Berberine induces oxidative DNA damage and impairs homologous recombination repair in ovarian cancer cells to confer increased sensitivity to PARP inhibition

Hou, Dong; Xu, Guangwei; Zhang, Caibo; Li, Boxuan; Qin, Junchao; Hao, Xiaohe; Liu, Qiao; Zhang, Xiyu; Liu, Jinsong; Wei, Jian‐Jun; Gong, Yaoqin; Liu, Zhaojian; Shao, Changshun

doi:10.1038/cddis.2017.471

Cited by 73 publications

(42 citation statements)

References 28 publications

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“…In addition, berberine modulated the sensitivity of cisplatin through the miR-93/PTEN/AKT signaling pathway in ovarian cancer cells (32) and attenuated the antitumor activity of 5-FU, camptothecin and paclitaxel (33). Berberine was also found to sensitize cancer cells to PARP and epidermal growth factor receptor inhibitors (18,34). In the present study, berberine and sorafenib were found to exert anti-proliferative effects on HCC cells in a dose-and time-dependent manner.…”

Section: Discussionsupporting

confidence: 52%

Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib

Huang

Wang

et al. 2018

Oncol Rep

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Sorafenib resistance is one of the major factors affecting the prognosis of patients with hepatocellular carcinoma (HCC). Increasing evidence has indicated that certain traditional medicines can enhance the sensitivity of cancer cells to sorafenib. Berberine, an isoquinoline alkaloid, has been demonstrated to possess antitumor properties against various malignancies. However, the synergistic effect of the combination of berberine and sorafenib in HCC remains unknown. The aim of the present study was to determine the effects of berberine and sorafenib combination on the growth of liver cancer cells. Initially, it was observed that the combination of sorafenib and berberine exerted a synergistic inhibitory effect on the proliferation of SMMC‑7721 and HepG2 cells in a dose‑ and time‑dependent manner by an MTS assay. Edu staining and colony formation assays also revealed that the combination of 100 µM berberine and 4 µM sorafenib exhibited a significant anti‑proliferation effect on SMMC‑7721 and HepG2 cells. Furthermore, western blotting assay indicated that the expressions levels of cleaved poly(ADP‑ribose) polymerase and cleaved caspase‑3 increased, while those of the anti‑apoptotic protein B‑cell lymphoma 2 and vascular endothelial growth factor decreased. To the best of our knowledge, this is the first study to demonstrate that berberine sensitized liver cancer cells to sorafenib treatment. These results suggest that berberine combined with sorafenib is able to inhibit the proliferation of liver cancer cells and induce apoptosis, which provides evidence for further clinical investigation in HCC patients with sorafenib resistance.

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Section: Discussionsupporting

confidence: 52%

Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib

Huang

Wang

et al. 2018

Oncol Rep

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“…(Berberidaceae) has long been a part of traditional Chinese and Ayurvedic medicine. Preclinical efficacy of berberine has been established in various cancers including colon , breast (Zhao et al, 2017), gastrointestinal (Hesari et al, 2018), oral , liver (Tsang et al, 2015), pancreas (Abrams et al, 2019), prostate (Youn et al, 2018), ovarian (Hou et al, 2017), and cervical (Mahata et al, 2011) cancers. Despite large preclinical efficacy data, clinical trials related to the evaluation of true potential of berberine as an anticancer agent are limited.…”

Section: Phytochemicals Evaluated In Clinical Trialsmentioning

confidence: 99%

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

et al. 2020

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Cancer is a severe health problem that continues to be a leading cause of death worldwide. Increasing knowledge of the molecular mechanisms underlying cancer progression has led to the development of a vast number of anticancer drugs. However, the use of chemically synthesized drugs has not significantly improved the overall survival rate over the past few decades. As a result, new strategies and novel chemoprevention agents are needed to complement current cancer therapies to improve efficiency. Naturally occurring compounds from plants known as phytochemicals, serve as vital resources for novel drugs and are also sources for cancer therapy. Some typical examples include taxol analogs, vinca alkaloids such as vincristine, vinblastine, and podophyllotoxin analogs. These phytochemicals often act via regulating molecular pathways which are implicated in growth and progression of cancer. The specific mechanisms include increasing antioxidant status, carcinogen inactivation, inhibiting proliferation, induction of cell cycle arrest and apoptosis; and regulation of the immune system. The primary objective of this review is to describe what we know to date of the active compounds in the natural products, along with their pharmacologic action and molecular or specific targets. Recent trends and gaps in phytochemical based anticancer drug discovery are also explored. The authors wish to expand the phytochemical research area not only for their scientific soundness but also for their potential druggability. Hence, the emphasis is given to information about anticancer phytochemicals which are evaluated at preclinical and clinical level.

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“…Studies have demonstrated that cellular senescence is a natural barrier in the development of human cancer . Induction of senescent‐like growth arrest has become a new strategy for anticancer treatment . Thus, these results have important implications for matrine in the treatment of GBM, particularly due to the fact that aberrant signaling of PI3K/AKT occurs in GBM through the frequent loss of the tumor suppressor gene PTEN .…”

Section: Discussionmentioning

confidence: 99%

Matrine induces senescence of human glioblastoma cells through suppression of the IGF1/PI3K/AKT/p27 signaling pathway

Zhou

Wang

et al. 2018

Cancer Medicine

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BackgroundMatrine, a traditional Chinese medicine, has recently been shown to have antitumor properties in diverse cancer cells. Here, we explored the effect of matrine on human glioblastoma multiforme (GBM) cells.MethodsGlioblastoma multiforme cell lines were treated with matrine to assess proliferation and viability using EdU and CCK8 assays. SA‐β‐gal assays were used to evaluate cellular senescence, and a cytokine array and ELISA assay were used to screen for secreted cytokines altered in GBM cells after matrine treatment. Immunohistochemistry and Western blot analysis were performed to evaluate protein levels in matrine‐treated cell lines and in samples obtained from orthotopic xenografts. Specific activators of AKT and IGF1 were used to identify the pathways mediating the effect.ResultsMatrine potently inhibited growth of GBM cell lines in vitro. Based on in situ assays, growth arrest induced by matrine was primarily achieved through induction of cellular senescence. Matrine treatment led to decreased expression of proteins involved in promoting cell growth, IGF1, PI3K, and pAKT. Exposure of cells to a small molecule activating AKT (SC79) and recombinant IGF1 led to a reduced number of senescent SA‐β‐gal‐positive cells in the presence of matrine. Finally, matrine inhibited growth of orthotopic xenografts established from luciferase‐stable‐U251 or luciferase‐stable‐P3 cells and prolonged overall survival in mice.ConclusionsThese results indicated that matrine arrested cell growth through inhibition of IGF1/PI3K/AKT signaling. Matrine warrants further investigation as a potential therapy in the treatment of patients with GBM.

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Berberine induces oxidative DNA damage and impairs homologous recombination repair in ovarian cancer cells to confer increased sensitivity to PARP inhibition

Cited by 73 publications

References 28 publications

Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib

Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

Matrine induces senescence of human glioblastoma cells through suppression of the IGF1/PI3K/AKT/p27 signaling pathway

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