Antiproliferative activities of Euphorbia bicolor (euphorbiaceae) and Maclura pomifera (moraceae) extracts on estrogen receptor-positive and triple-negative breast cancer cell lines

Breast cancer remains a leading cause of mortality worldwide, driving the search for novel therapeutic compounds. Recent research has highlighted the transient receptor potential vanilloid 1 (TRPV1) ion channel as a promising target for cancer treatment. This study explores the antiproliferative properties and mechanisms of action of phytochemicals from two native plants, Maclura pomifera and Euphorbia bicolor, in breast cancer cell lines. Maclura pomifera, a dioecious tree native to the south-central USA, showed significant antiproliferative effects in estrogen receptor positive MCF-7 and T47D breast cancer cells. Extracts of both male and female branches and leaves (500 µg/mL) reduced cancer cell viability by 75–80%. These effects were mediated by intracellular calcium overload via TRPV1 activation, leading to apoptosis. Blocking TRPV1 with capsazepine and using the calcium chelator BAPTA-AM rescued cell viability, confirming the role of TRPV1. The extracts activated multiple apoptotic pathways, including mitochondrial, ERK-induced, and endoplasmic reticulum stress-mediated apoptotic mechanisms. Key apoptotic markers such as caspase 3, caspase 8, caspase 9, FADD, FAS, ATF4, and CHOP were upregulated, while antiapoptotic BCL-2 expression was downregulated. Notably, the female extract also inhibited the PI3K/AKT pathway by reducing AKT and pAKT protein levels. Euphorbia bicolor diterpene extracts demonstrated antiproliferative effects in estrogen receptor-positive T47D and triple-negative MDA-MB-231 breast cancer cells. In MDA-MB-231 cells, apoptosis was induced through TRPV1-mediated calcium overload, similarly to M. pomifera extracts. However, in T47D cells, apoptosis was driven by a 10-fold increase in reactive oxygen species (ROS) than in MDA-MB-231 cells. Both cell lines showed disruption of calcium homeostasis, leading to mitochondrial and ER stress, activating apoptotic markers caspase 3, caspase 9, caspase 8, FAS, XBP1s, CHOP, and BAX, and reducing BCL-2 levels. PI3K/AKT pathway inhibition was observed in both cell lines. These findings suggest that Maclura pomifera and Euphorbia bicolor phytochemicals could be promising candidates for breast cancer therapeutics by modulating TRPV1 activity and inducing apoptosis through multiple apoptotic pathways.

Name thesis:degree_name

Doctor of Philosophy

Discipline thesis:degree_discipline

Molecular Biology

Grantor

Texas Woman's University

Year dc:date.issued

2024

Author dc:creator

• Rumpa, Mafia Mahabub

Advisor dc:contributor.advisor

• Maier, Camelia

Committee members dc:contributor.committeemember

• Pislariu, Catalina
• Bergel, Michael
• Juma, Shanil
• Averitt, Dayna L

• ER-dependent apoptosis
• Extrinsic apoptotic pathway
• Mitochondrial intrinsic apoptotic pathway
• Apoptosis
• ER-positive
• Euphorbia bicolor
• Dioecious Maclura pomifera
• TRPV1
• Breast cancer

Handle dc:identifier.uri

https://hdl.handle.net/11274/16877

OAI identifier oai:identifier

oai:twu-ir.tdl.org:11274/16877