Lower dose of metformin combined with artesunate induced autophagy-dependent apoptosis of glioblastoma by activating ROS-AMPK-mTOR axis

Ding, Wencong; Liao, Lingxiao; Liu, Jia; Zhao, Jiaxing; Tang, Qiong-Yan; Liao, Yongshi

doi:10.1016/j.yexcr.2023.113691

Cited by 7 publications

(2 citation statements)

References 33 publications

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“…It has been discovered that both the metformin and artesunate have antitumor activity in recent years. Latest research has shown that artesunate in combination with metformin can be used to treat glioblastoma multiforme, which requires 75 μM of artesunate and 20 mM of metformin [ 25 ]. However, metformin has significant cytotoxicity at high doses (20 mM to 50 mM), which means that the combination regimen is still not suitable for clinical treatment [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Novel artesunate-metformin conjugate inhibits bladder cancer cell growth associated with Clusterin/SREBP1/FASN signaling pathway

Lin,

Yang,

Wang

et al. 2024

Korean J Physiol Pharmacol

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Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Novel artesunate-metformin conjugate inhibits bladder cancer cell growth associated with Clusterin/SREBP1/FASN signaling pathway

Lin,

Yang,

Wang

et al. 2024

Korean J Physiol Pharmacol

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“…In addition, intervention with AS has been shown to reverse increased retinal thickness in diabetic rats, with the activation of the AMPK/SIRT1 pathway promoting retinal autophagy by upregulating Beclin-1 and LC3II/I levels and downregulating p62 levels [ 105 ]. In vitro experiments demonstrated that AS, in combination with metformin, triggers autophagy-dependent cell death in glioblastoma by disrupting the ROS-AMPK-mTOR axis [ 106 ]. Kong et al emphasized the upregulation of LC3 levels and the downregulation of Atg3/5, Atg6/Beclin1, Atg12, p62, FTH1, and nuclear receptor co-activator 4 (NCOA4) mRNA levels, which are involved in the anti-hepatocellular fibrosis effects of AS [ 83 ].…”

Section: Protective Effects and Action Mechanisms Of Asmentioning

confidence: 99%

Artesunate Exerts Organ- and Tissue-Protective Effects by Regulating Oxidative Stress, Inflammation, Autophagy, Apoptosis, and Fibrosis: A Review of Evidence and Mechanisms

Zhu,

Wang,

Han

et al. 2024

Antioxidants

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The human body comprises numerous organs and tissues operating in synchrony, it facilitates metabolism, circulation, and overall organismal function. Consequently, the well-being of our organs and tissues significantly influences our overall health. In recent years, research on the protective effects of artesunate (AS) on various organ functions, including the heart, liver, brain, lungs, kidneys, gastrointestinal tract, bones, and others has witnessed significant advancements. Findings from in vivo and in vitro studies suggest that AS may emerge as a newfound guardian against organ damage. Its protective mechanisms primarily entail the inhibition of inflammatory factors and affect anti-fibrotic, anti-aging, immune-enhancing, modulation of stem cells, apoptosis, metabolic homeostasis, and autophagy properties. Moreover, AS is attracting a high level of interest because of its obvious antioxidant activities, including the activation of Nrf2 and HO-1 signaling pathways, inhibiting the release of reactive oxygen species, and interfering with the expression of genes and proteins associated with oxidative stress. This review comprehensively outlines the recent strides made by AS in alleviating organismal injuries stemming from various causes and protecting organs, aiming to serve as a reference for further in-depth research and utilization of AS.

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Dual perspective on autophagy in glioma: Detangling the dichotomous mechanisms of signaling pathways for therapeutic insights

Kundu,

Das,

Dey

et al. 2024

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Lower dose of metformin combined with artesunate induced autophagy-dependent apoptosis of glioblastoma by activating ROS-AMPK-mTOR axis

Cited by 7 publications

References 33 publications

Novel artesunate-metformin conjugate inhibits bladder cancer cell growth associated with Clusterin/SREBP1/FASN signaling pathway

Novel artesunate-metformin conjugate inhibits bladder cancer cell growth associated with Clusterin/SREBP1/FASN signaling pathway

Artesunate Exerts Organ- and Tissue-Protective Effects by Regulating Oxidative Stress, Inflammation, Autophagy, Apoptosis, and Fibrosis: A Review of Evidence and Mechanisms

Dual perspective on autophagy in glioma: Detangling the dichotomous mechanisms of signaling pathways for therapeutic insights

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