Berberine activates caspase-9/cytochrome c-mediated apoptosis to suppress triple-negative breast cancer cells in vitro and in vivo

Zhao, Yuwan; Jing, Zuolei; Lv, Jian; Zhang, Zhiwei; Lin, Jie; Cao, Xuejiao; Zhao, Zinan; Liu, Pixu; Mao, Weifeng

doi:10.1016/j.biopha.2017.08.045

Cited by 103 publications

(62 citation statements)

References 27 publications

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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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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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“…Berberine has extensive pharmacological effects, including anti-hypertensive, anti-diabetic, anti-arrhythmia and anti-hyperlipidemic (3)(4)(5)(6). Recent studies have shown that berberine exerts antitumor effects in a variety of human cancer cells, such as breast cancer, hepatocellular carcinoma, leukemia, and esophageal cancer, both in vitro and in vivo, by suppressing proliferation, inducing apoptosis, arresting the cell cycle, and inhibiting invasion and metastasis (7)(8)(9)(10)(11)(12). In addition, it has been recently reported that berberine-induced autophagy has been observed in hepatic and colon cancer cells (13,14).…”

Section: Introductionmentioning

confidence: 99%

Berberine induces mitochondrial‑mediated apoptosis and protective autophagy in human malignant pleural mesothelioma NCI‑H2452 cells

Yao

Wan

et al. 2018

Oncol Rep

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Increasing evidence shows that berberine has antitumor effects against a number of tumor cells. In the present study, we evaluated the effect of berberine on the proliferation of the human malignant pleural mesothelioma (MPM) cell line NCI-H2452, and explored the therapeutic potential and underlying mechanisms of this agent. Our results showed that berberine inhibited the proliferation of NCI-H2452 cells in a dose-and time-dependent manner and could induce apoptosis, possibly through a caspase-9-dependent intrinsic mitochondrial pathway. In addition, autophagy was induced by berberine, which was characterized by the accumulation of LC3-II and decreased p62 expression. We used inhibitors of apoptosis and autophagy, and an inducer of autophagy, to evaluate the significance of autophagy in berberine-induced cell death. The results demonstrated that apoptosis is the primary route through which berberine induces NCI-H2452 cell death. Berberine-induced autophagy may be an adaptive response to antitumor agents and have a protective role in MPM cells. Inhibition of autophagy enhanced berberine-induced apoptosis. Therefore, inhibition of autophagy may be an effective treatment strategy in the management of MPM. In conclusion, berberine is a potent antitumor agent for treating MPM, and it induces mitochondrial-mediated apoptosis and protective autophagy in human NCI-H2452 MPM cells.

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“…In this paper, berberine showed an interesting inhibitory effect of the proliferation of several TNBC cell lines (BT-20, HCC70, MDA-MB-468, MDA-MB-231, HCC1143, BT-549, HCC38 and HCC1937) with an IC 50 ranging from 0.19 µM to 16.7 µM; with BT-20, HCC70 and MDA-MB-468 being the most sensitive ones and BT-549 and MDA-MB-231 being the most resistant ones to berberine treatment. In fact, recent studies have found that berberine inhibits TNBC cell growth and metastasis [15][16][17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, berberine is also known for its ability to engender apoptosis in several cancer types including breast cancer cells by triggering DNA damage [28]. Moreover, a previous study reported that berberine induces DNA strand breaks in MDA-MB-231 and BT-549 TNBC cell lines at 49.08 µM and 44.58 µM, respectively, in 48h upon the treatment [16]. Some studies suggest that berberine may directly bind to DNA by intercalation [28].…”

Section: Discussionmentioning

confidence: 99%

Berberine Impairs the Survival of Triple Negative Breast Cancer Cells: Cellular and Molecular Analyses

et al. 2020

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Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. Non-available targeted therapy for TNBC represents its biggest treatment challenge. Thus, finding new promising effective drugs is urgently needed. In the present study, we investigated how berberine, a natural isoquinoline, impairs the survival of TNBC cells in both cellular and molecular levels. Our experimental model was based on the use of eight TNBC cell lines: MDA-MB-468, MDA-MB-231, HCC70, HCC38, HCC1937, HCC1143, BT-20, and BT-549. Berberine was cytotoxic against all treated TNBC cell lines. The most sensitive cell lines were HCC70 (IC 50 = 0.19 µM), BT-20 (IC 50 = 0.23 µM) and MDA-MB-468 (IC 50 = 0.48 µM). Using flow cytometry techniques, berberine, at 0.5 and 1 µM for 120 and 144 h, not only induced cell cycle arrest, at G1 and/or G2/M phases, but it also triggered significant apoptosis. At the molecular level, these results are consistent with the expression of their related proteins using Western blot assays. Interestingly, while berberine was cytotoxic against TNBC cells, it had no effect on the viability of normal human breast cells MCF10A cultured in a 3D matrigel model. These results suggest that berberine may be a good potential candidate for TNBC drug development.

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Berberine activates caspase-9/cytochrome c-mediated apoptosis to suppress triple-negative breast cancer cells in vitro and in vivo

Cited by 103 publications

References 27 publications

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

Berberine induces mitochondrial‑mediated apoptosis and protective autophagy in human malignant pleural mesothelioma NCI‑H2452 cells

Berberine Impairs the Survival of Triple Negative Breast Cancer Cells: Cellular and Molecular Analyses

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