Melatonin effect on breast and ovarian cancers by targeting the PI3K/Akt/mTOR pathway.

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY IUBMB Life Pub Date : 2024-08-30 DOI:10.1002/iub.2900
Vahid Pourbarkhordar, Sohrab Rahmani, Ali Roohbakhsh, A Wallace Hayes, Gholamreza Karimi
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Abstract

Melatonin, the hormone of the pineal gland, possesses a range of physiological functions, and recently, its anticancer effect has become more apparent. A more thorough understanding of molecular alterations in the components of several signaling pathways as new targets for cancer therapy is needed because of current innate restrictions such as drug toxicity, side effects, and acquired or de novo resistance. The PI3K/Akt/mTOR pathway is overactivated in many solid tumors, such as breast and ovarian cancers. This pathway in normal cells is essential for growth, proliferation, and survival. However, it is an undesirable characteristic in malignant cells. We have reviewed multiple studies about the effect of melatonin on breast and ovarian cancer, focusing on the PI3K/Akt/mTOR pathway. Melatonin exerts its inhibitory effects via several mechanisms. A: Downregulation of downstream or upstream components of the signaling pathway such as phosphatase and tensin homolog (PTEN), phosphatidylinositol (3,4,5)-trisphosphate kinase (PI3K), p-PI3K, Akt, p-Akt, mammalian target of rapamycin (mTOR), and mTOR complex1 (mTORC1). B: Apoptosis induction by decreasing MDM2 expression, a downstream target of Akt, and mTOR, which leads to Bad activation in addition to Bcl-XL and p53 inhibition. C: Induction of autophagy in cancer cells via activating ULK1 after mTOR inhibition, resulting in Beclin-1 phosphorylation. Beclin-1 with AMBRA1 and VPS34 promotes PI3K complex I activity and autophagy in cancer cells. The PI3K/Akt/mTOR pathway overlaps with other intracellular signaling pathways and components such as AMP-activated protein kinase (AMPK), Wnt/β-catenin, mitogen-activated protein kinase (MAPK), and other similar pathways. Cancer therapy can benefit from understanding how these pathways interact and how melatonin affects these pathways.

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褪黑素通过靶向 PI3K/Akt/mTOR 通路对乳腺癌和卵巢癌产生影响。
褪黑激素是松果体的激素,具有多种生理功能,最近,它的抗癌效果越来越明显。由于目前存在药物毒性、副作用、获得性或新生抗药性等先天限制,因此需要更透彻地了解作为癌症治疗新靶点的几种信号通路成分的分子变化。在乳腺癌和卵巢癌等许多实体瘤中,PI3K/Akt/mTOR 通路被过度激活。正常细胞的这一途径对于生长、增殖和存活至关重要。然而,它在恶性细胞中却是一种不理想的特性。我们回顾了有关褪黑激素对乳腺癌和卵巢癌影响的多项研究,重点关注 PI3K/Akt/mTOR 通路。褪黑素通过几种机制发挥其抑制作用。A:下调信号通路的下游或上游成分,如磷酸酶和天丝同源物(PTEN)、磷脂酰肌醇(3,4,5)-三磷酸激酶(PI3K)、p-PI3K、Akt、p-Akt、哺乳动物雷帕霉素靶标(mTOR)和 mTOR complex1(mTORC1)。B:通过降低 MDM2(Akt 的下游靶标)和 mTOR 的表达诱导细胞凋亡,除了抑制 Bcl-XL 和 p53 外,还导致 Bad 激活。C:抑制 mTOR 后,通过激活 ULK1 诱导癌细胞自噬,导致 Beclin-1 磷酸化。Beclin-1 与 AMBRA1 和 VPS34 可促进癌细胞中 PI3K 复合物 I 的活性和自噬。PI3K/Akt/mTOR 通路与其他细胞内信号通路和成分重叠,如 AMPK、Wnt/β-catenin、丝裂原活化蛋白激酶(MAPK)和其他类似通路。了解这些通路如何相互作用以及褪黑激素如何影响这些通路,对癌症治疗大有裨益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
IUBMB Life
IUBMB Life 生物-生化与分子生物学
CiteScore
10.60
自引率
0.00%
发文量
109
审稿时长
4-8 weeks
期刊介绍: IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.
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