The anti‐tumourigenic effect of ellagic acid in SKOV‐3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK

Elsaid, Fahmy G.; Al-Shehri, Mohamed A.; Shati, Ali A.; Alkahtani, Mohammed Ali; Alsheri, A. S.; Massoud, Ehab El Sayed; El‐kott, Attalla F.; El-Mekkawy, Haitham; Al‐Ramlawy, Amira M.; Abdraboh, Mohamed E.

doi:10.1111/1440-1681.13338

Cited by 11 publications

(9 citation statements)

References 28 publications

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“…Duan et al reported that ellagic acid (10-50 µM) activated autophagy, but not apoptosis, in lung cancer cells (HOP62 and H1975), and in tumor-bearing mice (40 mg/kg, i.p., every 2 days, for 22 days), as demonstrated by the formation of LC3-positive autophagosomes, the increase in LC3 II, ATG5 and the reduced levels of p62 [238]. Similarly, ellagic acid (36.6 µM) inhibited cell growth and the invasiveness of ovarian cancer SKOV-3 cells and stimulated apoptosis by activating cytotoxic autophagy, as indicated by the increase in the levels of Beclin 1, ATG5, LC3I/II and decrease in p62 [239]. In addition, it was shown that ellagic acid activated autophagy through the downregulation of mTORC1 and Akt, and the activation of AMPK [238,239].…”

Section: Phenolic Acidsmentioning

confidence: 97%

“…Similarly, ellagic acid (36.6 µM) inhibited cell growth and the invasiveness of ovarian cancer SKOV-3 cells and stimulated apoptosis by activating cytotoxic autophagy, as indicated by the increase in the levels of Beclin 1, ATG5, LC3I/II and decrease in p62 [239]. In addition, it was shown that ellagic acid activated autophagy through the downregulation of mTORC1 and Akt, and the activation of AMPK [238,239]. The activation of apoptotic and autophagic cell death was also reported for punicalagin, an ellagitannin isolated from the fruit of Punica granatum L. trees.…”

Section: Phenolic Acidsmentioning

confidence: 99%

See 1 more Smart Citation

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Benvenuto

Albonici

Focaccetti

et al. 2020

IJMS

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One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants.

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Section: Phenolic Acidsmentioning

confidence: 97%

Section: Phenolic Acidsmentioning

confidence: 99%

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Benvenuto

Albonici

Focaccetti

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…The antitumorigenic potential of ellagic acid confirmed in SKOV-3 OC cells involved cytotoxic autophagy activation mediated by Akt inhibition and AMPK activation. Mechanistically, it decreased the levels of the two downstream targets, mTORC1 and p-Akt, but increased the levels of AMPK (Thr172) [ 78 ]. PI3K/Akt inhibits autophagy by activating mTORC1, and AMPK inhibits mTORC1, thus activating autophagy.…”

Section: Phenolic Acids Involved In the Regulation Of Molecular Targetsmentioning

confidence: 99%

“…EA also inhibits angiogenesis by inhibiting growth factor VEGF secretion [ 43 ]. Ellagic acid-induced apoptotic induction (caspase-3 mediated via an increased Bax: Bcl-2 ratio and JNK and Akt phosphorylation) and cytotoxic autophagy activation (Akt inhibition and AMPK activation) enhances the efficacy of EA-based chemotherapy [ 74 , 78 ]. Thus, the key role in cellular apoptosis and dysregulated autophagy in ovarian cancer development and progression indicates its potential as a promising therapeutic target.…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Phenolic Acids-Mediated Regulation of Molecular Targets in Ovarian Cancer: Current Understanding and Future Perspectives

et al. 2023

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Cancer is a global health concern with a dynamic rise in occurrence and one of the leading causes of mortality worldwide. Among different types of cancer, ovarian cancer (OC) is the seventh most diagnosed malignant tumor, while among the gynecological malignancies, it ranks third after cervical and uterine cancer and sadly bears the highest mortality and worst prognosis. First-line treatments have included a variety of cytotoxic and synthetic chemotherapeutic medicines, but they have not been particularly effective in extending OC patients’ lives and are associated with side effects, recurrence risk, and drug resistance. Hence, a shift from synthetic to phytochemical-based agents is gaining popularity, and researchers are looking into alternative, cost-effective, and safer chemotherapeutic strategies. Lately, studies on the effectiveness of phenolic acids in ovarian cancer have sparked the scientific community’s interest because of their high bioavailability, safety profile, lesser side effects, and cost-effectiveness. Yet this is a road less explored and critically analyzed and lacks the credibility of the novel findings. Phenolic acids are a significant class of phytochemicals usually considered in the nonflavonoid category. The current review focused on the anticancer potential of phenolic acids with a special emphasis on chemoprevention and treatment of OC. We tried to summarize results from experimental, epidemiological, and clinical studies unraveling the benefits of various phenolic acids (hydroxybenzoic acid and hydroxycinnamic acid) in chemoprevention and as anticancer agents of clinical significance.

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“…The p21 and p53 levels undergo upregulation by ellagic acid to induce apoptosis in prostate cancer cells [ 207 ]. The ellagic acid stimulates autophagy via Akt down-regulation and AMPK upregulation to reduce viability and survival of ovarian cancer cells [ 208 ]. The ellagic acid is a potent agent in suppressing drug resistance via down-regulating P-glycoprotein (P-gp_levels [ 209 ].…”

Section: Dietary Agents and Cancer Stem Cellsmentioning

confidence: 99%

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

Paskeh

Asadi²,

Zabolian

et al. 2021

IJMS

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As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/β-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.

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The anti‐tumourigenic effect of ellagic acid in SKOV‐3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK

Cited by 11 publications

References 28 publications

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Phenolic Acids-Mediated Regulation of Molecular Targets in Ovarian Cancer: Current Understanding and Future Perspectives

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

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