Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 21, Issue 18, 2021

Doxorubicin (DOX) is widely used as a clinical first-line anti-cancer drug. However, its clinical application is severely limited due to the lack of tumor specificity of the drug and severe side effects such as myelosuppression, nephrotoxicity, dose-dependent cardiotoxicity, and multi-drug resistance. To improve the bioavailability of DOX, maximize the therapeutic effect, and reduce its toxicity and side effects, many studies have been done on the nanoformulations of DOX, such as liposomes, polymer micelles, dendrimer, and nanogels. Herein, we review the latest progress of DOX nano-preparations and their anti-tumor effects, hoping to provide theoretical references and new research ideas for the development of new dosage forms of the drug and the technical methods available for clinical application.

Urothelial carcinoma has become the ninth most common malignancy in the world. Since the 1980s, diverse studies and treatment methods came out with their possible effects along with certain limitations. Initially, platinum chemotherapy was considered as first-line treatment of the disease. Although it was proved to be effective initially, the most number of cases reported the reoccurrence of the disease. Furthermore, aberrant ligand- dependent and constitutive ligand-independent fibroblast growth factor receptor (FGFR) signaling has been reported in a large number of solid tumors, including urothelial carcinoma that became the basis for FGFR inhibition for the treatment of the disease. Erdafitinib is a pan-FGFR inhibitor that was recently approved in the USA for the treatment of locally advanced or metastatic FGFR3 or FGFR2 urothelial carcinoma. The drug is also being investigated as a treatment for other cancers, including cholangiocarcinoma, liver cancer, non-small cell lung cancer, prostate cancer, lymphoma cancer and oesophageal cancer. This article summarizes the various treatments that evolved for bladder cancer till now, a brief description of the biology of FGFR inhibition, clinical pharmacology, and various clinical trials of erdafitinib.

Background: Metal-organic frameworks (MOFs), as attractive hybrid crystalline porous materials, are being increasingly investigated in biomedical applications owing to their exceptional properties, including high porosity, ultrahigh surface areas, tailorable composition and structure, and tunability and surface functionality. Of interest, in this review, is the design and development of MOF-based drug delivery systems (DDSs) that have excellent biocompatibility, good stability under physiological conditions, high drug loading capacity, and controlled/targeted drug release. Objective: This review highlights the latest advances in MOFs as anticancer drug delivery systems (DDSs) along with insights on their design, fabrication, and performance under different stimuli that are either internal or external. The synthesis methods of MOFs, along with their advantages and disadvantages, are briefly discussed. The emergence of multifunctional MOF-based theranostic platforms is also discussed. Finally, the future challenges facing the developments of MOFs in the field of drug delivery are discussed. Methods: The review was prepared by carrying out a comprehensive literature survey using relevant work published in various scientific databases. Results: Novel MOFs in biomedical applications, especially in drug delivery, have shown great potential. MOF-based DDSs can be classified into normal (non-controllable) DDSs, stimuli-responsive DDSs, and theranostic platforms. The normal DDSs are pristine MOFs loaded with therapeutic agents and offer little to no control over drug release. Stimuli-responsive DDSs offer better spatiotemporal control over drug release by responding to either endogenous (pH, redox, ions, ATP) or exogenous stimuli (light, magnetism, US, pressure, temperature). The theranostic platforms combine stimuli-responsive drug delivery with diagnostic imaging functionality, paving the road for imaging-guided drug delivery. Conclusion: This review presented a summary of the various methods utilized in MOF's synthesis along with the advantages and disadvantages of each method. Furthermore, the review highlighted and discussed the latest developments in the field of MOF-based DDSs and theranostic platforms. The review is focused on the characteristics of MOF-based DDSs, the encapsulation of different anticancer drugs as well as their stimuli-responsive release.

