The Synergistic Antitumor Effect of 5-Fluorouracil Combined with Allicin against Lung and Colorectal Carcinoma Cells

Abstract

5-fluorouracil (5-FU) is an anticancer drug used to inhibit the proliferation of many different tumor cells. Since severe events are associated with this compound, its combination with different anticancer drugs or adjuvants would allow the use of a significantly lower dose of 5-FU. In this study, we highlighted that the combination of allicin with 5-FU inhibited the cell migration and proliferation of colorectal and lung cancer cells. 5-FU inhibited cell growth with a similar inhibitory concentration for both normal and tumor cells (~200µM), while allicin showed different inhibitory concentrations. With an IC50 of 8.625 µM, lung cancer cells were the most sensitive to allicin. Compared to 5-FU and allicin single-agent treatments, the co-treatment showed a reduced viability rate, with p < 0.05. The morphological changes were visible on all three cell lines, indicating that the treatment inhibited the proliferation of both normal and tumor cells. We highlighted different cell death mechanisms—apoptosis for lung cancer and a non-apoptotic cell death for colorectal cancer. The synergistic antitumor effect of 5-FU combined with allicin was visible against lung and colorectal carcinoma cells. Better results were obtained when a lower concentration of 5-FU was combined with allicin than the single-agent treatment at IC50.

Phytochemical Analysis and In Vitro Effects of Allium fistulosum L. and Allium sativum L. Extracts on Human Normal and Tumor Cell Lines: A Comparative Study

“…The antitumoral effect of garlic induced by its bioactive sulfur compounds like allicin, diallyl-sulfides (DAS), diallyl-disulfides (DADS), and diallyl-trisulfides (DATS), raises interest for many studies [ 11 , 12 , 13 ]. DATS can stimulate cytotoxicity by targeting reactive oxygen species (ROS) and can activate the ROS dependent caspase pathway, therefore it can promote apoptosis [ 14 ].…”

“…Allicin is the result of hydrolyzed alliin under alliinase enzyme action, with ajoene as a secondary compound resulted after alliin decomposition [ 15 , 19 ]. Allicin has an immunostimulatory effect [ 19 ] and antitumoral properties by inhibiting cell proliferation, migration, and enhancing apoptosis [ 12 , 20 , 21 , 22 ]. The antitumor effect of allicin was investigated on different tumor cell lines like cervical cancer, breast cancer, colorectal cancer, gastric cancer, glioblastoma, leukemia, lymphoma, and endometrial adenocarcinoma [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

Predictive value of clinical toxicities of chemotherapy with fluoropyrimidines and oxaliplatin in colorectal cancer by DPYD and GSTP1 gene polymorphisms

“…Falzacappa et al demonstrated combined uorouracil and rucaparib able to enhance the e cacy and speci city of acute myeloid leukemia [13]. Adrian BogdanTigu et al highlighted that the combination of allicin with 5-FU has an obvious against lung and colorectal cancer effect while reducing the dosage of uorouracil [14]. For breast cancer, uorouracil (5-FU) is widely used and a growing number of physicians are using capecitabine as rst-line or second-line chemotherapy [15].…”

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation

“…Allicin revealed a synergistic anticancer activity with 5-fluorouracil against lung and colorectal carcinoma cells [115], as well as sensitizing hepatocellular cancer cells to 5-fluorouracil [116]. It was S S O Alliin is a sulfoxide that represents 80% of the cysteine sulfoxides in garlic and is considered the allicin precursor molecule.…”

“…Allicin revealed a synergistic anticancer activity with 5-fluorouracil against lung and colorectal carcinoma cells [115], as well as sensitizing hepatocellular cancer cells to 5-fluorouracil [116]. It was reported that allicin can effectively hinder cell growth of U251 glioma cells [117] and reduces tumor burden in breast cancer cells [118,119].…”