Berberine, a natural alkaloid sensitizes human hepatocarcinoma to ionizing radiation by blocking autophagy and cell cycle arrest resulting in senescence

Ramesh, Gautham; Das, Shubhankar; Sadashiva, Satish Rao Bola

doi:10.1111/jphp.13354

Cited by 12 publications

(9 citation statements)

References 68 publications

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“…et al, 2019 ). In addition, berberine can sensitize human HCC cells to ionizing radiation therapy by blocking autophagy at LC3-II manner and inducing G 2 /M phase arrest via the upregulation of mitochondrial oxidative stress and the inhibition of ATP levels, resulting in senescence ( Ramesh et al, 2020 ). Additionally, berberine induces DNA repair by affecting DNA repair protein XRCC1-mediated base excision repair to enhance the sensitization of breast cancer cells to cisplatin, camptothecin, and methyl methanesulfonate ( Gao et al, 2019 ).…”

Section: Combination Therapymentioning

confidence: 99%

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Chen

Liang

et al. 2022

Front. Pharmacol.

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Cancer is a serious disease with an increasing number of reported cases and high mortality worldwide. Gastrointestinal cancer defines a group of cancers in the digestive system, e.g., liver cancer, colorectal cancer, and gastric cancer. Coptidis Rhizoma (C. Rhizoma; Huanglian, in Chinese) is a classical Chinese medicinal botanical drug for the treatment of gastrointestinal disorders and has been shown to have a wide variety of pharmacological activity, including antifungal, antivirus, anticancer, antidiabetic, hypoglycemic, and cardioprotective effects. Recent studies on C. Rhizoma present significant progress on its anticancer effects and the corresponding mechanisms as well as its clinical applications. Herein, keywords related to C. Rhizoma, cancer, gastrointestinal cancer, and omics were searched in PubMed and the Web of Science databases, and more than three hundred recent publications were reviewed and discussed. C. Rhizoma extract along with its main components, berberine, palmatine, coptisine, magnoflorine, jatrorrhizine, epiberberine, oxyepiberberine, oxyberberine, dihydroberberine, columbamine, limonin, and derivatives, are reviewed. We describe novel and classic anticancer mechanisms from various perspectives of pharmacology, pharmaceutical chemistry, and pharmaceutics. Researchers have transformed the chemical structures and drug delivery systems of these components to obtain better efficacy and bioavailability of C. Rhizoma. Furthermore, C. Rhizoma in combination with other drugs and their clinical application are also summarized. Taken together, C. Rhizoma has broad prospects as a potential adjuvant candidate against cancers, making it reasonable to conduct additional preclinical studies and clinical trials in gastrointestinal cancer in the future.

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Section: Combination Therapymentioning

confidence: 99%

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Chen

Liang

et al. 2022

Front. Pharmacol.

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“…124 BBR, obtained from Coptidis Rhizoma , triggered autophagic cell death via suppression of the PI3K/Akt/mTOR mechanism and elevation of ROS-mediated mitochondrial dysfunction in HCC Hep3B cells. 125 In addition, BBR sensitized human HCC to ionizing radiation by obstructing cell cycle arrest and autophagy, resulting in senescence, 126 triggered autophagic and apoptotic death in HepG2 cells through the activation of AMPK mechanism, 127 and activated cell death in human hepatoma carcinoma cell line HepG2 through inhibiting the expression of CD147. 128 Finally, BBR suppressed the viability, migration, and invasion capacity of HepG2 cells via the activation of pyroptosis (caspase-1 dependent programmed cell death) both in vitro and in vivo, which was impaired by caspase-1 inhibitor Ac-YVAD-CMK.…”

Section: Mechanistic Effects Of Bbr On Liver Cancermentioning

confidence: 99%

Effects of Berberine on Liver Cancer

Liu

Nwafor

Wang

et al. 2022

Natural Product Communications

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Liver cancer, otherwise known as hepatocellular carcinoma, is a chronic disease condition with an excessive deposition and growth of malignant cells in the body. The high incidence and prevalence rates of liver cancer continue to be problems, as well as its poor prognosis and therapeutic limitations involving severe drug adverse reactions linked to the use of synthetic chemotherapeutic compounds. Continuous experimental studies, as well as utilization of pure herbal-based compounds, are essential towards finding more potent cures for liver cancer. Natural bioactive compounds, particularly alkaloids (eg, berberine), have been shown to be highly beneficial in the treatment of various diseases. Berberine (BBR), an isoquinoline alkaloid, is obtained from stem, bark, roots, rhizomes, and leaves of several medicinal plants, including Berberis species. It is commonly synthesized from the benzyltetrahydroisoquinoline system with the incorporation of an additional carbon atom as a bridge. The multiple attributes of BBR involving effective inhibitory and cytotoxic actions against the proliferation of cancer cells have been demonstrated. The use of BBR in experimental studies (in vivo and in vitro) for over a decade for liver cancer treatment has proven to be highly effective, safe, and potent. Until now, the poor solubility of BBR remains one of the contributing factors leading to its minimal clinical bioavailability. Therefore, BBR could serve as a prospective drug candidate in the future towards drug formulation for liver cancer treatment. The relevant information regarding this review was obtained electronically through the use of databases such as PubMed, Google Scholar, Springer, Hindawi, Embase, Web of Science, and China National Knowledge Infrastructure. All the aforementioned databases were searched from 1981 to 2020. This literature represents an update of previous review papers discussing the various positive pharmacological and mechanistic effects (oxidative stress regulation, inflammation reduction, apoptosis activation, overcoming drug resistance, and metastasis inhibition) of BBR for liver cancer treatment, which would be of great significance to drug development and clinical research.

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“…In addition, BBR has been shown to induce autophagic cell death by increasing the binding capacity of GRP78 levels in cancer cells [ 160 , 161 ]. BBR sensitizes human HCC to ionizing radiation by blocking autophagy and cell-cycle arrest, which results in senescence [ 260 ].…”

Section: Natural Products As Inducers Of Autophagy In Cancermentioning

confidence: 99%

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer

Al-Bari

Ito

Ahmed

et al. 2021

IJMS

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Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic interventions in various diseases, including cancers. According to the framework of autophagy, the suppression or induction of autophagy can exert therapeutic properties through the promotion of cell death or cell survival, which are the two main events targeted by cancer therapies. Remarkably, natural products have attracted attention in the anticancer drug discovery field, because they are biologically friendly and have potential therapeutic effects. In this review, we summarize the up-to-date knowledge regarding natural products that can modulate autophagy in various cancers. These findings will provide a new position to exploit more natural compounds as potential novel anticancer drugs and will lead to a better understanding of molecular pathways by targeting the various autophagy stages of upcoming cancer therapeutics.

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Berberine, a natural alkaloid sensitizes human hepatocarcinoma to ionizing radiation by blocking autophagy and cell cycle arrest resulting in senescence

Cited by 12 publications

References 68 publications

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Effects of Berberine on Liver Cancer

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer

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