Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

Pang, Xuening; Zhang, Xiaoyi; Jiang, Yulin; Su, Quanzhong; Li, Qun; Li, Zichao

doi:10.3390/biom11020135

Cited by 56 publications

(36 citation statements)

References 163 publications

(247 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Galangin is a flavonol that can inhibit HepG2 cells proliferation via the induction of autophagy, through activating the transforming growth factor (TGF)‐beta receptor/Smad pathway and augmented the expression of some ATGs (autophagy‐related gene proteins) reducing cell proliferation and inducing cell apoptosis (Wang et al., 2014). Galangin was found to have the ability to induce autophagy through activation of a P53 signaling pathway in HepG2 cells (Pang et al, 2021; Wen et al., 2012). Baicalein overcomes multi‐drug resistance (MDR) via autophagy and apoptosis in MDR HCC cells, Bel7402/5‐FU by downregulating the expression of P‐gp and Bcl‐xl (Li et al., 2018, Pang et al, 2021).…”

Section: Molecular Mechanism Of the Anticancer Effect Of Flavonoidmentioning

confidence: 99%

“…Galangin was found to have the ability to induce autophagy through activation of a P53 signaling pathway in HepG2 cells (Pang et al, 2021; Wen et al., 2012). Baicalein overcomes multi‐drug resistance (MDR) via autophagy and apoptosis in MDR HCC cells, Bel7402/5‐FU by downregulating the expression of P‐gp and Bcl‐xl (Li et al., 2018, Pang et al, 2021). Resveratrol is found to induce anti‐tumor activity by modulating the autophagy signaling pathway.…”

Section: Molecular Mechanism Of the Anticancer Effect Of Flavonoidmentioning

confidence: 99%

“…Quercetin‐induced autophagy by inhibiting the activation of the MAPK signaling pathway and Akt/mTOR pathway. Both in vitro and in vivo studies indicate the apoptotic cell death induced by autophagic stimulation (Ji et al., 2019; Pang et al, 2021).…”

Section: Molecular Mechanism Of the Anticancer Effect Of Flavonoidmentioning

confidence: 99%

See 2 more Smart Citations

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

et al. 2021

View full text Add to dashboard Cite

Chemopreventive approaches with food‐derived phytochemicals are progressively rising as a significant aspect of tumor management and control. Herein, we have showcased the major phytoconstituents belonging to the group of flavanoid, as anti‐cancer agents used for the treatment and prevention of hepatocellular carcinoma (HCC). Sorafenib is the sole drug used for the treatment of advanced HCC, but its clinical application is limited because of its severe adverse effects and drug resistance. Diet‐based chemoprevention seems to be the way forward for this disease of malignant nature. As HCC is derived from a chronic inflammatory milieu, the regular incorporation of bioactive phytochemicals in the diet will confer protection and prevent progression to hepatocarcinogenesis. Many preclinical studies proved that the health benefits of flavonoids confer cytotoxic potential against various types of cancers including hepatocellular carcinoma. As flavonoids with excellent safety profile are abundantly present in common vegetables and fruits, they can be better utilized for chemoprevention and chemosensitization in such chronic condition. This review highlights the plausible role of the eight most promising flavonoids (Curcumin, Kaempferol, Resveratrol, Quercetin, Silibinin, Baicalein, Galangin and Luteolin) as key orchestrators of chemoprevention in hepatocellular carcinoma with preclinical and clinical evidence. An attempt to address the challenges in its clinical translation is also included. This review also provides an insight into the close association of HCC and metabolic disorders which may further decipher the chemopreventive effect of dietary bioactive from a proof of concept to extensive clinical translation. Practical applications According to GLOBOCAN 2020 database, it is estimated that 905,677 new cases of liver cancer and approximately 830,180 deaths related to that. The cancer incidence and mortality are almost similar as it is diagnosed at an advanced stage in patients where systemic drug therapy is the sole approach. Due to the emergence of multidrug resistance and drug‐related toxicities, most of the patient can not adhere to the therapy regimen. Flavonoids are known to be a potential anticancer agent with an excellent safety profile. These are found to be effective preclinically against hepatocellular carcinoma through modulation of numerous pathways in hepatocarcinogenesis. But, the bioavailability issue, lack of well designed‐validated clinical evidence, the possibility of food–drug interaction etc limit its clinical utility. The research inputs mainly to overcome pharmacokinetic issues along with suitable validation of efficacy and toxicity will be a critical point for establishing flavonoids as an effective, safe, affordable therapeutics.

