
0 (TRPV1 protein, human)

Date Created: 20240525 Date Completed: 20240525 Latest Revision: 20240703

20240703

PMC11120667

10.3390/ijms25105258

38791297