Aim: The aim of our research work is the synthesis of tetrahydroisoquinoline derivatives as anti-Angiogenesis and anti-cancer agents. Background: Cancer is the second leading cause of deaths in the United States. The current recovery rate from the advanced treatment for the cancer is excessively low. Therefore, the identification of novel, potent, and less toxic anticancer agents remains a top priority. Objective: To evaluate anti-angiogenesis and anticancer activities of THIQs on different colorectal cancer cell lines (CRC) viz., Colo320, DLD-1, HCT116, SNU-C1, SW480, and GSK3b in pre-treated viability HCT116. and to carry out molecular docking studies of THIQs. Methods: Twenty synthesized THIQs were screened in the Eli Lilly’s Open Innovation Drug Discovery Program and selected twelve compounds for in vitro primary screening in the KRas (Kirsten rat sarcoma)-Wnt SL (Synthetic Lethal) in the basal viability of different colon cancer cell lines. Docking studies of the active THIQs were also performed in our laboratory, targeting the active sites of KRas and VEGF receptors. Results: Compound GM-3-18 was found to possess significant activities for KRas inhibition, with IC50 values in the range of 0.9 μM to 10.7 μM, for all colon cancer cell lines. Compound GM-3-121 showed potent anti-angiogenesis activity with IC50 = 1.72 μM. Molecular docking studies showed that the carbonyl oxygen atoms of GM-3-18 and GM-3-121 showed hydrogen bonding interactions with the hydrogen of - OH groups of THR 74 (A). Conclusion: The results indicated that all the compounds showed moderate to high activity for KRas inhibition. The THIQs bearing the chloro group at the 4-position of the phenyl ring (GM-3-18) exhibited significant KRas inhibition against all colon cancer cell lines.

Background: Medicinal plants serve as sources of compounds used to treat other types of cancers. The root of the plant Lophira alata (Ochnaceae) has been used as a component of traditional herbal decoctions administered to cancer patients in southwestern Nigeria. However, the mechanism of the cytotoxic effects of Lophira alata alone or in the presence of phorbol ester has not been investigated in brain tumor cells. Objective: This study aimed to examine the cytotoxic potential of the methanolic fraction of Lophira alata root on malignant glioma invasive cellular growth and survival. Methods: The methanolic fraction of Lophira alata (LAM) was subjected to high-performance liquid chromatography to determine the fingerprints of the active molecules. The antiproliferative effects of Lophira alata were assessed using the MTT and LDH assays. Protein immunoblots were carried out to test the effects of Lophira alata, alone or in the presence of phorbol ester, on survival signaling pathways, such as Akt, mTOR, and apoptotic markers such as PARP and caspases. Results: The methanolic fraction of Lophira alata (LAM) induced a concentration-dependent and time-dependent decrease in glioma cell proliferation. In addition, LAM attenuated phorbol ester-mediated signaling of downstream targets such as Akt/mTOR. Gene silencing using siRNA targeting PKC-alpha attenuated LAM-mediated downregulation of Akt. In addition, LAM induced both PARP and caspase cleavages. The HPLC fingerprint of the fraction indicates the presence of flavonoids. Conclusion: LAM decreases cell proliferation and induces apoptosis in glioma cell lines and thus could serve as a therapeutic molecule in the management of gliomas.

Background: Breast cancer (BC) is increasingly becoming the primary reason for death in women, which sounded the alarm. Thus, finding a novel management target for BC is imminent. Methods: The data of gene expression and clinicopathological characteristics were downloaded from The Cancer Genome Atlas (TCGA). The expression of nuclear receptor co-activator 5 (NCOA5) in 35 paired breast cancer and adjacent tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Univariate and Multivariate logistic regression methodology was applied to analyze the prognostic factors for lymph node metastasis (LNM). Based on the status of breast cancer-relative receptors, patients were distributed in six groups, then the Kaplan-Meier survival analysis with log-rank test was applied to investigate the involvement among the expression of NCOA5 and overall survival (OS). Results: The expression of NCOA5 in BC was greater than normal tissues when comparing the data from TCGA. This result had also been verified in our local cohort. The expression of NCOA5 was closely related to LNM, Estrogen receptor (ER) status and progesterone receptor (PR) status. The consequence of Multivariate logistic regression analysis showed that the expression of NCOA5, tumor size, ER status and clinical stage was significantly associated with LN. Moreover, subgroup analyses showed that high expression of NCOA5 is an independent risk factor for OS in patients who were in ER (+) or PR (+) or maybe human epidermal growth factor receptor-2(Her-2) positive status. Conclusion: NCOA5 was significantly correlated with LNM in BC. Meanwhile, the expression of NOCA5 could predict the OS time, especially in breast cancer patients whose status of hormone receptor was positive. NCOA5 may act as a promising treatment target to shortening the treatment period and improving the prognosis of ER (+) breast cancer.

