Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Chem Biol Drug Des. 2019 Dec;94(6):2084-2093. doi: 10.1111/cbdd.13615. Epub 2019 Sep 20.
Hepatocellular carcinoma is one of the most pervasive cancers with low prognosis, high frequency of recurrence, and metastasis. Studies conducted have focused on extricating novel strategies for successful treatment. Kojic acid and its derivatives are already proven to have depigmenting, anti-inflammatory, and anti-neoplastic properties. In the present study, kojic acid and its 10 distinct derivatives were tested on HEPG2 cell line for their possible anti-cancer effect and seven of them were observed to be cytotoxic. Compound 6 was chosen to proceed as the IC dosage for HEPG2 cells was lower in comparison with the other derivatives and kojic acid itself. Further experiments pointed out that intrinsic apoptotic pathway was triggered with the exposure of the cells to IC concentration of the derivative as the treatment led to escalation of intracellular ROS, induction of TP53 gene, and activation of caspase 3/7. Pro-apoptotic Jnk and Bax genes were not triggered suggesting that the apoptotic pathway advance through an alternative route. Complementary experiments are in need; howbeit, the current findings suggest that the derivative offers a novel promising approach against hepatocellular carcinoma as it is not detrimental to healthy cells within the concentrations applied, and it does not induce drug resistance.
肝细胞癌是预后最差、复发和转移频率最高的癌症之一。已有的研究集中在寻找新的治疗策略上。曲酸及其衍生物已被证明具有美白、抗炎和抗肿瘤的特性。在本研究中，曲酸及其 10 种不同的衍生物在 HEPG2 细胞系上进行了测试，以观察它们是否具有抗癌作用，其中 7 种具有细胞毒性。选择化合物 6 作为 IC 剂量，因为与其他衍生物和曲酸本身相比，它对 HEPG2 细胞的 IC 剂量更低。进一步的实验表明，细胞内 ROS 的增加、TP53 基因的诱导和 caspase 3/7 的激活触发了内在的凋亡途径。促凋亡的 Jnk 和 Bax 基因没有被触发，这表明凋亡途径是通过另一种途径进行的。需要进行补充实验；然而，目前的研究结果表明，该衍生物为治疗肝细胞癌提供了一种新的有前途的方法，因为它在应用的浓度范围内对健康细胞没有损害，也不会诱导耐药性。
