Two Natural Alkaloids Synergistically Induce Apoptosis in Breast Cancer Cells by Inhibiting STAT3 Activation

Breast cancer has become a worldwide threat, and chemotherapy remains a routine treatment. Patients are forced to receive continuous chemotherapy and suffer from severe side effects and poor prognosis. Natural alkaloids, such as piperine (PP) and piperlongumine (PL), are expected to become a new str...

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Bibliographic Details
Published in:	Molecules (Basel, Switzerland) Vol. 25; no. 1; p. 216
Main Authors:	Chen, Di, Ma, Yangmin, Guo, Zhiyu, Liu, Li, Yang, Yaru, Wang, Yuru, Pan, Bonan, Wu, Luyang, Hui, Yuyu, Yang, Wenjuan
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 05-01-2020 MDPI
Subjects:	Alkaloids Alkaloids - pharmacology Apoptosis Apoptosis - drug effects Benzodioxoles - pharmacology Breast cancer Breast Neoplasms - metabolism Cancer therapies Cell activation Cell cycle Cell growth Cell Line, Tumor Cell proliferation Cell Proliferation - drug effects Cell Survival - drug effects Cell viability Chemotherapy Dioxolanes - pharmacology Drug dosages Drug resistance Female Flow cytometry Humans Inactivation Kinases MCF-7 Cells Medical prognosis Phosphorylation Phosphorylation - drug effects Piperidines - pharmacology Piperine piperlongumine Polyunsaturated Alkamides - pharmacology Proteins Selectivity Signal transduction Signal Transduction - drug effects stat3 Stat3 protein STAT3 Transcription Factor - metabolism apoptosis breast cancer piperine piperlongumine STAT3
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Summary:	Breast cancer has become a worldwide threat, and chemotherapy remains a routine treatment. Patients are forced to receive continuous chemotherapy and suffer from severe side effects and poor prognosis. Natural alkaloids, such as piperine (PP) and piperlongumine (PL), are expected to become a new strategy against breast cancer due to their reliable anticancer potential. In the present study, cell viability, flow cytometry, and Western blot assays were performed to evaluate the suppression effect of PP and PL, alone or in combination. Data showed that PP and PL synergistically inhibited breast cancer cells proliferation at lower doses, while only weak killing effect was observed in normal breast cells, indicating a good selectivity. Furthermore, apoptosis and STAT3 signaling pathway-associated protein levels were analyzed. We demonstrated that PP and PL in combination inhibit STAT3 phosphorylation and regulate downstream molecules to induce apoptosis in breast cancer cells. Taken together, these results revealed that inactivation of STAT3 was a novel mechanism with treatment of PP and PL, suggesting that combination application of natural alkaloids may be a potential strategy for prevention and therapy of breast cancer.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1420-3049 1420-3049
DOI:	10.3390/molecules25010216