Background: Alantolactone (AL) is a natural compound extracted from the roots of Inula Helenium L, which exerts an anti-tumor effect in a variety of cancer cell lines; however, its effect on esophageal cancer, a common malignancy with poor prognosis, remains unclear. Therefore, we aim to evaluate the effect of AL on esophageal cancer and to explore its underlying mechanism. Objective: This study aims to determine whether AL has an anti-cancer effect on esophageal cancer cells and to explore its underlying mechanism. Methods: The effect of AL on the proliferation and apoptosis of esophageal cancer cells was detected by MTT assay, colony formation assay, crystal violet assay, flow cytometry and hoechst apoptosis staining. The wound healing and Transwell invasion assay were performed to examine the effect of AL on the migration and invasion of esophageal cancer cells. Luciferase reporter system and Western blot were used to study the anti-tumor mechanism of AL on esophageal cancer cells. The subcutaneous murine xenograft model was employed to verify the effects of AL on esophageal cancer cells. Results: MTT assay, colony formation assay and crystal violet assay found that AL inhibited the growth of esophageal cancer cells. Hoechst staining and flow cytometry analysis showed that AL induced apoptosis in esophageal cancer through mitochondrial pathway. Transwell assay and wound healing assays showed that AL inhibited the metastasis and invasion of esophageal cancer cells. Wnt/ β-catenin signaling may contribute to the mechanism of the inhibition. The anti-tumor effect of AL on esophageal cancer cells was validated on murine xenograft model. Conclusion: Our data indicate that AL inhibits proliferation, migration, and invasion of esophageal cancer cells, and promote apoptosis of esophageal cancer cells through the Wnt/β-catenin signaling pathway.

Background: Cervical cancer is the second leading cause of cancer in women, which necessitates safe and potential therapeutic agents. Objective: This study was designed to investigate the antiproliferative effect of ethanolic extract of Cissus quadrangularis L. (CQ) against human cervical adenocarcinoma HeLa cell line and in silico analysis of selected active agents against apoptosis executioner enzyme caspase-3. Methods: Cell viability was analyzed in HeLa cells at different concentrations (25-300 μg/ml) of CQ extract. Reactive oxygen species (ROS) generation, cellular apoptosis, cell cycle analysis and caspases-3 activation were evaluated. In silico, structure-based virtual screening analysis was carried out using AutoDock Vina and iGEMDOCK. Results: Cell viability of HeLa cells was reduced significantly (p < 0.05) in a dose-dependent manner, however, CQ extract showed non-toxic to normal kidney epithelial NRK-52E cells. CQ extract induced the intracellular ROS level, nuclear condensation and reduced the mitochondrial membrane potential (MMP) with the induction of annexin V-FITC positive cells. CQ extract arrested cells in G0/G1 and G2/M checkpoints and activated caspase-3 activity significantly in HeLa cells. The molecular docking study showed a strong binding affinity of CQ phytocomponents against the caspase-3 (PDB ID: 1GFW) protein of human apoptosis. PASS analyses of selected active components using Lipinski’s Rule of five showed promising results. Further, drug-likeness and toxicity assessment using OSIRIS Data Warrior V5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. Conclusion: This study suggested that active constituents in CQ extract can be considered as potential chemotherapeutic candidates in the management of cervical cancer.

Background: To evaluate the chemopreventive potential of boldine against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in Wistar albino rats. Objective: Boldine is an alkaloid isolated from Peumus boldus. The primary active constituents of boldine exhibited several potential medicinal properties. The present study was evaluated to explore the chemopreventive agent of boldine on anti-proliferative efficacy against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in Wistar albino rats. Methods: The effect of boldine on cellular proliferative markers, i.e., PCNA and Ki67on hepatocellular carcinoma rats was determined by immuno expression study. Liver marker enzymes, tumor biomarker, oxidative stress markers, antioxidant status, and xenobiotic phase I and II enzymes in HCC rats were analyzed. Moreover, cell cycle proteins, i.e., p21^Cip1/Kip1, p27 ^Cip1/Kip1, Cyclin D1, CDK 4, Cyclin E1, and CDK 2 were investigated using immuno expression analysis. Results: Treatment of boldine protected the liver against reactive oxygen species such as hydrogen peroxide, superoxide, protein carbonyl, and lipid peroxide during hepatocarcinogenesis by boosted antioxidants-superoxide dismutase (SOD), catalase (CAT). Boldine caused a substantial enhanced detoxification process by moderating phase I and II xenobiotic-metabolizing enzymes. Besides, the study found that boldine significantly inhibited the cellular proliferative markers like PCNA and Ki67 and regulated the specific cell cycle-associated proteins by up-regulated expression of p21^Cip1/Kip1and p27 ^Cip1/Kip1 and down-regulated expression of Cyclin D1, CDK 4, Cyclin E1, and CDK 2. Conclusion: Our data manifests the anti-proliferative effect of boldine, which negatively modulates cellular proliferation and regulates cell cycle by protecting the cell from reactive oxygen species (ROS), suggesting that boldine establishes it as a chemopreventive agent in diethylnitrosamine-induced hepatocarcinogenesis in rats.

