Rasool Fayyaz, Sharma Deepu, Anand P Shanmukha, Magani Skj, Tantravahi Srinivasan
Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Greater Noida, India.
Department of Biotechnology, GITAM Institute of Science, Gandhi Institute of Technology and Management (GITAM) Deemed to be University, Visakhapatnam, India.
Front Pharmacol. 2021 Sep 20;12:698375. doi: 10.3389/fphar.2021.698375. eCollection 2021.
Chemotherapy is a general treatment procedure for cancer. The diversity in cancer incidence and the failure of therapy due to chemoresistance lead to increased cancer-related deaths. Therefore, new drugs with fewer secondary complications targeting diverse pathways are the need of the hour. Geranyl isovalerate (GIV), one of the active ingredients of ethyl acetate fraction of is routinely used as a food flavoring agent. In this study, we found that GIV also exhibits anticancer activity when tested against the HCT116 cell line. It influenced the viability of the cells in a dose- and time-dependent manner. We examined whether GIV could induce oxidative stress and affect the mitochondrial membrane potential, thereby leading to apoptosis induction. Moreover, GIV could suppress the expression of antiapoptotic genes, such as BCl2 and PARP, and induce the expression of proapoptotic genes, such as Caspase 3 and 9. This is the first study demonstrating the anticancer activity of GIV and providing evidence for its mechanism of action. In conclusion, this study proposes GIV as a potential lead or supplementary molecule in treating and preventing colorectal cancer (CRC). Based on our findings, we conclude that GIV may be a viable lead or supplementary molecule for treating and preventing CRC.
化疗是一种针对癌症的常规治疗方法。癌症发病率的多样性以及化疗耐药导致的治疗失败致使癌症相关死亡人数增加。因此，当下急需针对多种途径且副作用较少的新型药物。香叶基异戊酸酯（GIV）是[具体物质]乙酸乙酯馏分的活性成分之一，常被用作食品调味剂。在本研究中，我们发现GIV在针对HCT116细胞系进行测试时也表现出抗癌活性。它以剂量和时间依赖性方式影响细胞活力。我们研究了GIV是否能诱导氧化应激并影响线粒体膜电位，从而导致细胞凋亡。此外，GIV可抑制抗凋亡基因如BCl2和PARP的表达，并诱导促凋亡基因如Caspase 3和9的表达。这是第一项证明GIV抗癌活性并为其作用机制提供证据的研究。总之，本研究提出GIV作为治疗和预防结直肠癌（CRC）的潜在先导或辅助分子。基于我们的研究结果，我们得出结论，GIV可能是治疗和预防CRC的可行先导或辅助分子。
