Inhibition of Dormant Lung Cancer Cell Reactivation by Punica Granatum Peel and Dioscorea Nipponica: Involving MYC, SKP2 and p27.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-05-15 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S494168

Su Su Thae Hnit, Ling Bi, Chanlu Xie, Ling Xu, Yi Zhong, Ming Yang, Yan Wang, Qihan Dong

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引用次数: 0

Abstract

Introduction: Dormant cancer cells, capable of reactivating from the G₀ phase, drive tumor recurrence and therapy resistance. Current clinical strategies targeting dormancy remain limited. This study evaluates Punica granatum peel (PGP) and Dioscorea Nipponica (DN) for their ability to sustain dormancy in lung cancer cells and inhibit reactivation.

Methods: Dormancy was induced in A549 and H460 lung cancer cells via contact inhibition or serum deprivation. Subcutaneous and orthotopic xenograft mouse models were employed. Cells and mice were treated with PGP, DN, or their combination. SYBR Green assays, flow cytometry, and immunoblotting assessed DNA synthesis, cell cycle phases, and protein expression (p27, SKP2, cMYC, AURORA A, SUPT16H, SSRP1).

Results: Both PGP and DN significantly inhibited DNA synthesis and cell cycle re-entry (G₀-to-G₁ transition) in vitro. In vivo, tumor volume and weight decreased by 26-50% (p < 0.05) in treated mice. Treatments upregulated p27 while downregulating SKP2, cMYC, AURORA A, SUPT16H, and SSRP1. No synergistic effect was observed, but additive efficacy (Combination Index ≈1) was noted at a 10:1 PGP:DN ratio.

Discussion: PGP and DN sustain dormancy by modulating key cell cycle regulators, highlighting their potential to reduce recurrence and combat drug resistance. These findings underscore the therapeutic promise of traditional Chinese medicines in managing dormant cancer cells. Future studies should identify active compounds and validate mechanisms in advanced models.

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石榴皮和薯蓣对休眠肺癌细胞活化的抑制作用：涉及MYC、SKP2和p27。

休眠癌细胞，能够从G0期重新激活，驱动肿瘤复发和治疗抵抗。目前针对休眠的临床策略仍然有限。本研究评估了石榴皮（PGP）和薯蓣（DN）在肺癌细胞中维持休眠和抑制再激活的能力。方法：采用接触抑制法和血清剥夺法诱导A549和H460肺癌细胞休眠。采用皮下和原位异种移植小鼠模型。细胞和小鼠分别接受PGP、DN或它们的联合治疗。SYBR Green法、流式细胞术和免疫印迹法评估DNA合成、细胞周期分期和蛋白表达（p27、SKP2、cMYC、AURORA A、SUPT16H、SSRP1）。结果：PGP和DN均能显著抑制体外DNA合成和细胞周期再进入（g2 - g1过渡）。体内治疗组小鼠肿瘤体积和重量减少26 ~ 50% （p < 0.05）。处理上调p27，下调SKP2、cMYC、AURORA A、SUPT16H和SSRP1。在PGP:DN比为10:1时，无增效作用，但有加性效应（联合指数≈1）。讨论：PGP和DN通过调节关键的细胞周期调节因子来维持休眠，突出了它们减少复发和对抗耐药性的潜力。这些发现强调了传统中药在治疗休眠癌细胞方面的治疗前景。未来的研究应该在先进的模型中确定活性化合物并验证机制。

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

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.