Targeting Autophagy with Natural Compounds in Cancer: A Renewed Perspective from Molecular Mechanisms to Targeted Therapy

Xie, Qiang; Chen, Yi; Tan, Huidan; Liu, Bo; Zheng, Lingli; Mu, Yandong

doi:10.3389/fphar.2021.748149

Cited by 21 publications

(12 citation statements)

References 94 publications

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“…It is known that serine/threonine protein kinases—AMP-activated protein kinase, mammalian target of rapamycin (mTOR) and unc-51-like kinase 1/2 (Ulk1/2)—are three closely connected junctions in the signaling network that regulates autophagy [ 48 ]. The perspectives and influences of natural compounds on autophagy in cancer were renewed [ 49 ]. The effect of our extracts (DE, SWE) on the level of autophagy in malignant cell lines (breast and cervical) was assessed by the Western blot analysis of the ULK1 protein.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Resveratrol-Rich Extracts of Vitis vinifera Pruning Waste on HeLa, MCF-7 and MRC-5 Cells: Apoptosis, Autophagia and Necrosis Interplay

et al. 2022

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Resveratrol is a well-studied plant-derived molecule in cancer biology, with a plethora of documented in vitro effects. However, its low bioavailability and toxicity risk hamper its wider use. In this study, vine shoots after pruning were used as a source of resveratrol (RSV). The activity of subcritical water extract (SWE) and dry extract (DE) is examined on three cell lines: HeLa, MCF-7 and MRC-5. The cytotoxic effect is assessed by the MTT test and EB/AO staining, levels of apoptosis are determined by Annexin V assay, autophagia by ULK-1 expression using Western blot and NF-kB activation by p65 ELISA. Our results show that both resveratrol-rich extracts (DE, SWE) have a preferential cytotoxic effect on malignant cell lines (HeLa, MCF-7), and low cytotoxicity on non-malignant cells in culture (MRC-5). Further experiments indicate that the investigated malignant cells undergo different cell death pathways. MCF-7 cells died preferentially by apoptosis, while the HeLa cells died most likely by necrosis (possibly ferroptosis). Protective autophagia is diminished upon treatment with DE in both HeLa and MCF-7 cells, while SWE does not influence the level of autophagia. The extracts are effective even at low concentrations (below IC50) in the activation of NF-kB (p65 translocation).

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Section: Discussionmentioning

confidence: 99%

The Effects of Resveratrol-Rich Extracts of Vitis vinifera Pruning Waste on HeLa, MCF-7 and MRC-5 Cells: Apoptosis, Autophagia and Necrosis Interplay

et al. 2022

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“…Hence, developing relevant drugs targeting autophagy will be a promising strategy for treating diseases that are unavailable with conventional medicinal treatment. Indeed, remarkable progress has been made in discovering small molecules targeting autophagy, such as chloroquine and hydroxychloroquine, in recent years ( Limpert et al, 2018 ; Xiang et al, 2020 ; Xie et al, 2021 ). However, current achievements gradually fail to fulfill the vast and complex drug needs in the clinic.…”

Section: Introductionmentioning

confidence: 99%

Recent advances of tanshinone in regulating autophagy for medicinal research

Zhao

Wang

et al. 2023

Front. Pharmacol.

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Initially described as an ancient and highly conserved catabolic biofunction, autophagy plays a significant role in disease pathogenesis and progression. As the bioactive ingredient of Salvia miltiorrhiza, tanshinone has recently shown profound effects in alleviating and treating various diseases by regulating autophagy. However, compared to the remarkable achievements in the known pharmacological effects of this traditional Chinese medicine, there is a lack of a concise and comprehensive review deciphering the mechanism by which tanshinone regulates autophagy for medicinal research. In this context, we concisely review the advances of tanshinone in regulating autophagy for medicinal research, including human cancer, the nervous system, and cardiovascular diseases. The pharmacological effects of tanshinone targeting autophagy involve the regulation of autophagy-related proteins, such as Beclin-1, LC3-II, P62, ULK1, Bax, ATG3, ATG5, ATG7, ATG9, and ATG12; the regulation of the PI3K/Akt/mTOR, MEK/ERK/mTOR, Beclin-1-related, and AMPK-related signaling pathways; the accumulation of reactive oxygen species (ROS); and the activation of AMPK. Notably, we found that tanshinone played a dual role in human cancers in an autophagic manner, which may provide a new avenue for potential clinical application. In brief, these findings on autophagic tanshinone and its derivatives provide a new clue for expediting medicinal research related to tanshinone compounds and autophagy.

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“…Clinical management of patients diagnosed with NSCLC initially depends on the diagnosed stage and is subsequently treated using surgical resection, followed by chemo-and/or radiotherapeutics [2]. Nevertheless, although the past few years have witnessed advances in the therapeutic approaches of lung cancer, the overall five-year survival rate is still only 19% [3]. Such poor prognosis in lung cancer patients has been attributed mainly to the development of resistance towards antineoplastic agents [4].…”

Section: Introductionmentioning

confidence: 99%

Screening of Apoptosis Pathway-Mediated Anti-Proliferative Activity of the Phytochemical Compound Furanodienone against Human Non-Small Lung Cancer A-549 Cells

Saqr

Khafagy

Aldawsari

et al. 2022

Life

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Furanodienone (FDN), a major bioactive component of sesquiterpenes produced from Rhizoma curcumae, has been repeatedly acknowledged for its intrinsic anticancer efficacy against different types of cancer. In this study, we aimed to investigate the cytotoxic potential of furanodienone against human lung cancer (NSCLC A549) cells in vitro, as well as its underlying molecular mechanisms in the induction of apoptosis. Herein, we found that FDN significantly inhibited the proliferation of A549 cells in a dose-dependent manner. In addition, treatment with FDN potentially triggered apoptosis in A549 cells via not only disrupting the nuclear morphology, but by activating capsase-9 and caspase-3 with concomitant modulation of the pro- and antiapoptotic gene expression as well. Furthermore, FDN revealed its competence in inducing cell cycle arrest at G0/G1 phase in A549 cells, which was associated with decreased expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4), along with increased expression of CDK inhibitor p21Cip1. Intriguingly, FDN treatment efficiently downregulated the Wnt signaling pathway, which was correlated with increased apoptosis, as well as cell cycle arrest, in A549 cells. Collectively, FDN might represent a promising adjuvant therapy for the management of lung cancer.

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Targeting Autophagy with Natural Compounds in Cancer: A Renewed Perspective from Molecular Mechanisms to Targeted Therapy

Cited by 21 publications

References 94 publications

The Effects of Resveratrol-Rich Extracts of Vitis vinifera Pruning Waste on HeLa, MCF-7 and MRC-5 Cells: Apoptosis, Autophagia and Necrosis Interplay

The Effects of Resveratrol-Rich Extracts of Vitis vinifera Pruning Waste on HeLa, MCF-7 and MRC-5 Cells: Apoptosis, Autophagia and Necrosis Interplay

Recent advances of tanshinone in regulating autophagy for medicinal research

Screening of Apoptosis Pathway-Mediated Anti-Proliferative Activity of the Phytochemical Compound Furanodienone against Human Non-Small Lung Cancer A-549 Cells

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