Goel Yugal, Yadav Saveg, Pandey Shrish Kumar, Temre Mithlesh Kumar, Maurya Babu Nandan, Verma Ashish, Kumar Ajay, Singh Sukh Mahendra
School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, India.
Department of Radiodiagnosis and Imaging, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Front Oncol. 2021 Feb 25;11:619351. doi: 10.3389/fonc.2021.619351. eCollection 2021.
Methyl jasmonate (MJ), a natural oxylipin, possesses a broad spectrum of antineoplastic potential . However, its tumor growth impeding and chemo-potentiating action has not been adequately investigated . Using a murine thymus-derived tumor named Dalton's Lymphoma (DL), in the present study, we examined if intra-tumoral administration of MJ can cause tumor growth impedance. We also explored the associated molecular mechanisms governing cell survival, carbohydrate & lipid metabolism, chemo-potentiation, and angiogenesis. MJ administration to tumor-transplanted mice caused deceleration of tumor growth accompanying prolonged survival of the tumor-bearing mice. MJ-dependent tumor growth retardation was associated with the declined blood supply in tumor milieu, cell cycle arrest, augmented induction of apoptosis and necrosis, deregulated glucose and lipid metabolism, enhanced membrane fragility of tumor cells, and altered cytokine repertoire in the tumor microenvironment. MJ administration modulated molecular network implicating Hsp70, Bcl-2, TERT, p53, Cyt , BAX, GLUT-1, HK 2, LDH A, PDK-1, HIF-1α, ROS, MCT-1, FASN, ACSS2, SREBP1c, VEGF, cytokine repertoire, and MDR1, involved in the regulation of cell survival, carbohydrate and fatty acid metabolism, pH homeostasis, and drug resistance. Thus, the present study unveils novel molecular mechanisms of the tumor growth decelerating action of MJ. Besides, this preclinical study also establishes the adjunct therapeutic potential of MJ. Hence, the present investigation will help to design novel anti-cancer therapeutic regimens for the treatment of hematological malignancies.
茉莉酸甲酯（MJ）是一种天然的氧脂素，具有广泛的抗肿瘤潜力。然而，其对肿瘤生长的抑制作用和化疗增敏作用尚未得到充分研究。在本研究中，我们使用一种源自小鼠胸腺的肿瘤——道尔顿淋巴瘤（DL），来检测肿瘤内注射MJ是否会导致肿瘤生长受到抑制。我们还探讨了与之相关的调控细胞存活、碳水化合物和脂质代谢、化疗增敏以及血管生成的分子机制。给肿瘤移植小鼠注射MJ导致肿瘤生长减速，同时荷瘤小鼠的生存期延长。MJ依赖性的肿瘤生长迟缓与肿瘤微环境中血液供应减少、细胞周期停滞、凋亡和坏死诱导增加、葡萄糖和脂质代谢失调、肿瘤细胞膜脆性增强以及肿瘤微环境中细胞因子谱改变有关。注射MJ调节了涉及热休克蛋白70（Hsp70）、B细胞淋巴瘤-2（Bcl-2）、端粒酶逆转录酶（TERT）、p53、细胞色素（Cyt）、Bcl-2相关X蛋白（BAX）、葡萄糖转运蛋白1（GLUT-1）、己糖激酶2（HK 2）、乳酸脱氢酶A（LDH A）、丙酮酸脱氢酶激酶1（PDK-1）、缺氧诱导因子-1α（HIF-1α）、活性氧（ROS）、单羧酸转运蛋白1（MCT-1）、脂肪酸合酶（FASN）、乙酰辅酶A合成酶2（ACSS2）、固醇调节元件结合蛋白1c（SREBP1c）、血管内皮生长因子（VEGF）、细胞因子谱以及多药耐药蛋白1（MDR1）的分子网络，这些分子参与调控细胞存活、碳水化合物和脂肪酸代谢、pH稳态以及耐药性。因此，本研究揭示了MJ抑制肿瘤生长作用的新分子机制。此外，这项临床前研究还确立了MJ的辅助治疗潜力。因此，本研究将有助于设计用于治疗血液系统恶性肿瘤的新型抗癌治疗方案。
