Natural Compound Allicin Containing Thiosulfinate Moieties as Transmembrane Protein 16A (TMEM16A) Ion Channel Inhibitor for Food Adjuvant Therapy of Lung Cancer

Abstract

Cancer is one of the most serious malignant diseases, and chemotherapy is cancer's main clinical treatment method. However, chemotherapy inevitably produces drug resistance, and side effects accompany them. Adjuvant therapy is an effective way to enhance chemotherapeutic drug sensitivity and reduce side effects. This study found allicin, garlic's active ingredient, is an inhibitor of transmembrane protein 16A (TMEM16A), a novel drug target of lung adenocarcinoma. Allicin concentrationdependently inhibited TMEM16A currents with an IC 50 of 24.35 ± 4.14 μM. Allicin thiosulfinate moieties bound with R535A/ E624A/E633A residues of TMEM16A blocked the ion transport function and downregulated TMEM16A protein expression affecting the mitogen-activated protein kinase signal transduction. Then, allicin reduced the viability and migration of LA795 cells, and induced cell apoptosis. Moreover, multitarget combination administration results indicated that the therapeutic effect of 3.56 mg/kg allicin and 3 mg/kg cisplatin combined administration was superior to the superposition of the two drugs alone, demonstrating that the anticancer effects of allicin and cisplatin were synergistic. In addition, low-concentration combined administration also avoided the side effects of cisplatin in mice. Based on the good tumor suppressor effect and high biosafety of allicin and cisplatin combination in vivo, allicin can be used for food adjuvant therapy of cisplatin chemotherapy.

Allicin inhibits the biological activities of cervical cancer cells by suppressing circEIF4G2

“…Reducing the invasion and metastasis rates of tumor cells can improve clinical efficacy (Liu et al., 2018 ; Xie et al., 2022 ). Allicin is an herb extract that was previously reported to have antitumor effects against lung cancer (Bai et al., 2023 ), but its effects on CC are still unclear. Present study revealed allicin significantly reduced invasion and metastasis rates of Hela and Siha cells, with excellent inhibitory effects at high concentrations.…”

Astaxanthin Augmented the Anti‐Hepatocellular Carcinoma Efficacy of Sorafenib Through the Inhibition of the JAK2/STAT3 Signaling Pathway and Mitigation of Hypoxia within the Tumor Microenvironment

“…[ 2–5 ] The incorporation of dietary modifications as a supplementary approach to conventional cancer treatment is receiving considerable attention due to its practicality. [ 6,7 ]…”