2. Academic Validation
  3. Chinese medicine formula 'Baipuhuang Keli' inhibits triple-negative breast cancer by hindering DNA damage repair via MAPK/ERK pathway

Chinese medicine formula 'Baipuhuang Keli' inhibits triple-negative breast cancer by hindering DNA damage repair via MAPK/ERK pathway

  • J Ethnopharmacol. 2022 Dec 24;304:116077. doi: 10.1016/j.jep.2022.116077.
Shichao Mi 1,  Xin Liu 2,  Liufeng Zhang 1,  Yifan Wang 1,  Li Sun 1,  Shengtao Yuan 1,  Min Cui 3,  Yanyan Liu 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
  • 2 Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affliated with Jinan University, Zhuhai, Guangdong, China.
  • 3 Department of General Surgery, Zhuhai People's Hospital, Zhuhai Hospital Affliated with Jinan University, Zhuhai, Guangdong, China. Electronic address: [email protected].
  • 4 Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affliated with Jinan University, Zhuhai, Guangdong, China. Electronic address: [email protected].
PMID: 36572327 DOI: 10.1016/j.jep.2022.116077
Abstract

Ethnopharmacological relevance: Baipuhuang Keli (BPH, constituted by Bai Tou Weng (Pulsatilla chinensis (Bunge) Regel), Pu Gong Ying (Taraxacum mongolicum Hand.-Mazz.), Huang Qin (Scutellaria baicalensis Georgi), Huang Bo (Phellodendron amurense Rupr.)) is a Chinese herbal formula with clearing heat and cooling blood, and removing toxin effects, which is suit for the case of breast Cancer.

Aim of the study: Here, we aim to explore the effects of BPH on triple-negative breast Cancer (TNBC) and its potential mechanisms.

Materials and methods: In this study, cell viability assay, colony formation assay, soft agar assay, cell proliferation curve assay, and EdU assay were employed to determine the anti-proliferation effect induced by BPH. Cell cycle distribution was detected by flow cytometry. DNA damage in cells treated with BPH was indicated by comet assay, immunofluorescence, and Western Blot. Both the 4T1 orthotopic tumor model and the MDA-MB-231 subcutaneous tumor model were used to assess in vivo effect of BPH (312.5, and 625 mg/kg). The protein expression levels of the DNA damage response (DDR) pathway and the MAPK/ERK pathway were detected by Western Blot.

Results: Our results indicated that TNBC cells were more sensitive to BPH than mammary epithelial cells. Cell proliferation of TNBC cells was significantly inhibited by BPH in a dose-dependent manner. Moreover, BPH induced DNA damage in TNBC cells in a concentration and time-dependent manner. DDR of TNBC cells was inhibited by BPH. MAPK/ERK pathway was inhibited in cells treated with BPH, and DNA damage can be reversed while EGF was added to activate MAPK/ERK pathway. The 4T1 orthotopic tumor model and the MDA-MB-231 subcutaneous tumor model further confirmed that BPH inhibited TNBC proliferation via inhibition of DDR and MAPK/ERK pathway in vivo.

Conclusions: Collectively, we proved that BPH is a potential Anticancer Chinese herbal formula for TNBC in the manner of in vitro and in vivo experiments.

Keywords

Baipuhuang Keli; Cell proliferation; DNA Damage response; MAPK/ERK pathway; Triple-negative breast cancer.

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