Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways
Breast cancer is the most commonly diagnosed cancer in females worldwide. Estimates from the World Health Organization (WHO) International Agency for Research on Cancer, suggest that globally, there were around 2.1 million new breast cancer cases and 627,000 deaths due to breast cancer in 2018. Amon...
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Frontiers Media S.A.
2020-04-01
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Series: | Frontiers in Oncology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00491/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Magnolia Muk-Lan Lee Brandon Dow Chan Wing-Yan Wong Zhao Qu Man-Sum Chan Tsz-Wing Leung Yushan Lin Daniel Kam-Wah Mok Daniel Kam-Wah Mok Sibao Chen Sibao Chen Sibao Chen William Chi-Shing Tai William Chi-Shing Tai |
spellingShingle |
Magnolia Muk-Lan Lee Brandon Dow Chan Wing-Yan Wong Zhao Qu Man-Sum Chan Tsz-Wing Leung Yushan Lin Daniel Kam-Wah Mok Daniel Kam-Wah Mok Sibao Chen Sibao Chen Sibao Chen William Chi-Shing Tai William Chi-Shing Tai Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways Frontiers in Oncology Centipeda minima natural compounds breast cancer triple negative breast cancer (TNBC) anti-cancer |
author_facet |
Magnolia Muk-Lan Lee Brandon Dow Chan Wing-Yan Wong Zhao Qu Man-Sum Chan Tsz-Wing Leung Yushan Lin Daniel Kam-Wah Mok Daniel Kam-Wah Mok Sibao Chen Sibao Chen Sibao Chen William Chi-Shing Tai William Chi-Shing Tai |
author_sort |
Magnolia Muk-Lan Lee |
title |
Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways |
title_short |
Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways |
title_full |
Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways |
title_fullStr |
Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways |
title_full_unstemmed |
Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways |
title_sort |
anti-cancer activity of centipeda minima extract in triple negative breast cancer via inhibition of akt, nf-κb, and stat3 signaling pathways |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2020-04-01 |
description |
Breast cancer is the most commonly diagnosed cancer in females worldwide. Estimates from the World Health Organization (WHO) International Agency for Research on Cancer, suggest that globally, there were around 2.1 million new breast cancer cases and 627,000 deaths due to breast cancer in 2018. Among the subtypes of breast cancer, triple negative breast cancer (TNBC) is the most aggressive and carries the poorest prognosis, largest recurrence, and lowest survival rate. Major treatment options for TNBC patients are mainly constrained to chemotherapy, which can be accompanied by severe side effects. Therefore, development of novel and effective anti-cancer drugs for the treatment of TNBC are urgently required. Centipeda minima is a well-known traditional Chinese herbal medicine that has historically been used to treat rhinitis, sinusitis, relieve pain, and reduce swelling. Recent studies have shown that Centipeda minima exhibited efficacy against certain cancers, however, to date, no studies have been conducted on its effects in breast cancer. Here, we aimed to investigate the anti-cancer activity of the total extract of Centipeda minima (CME), and its underlying mechanism, in TNBC. In MDA-MB-231, we found that CME could significantly reduce cell viability and proliferation, induce apoptosis and inhibit cancer cell migration and invasion, in a dose and time-dependent manner. We showed that CME may potentially act via inhibition of multiple signaling pathways, including the EGFR, PI3K/AKT/mTOR, NF-κB, and STAT3 pathways. Treatment with CME also led to in vitro downregulation of MMP-9 activity and inhibition of metastasis. Further, we demonstrated that CME could significantly reduce tumor burden in MDA-MB-231 xenograft mice, without any appreciable side effects. Based on our findings, CME is a promising candidate for development as a therapeutic with high efficacy against TNBC. |
topic |
Centipeda minima natural compounds breast cancer triple negative breast cancer (TNBC) anti-cancer |
url |
https://www.frontiersin.org/article/10.3389/fonc.2020.00491/full |
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doaj-7379ce27a1484bf7be92dc0f5e6091e82020-11-25T02:41:52ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-04-011010.3389/fonc.2020.00491506242Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling PathwaysMagnolia Muk-Lan Lee0Brandon Dow Chan1Wing-Yan Wong2Zhao Qu3Man-Sum Chan4Tsz-Wing Leung5Yushan Lin6Daniel Kam-Wah Mok7Daniel Kam-Wah Mok8Sibao Chen9Sibao Chen10Sibao Chen11William Chi-Shing Tai12William Chi-Shing Tai13Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, ChinaDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, ChinaDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, ChinaState Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, ChinaDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, ChinaDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, ChinaState Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, ChinaDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, ChinaState Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, ChinaDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, ChinaState Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, ChinaState Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, ChinaBreast cancer is the most commonly diagnosed cancer in females worldwide. Estimates from the World Health Organization (WHO) International Agency for Research on Cancer, suggest that globally, there were around 2.1 million new breast cancer cases and 627,000 deaths due to breast cancer in 2018. Among the subtypes of breast cancer, triple negative breast cancer (TNBC) is the most aggressive and carries the poorest prognosis, largest recurrence, and lowest survival rate. Major treatment options for TNBC patients are mainly constrained to chemotherapy, which can be accompanied by severe side effects. Therefore, development of novel and effective anti-cancer drugs for the treatment of TNBC are urgently required. Centipeda minima is a well-known traditional Chinese herbal medicine that has historically been used to treat rhinitis, sinusitis, relieve pain, and reduce swelling. Recent studies have shown that Centipeda minima exhibited efficacy against certain cancers, however, to date, no studies have been conducted on its effects in breast cancer. Here, we aimed to investigate the anti-cancer activity of the total extract of Centipeda minima (CME), and its underlying mechanism, in TNBC. In MDA-MB-231, we found that CME could significantly reduce cell viability and proliferation, induce apoptosis and inhibit cancer cell migration and invasion, in a dose and time-dependent manner. We showed that CME may potentially act via inhibition of multiple signaling pathways, including the EGFR, PI3K/AKT/mTOR, NF-κB, and STAT3 pathways. Treatment with CME also led to in vitro downregulation of MMP-9 activity and inhibition of metastasis. Further, we demonstrated that CME could significantly reduce tumor burden in MDA-MB-231 xenograft mice, without any appreciable side effects. Based on our findings, CME is a promising candidate for development as a therapeutic with high efficacy against TNBC.https://www.frontiersin.org/article/10.3389/fonc.2020.00491/fullCentipeda minimanatural compoundsbreast cancertriple negative breast cancer (TNBC)anti-cancer |