Guruswamy Dileep Kumar M, Balaji Kyathegowdana Doddi Srivinavasa, Dharmappa Kattepura Krishnappa, Jayarama Shankar
Department of Biotechnology, Teresian College, Siddhartha Nagara Mysore-570011, Karnataka, India.
Department of Studies in Biochemistry, Mangalore University, Chikkaaluvara, Kodagu-571232, Karnataka, India.
Oncotarget. 2020 Dec 15;11(50):4661-4676. doi: 10.18632/oncotarget.27836.
In the present investigation, we synthesized chalcone bearing naphthalene compound d1, and on the basis of H-NMR, C NMR, and LC-MS data we had specified the structure of the synthesized compound. The resultant compound d1 was assessed for their antiproliferative action against human cancer cell lines (HeLa, HCT116, HT29, MDA-MB-231, MCF-7, and SKBR3). The IC range was estimated at 5.58 to 11.13 μM shows that compound d1 had remarkable anticancer activity on HeLa cell lines. Besides, it was discovered that d1 incited the mitochondrial apoptotic pathway by controlling Bax and Bcl-2 transcripts by expanding the Caspase 3 activation. We depicted the effects of tumor advancement and the antiangiogenic activity of d1 in the EAC animal model. Tumor growth had inhibited and without symptoms the longevity of EAC containing mice expanded by the treatment of d1. Inhibition of nuclear transcriptional factor HIF-1α in EAC cells and finally it also inhibited phosphorylation of downstream signaling proteins such as ERK, p38, and JNK in HeLa cells. The present investigation uncovered that d1 indicated noteworthy tumor-repressing abilities much less concentration in and recommended that compound d1 as the potent anticancer medication.
在本研究中，我们合成了含萘的查尔酮化合物d1，并根据氢核磁共振（H-NMR）、碳核磁共振（C NMR）和液相色谱-质谱（LC-MS）数据确定了合成化合物的结构。对所得化合物d1针对人癌细胞系（HeLa、HCT116、HT29、MDA-MB-231、MCF-7和SKBR3）的抗增殖作用进行了评估。估计其半数抑制浓度（IC）范围为5.58至11.13 μM，表明化合物d1对HeLa细胞系具有显著的抗癌活性。此外，还发现d1通过增加半胱天冬酶3的激活来控制Bax和Bcl-2转录本，从而引发线粒体凋亡途径。我们描述了d1在艾氏腹水癌（EAC）动物模型中对肿瘤进展的影响和抗血管生成活性。d1治疗可抑制肿瘤生长，且含EAC的小鼠在无症状的情况下寿命延长。d1抑制EAC细胞中的核转录因子缺氧诱导因子-1α（HIF-1α），最终还抑制HeLa细胞中细胞外信号调节激酶（ERK）、p38和c-Jun氨基末端激酶（JNK）等下游信号蛋白的磷酸化。本研究发现，d1在低得多的浓度下就显示出显著的肿瘤抑制能力，并推荐化合物d1作为一种有效的抗癌药物。