show abstract

Section: Molecular Mechanism Of the Anticancer Effect Of Flavonoidmentioning

confidence: 99%

Section: Molecular Mechanism Of the Anticancer Effect Of Flavonoidmentioning

confidence: 99%

See 1 more Smart Citation

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Cancer cell death is often caused by apoptosis, which is considered to be the principal anticancer mechanism ( 16 ). However, it has been documented that autophagy and apoptosis are intertwined processes ( 17 ). Autophagy is the process of engulfing and degrading cytosolic proteins and damaged organelles ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Chrysin induces autophagy through the inactivation of the ROS‑mediated Akt/mTOR signaling pathway in endometrial cancer

Shi

Yang

et al. 2021

Int J Mol Med

View full text Add to dashboard Cite

Endometrial cancer (EC) is widely known as an aggressive malignancy. Due to the limited therapeutic options and poor prognosis of patients with advanced-stage EC, there is a need to identify effective alternative treatments. Chrysin is a naturally active flavonoid (5,7-dihydroxyflavone), which has been demonstrated to exert anticancer effects and may present a novel strategy for EC treatment. However, the role of chrysin in EC remains largely unclear. The aim of the present study was to examine the anticancer effects of chrysin on EC. The results revealed that, in addition to apoptosis, chrysin increased the LC3II expression levels and markedly accelerated the autophagic flux, suggesting that chrysin induced both the autophagy and apoptosis of EC cells. Furthermore, the inhibition of autophagy by chloroquine enhanced the inhibitory effect on cell proliferation and the promotion of the chrysin-induced apoptosis of EC cells, indicating that chrysin-induced autophagy was a cytoprotective mechanism. Additionally, chrysin led to the production of intracellular reactive oxygen species (ROS). N-acetylcysteine (NAC) pretreatment significantly inhibited chrysin-induced autophagy, suggesting that ROS activated autophagy induced by chrysin in EC cells. Furthermore, the phosphorylated (p-) Akt and p-mTOR levels were significantly decreased in a concentration-dependent manner following treatment with chrysin, while NAC blocked these effects. Taken together, these findings demonstrated that chrysin-induced autophagy via the inactivation of the ROS-mediated Akt/mTOR signaling pathway in EC cells.

show abstract

“…Macroautophagy is a metabolic process in which cells wrap proteins or organelles to form autophagosomes through bilayer membranes. Then, the outer membrane fuses with the lysosomal membrane to form autolysosomes and finally degrades the wrapped contents by hydrolyzing enzymes [ 20 ]. The process of autophagy begins with the formation of autophagosomes, which includes initiation, nucleation, prolongation, and closure.…”

Section: Autophagymentioning

confidence: 99%

Autophagy in Gastric Mucosa: The Dual Role and Potential Therapeutic Target

Guo

Chai

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

The incidence of stomach diseases is very high, which has a significant impact on human health. Damaged gastric mucosa is more vulnerable to injury, leading to bleeding and perforation, which eventually aggravates the primary disease. Therefore, the protection of gastric mucosa is crucial. However, existing drugs that protect gastric mucosa can cause nonnegligible side effects, such as hepatic inflammation, nephritis, hypoacidity, impotence, osteoporotic bone fracture, and hypergastrinemia. Autophagy, as a major intracellular lysosome-dependent degradation process, plays a key role in maintaining intracellular homeostasis and resisting environmental pressure, which may be a potential therapeutic target for protecting gastric mucosa. Recent studies have demonstrated that autophagy played a dual role when gastric mucosa exposed to biological and chemical factors. More indepth studies are needed on the protective effect of autophagy in gastric mucosa. In this review, we focus on the mechanisms and the dual role of various biological and chemical factors regulating autophagy, such as Helicobacter pylori, virus, and nonsteroidal anti-inflammatory drugs. And we summarize the pathophysiological properties and pharmacological strategies for the protection of gastric mucosa through autophagy.

show abstract

Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

Cited by 56 publications

References 163 publications

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

Chrysin induces autophagy through the inactivation of the ROS‑mediated Akt/mTOR signaling pathway in endometrial cancer

Autophagy in Gastric Mucosa: The Dual Role and Potential Therapeutic Target

Contact Info

Product

Resources

About