Background: Prostate cancer (PCa) has the second-highest morbidity and mortality rates in men. Possessing facile surface chemistry and unique optical properties make silica nanoparticles(SiO2-NPs) promising cancer therapy materials. Objective: This study aimed to investigate the effects of SiO2-NPs and their derivatives, including SiNP-NH2, SiNP-Cl, and SiNP-SH against PCa and clarify their molecular mechanism on cell death, gene, and protein expressions. Methods: Following the synthesis and derivation of SiO2-NPs, their characterization was carried out using TEM, DLS, BET, and FT-IR. Cytotoxic properties of the compounds were investigated against different human cancerous cells; including HUH-7, A549, DLD-1, HeLa, NCI-H295R, and PC-3, as well as human healthy epithelium cell line PNT1A. Results: SiNP-NH2, SiNP-Cl, and SiNP-SH dose-dependently inhibited the proliferation of PC-3 cells with an IC50 value as 55.46 μg/mL, 55.09 μg/mL and 72.89 μg/mL, respectively. SiNP-SH significantly(p<0.0001) inhibited metastasis and invasion of PC-3 cells(20.4% and 46.7%, respectively), and significantly(p<0.0001) increased early apoptosis(32.3%) when compared with non-treated cells. Protein and mRNA expressions of BcL-2, Bax, caspase-3, caspase-9, caspase-12, p53, Smad-4, Kras, and Nf-ĸB were also altered following the treatment of SiO2-NPs and its derivatives. Conclusion: Our results demonstrated that -SH functioned SiO2-NPs can prevent the proliferation of human PCa by increasing apoptosis by up-regulating gene and protein expression of p53(TP53) as well as caspase-3, caspase-9, and caspase-12 in the apoptotic pathway. Besides, the increased level of Smad-4 has also implicated the decreased cell proliferation. Hence, low sized SiNP-SH nanoparticles might be a suitable candidate for the treatment of human PCa.

Background: Green synthesis, an alternative method for synthesizing nanoparticles, is cheaper, environmentally friendly, and does not show toxic effects. Doxorubicin is a chemotherapeutic agent used in lung cancer. Curcumin is a bioactive compound with properties, such as an anticancer obtained from Curcuma longa. Objective: The objective of this study was to develop Doxorubicin and Curcumin loaded magnetic nanoparticles that could be synthesized by green tea leaves and to investigate cytotoxic effects against the A549-luc-C8, non-small cell lung cancer line. Methods: Magnetic nanoparticles were synthesized with the green synthesis method. Furthermore, Doxorubicin and Curcumin were encapsulated into magnetic nanoparticles with the one-pot method and obtained magnetic nanoparticles characterized using FTIR, SEM/EDX, XRD, and UV-VIS spectrophotometric techniques. After that, The drug release test was performed by dialysis using pH 7.4 phosphate-buffered saline at 37 °C. MTT assay was performed to test the cytotoxicity effect in the A549-luc-C8 cell line. Results: FTIR analysis verified the magnetic structure and drug loading. SEM images of magnetic nanoparticle revealed that they had a size of about 50-60 nm in a mono-disperse manner. Drug release after 24 h was found to be 5.8% for doxorubicin and 3.4% for curcumin, showing controlled release. Conclusion: Results showed that the prepared magnetic nanoparticles had a synergistic antitumor activity for A549-luc-C8.

Background: The plants of high phenolic contents are perfect antioxidant and anti-inflammatory agents and participate in biological studies as effective agents towards different cancer cell lines. Objective: To investigate the antioxidant, anti-inflammatory, and cytotoxic activities of the hydromethanolic leaf extract of Jasminum multiflorum (Burm. f.) Andrews. (J. multiflorum), and phenolic profiling of the extract. Methods: The antioxidant activity for the extract was estimated using β-Carotene-linoleic and Ferric Reducing Antioxidant Power (FRAP) assays. The anti-inflammatory activity was evaluated by histamine release assay. Cytotoxicity of J. multiflorum was performed using a neutral red uptake assay towards breast cancer (MCF-7) and colorectal cancer (HCT 116) cell lines. Phenolic profiling of the leaves was characterized using high performance liquid chromatography coupled to photodiode array detector-mass spectroscopy-mass spectroscopy (HPLC-PDA-MS/MS), and chromatographic isolation and identification of the isolated compounds were performed using spectroscopic and NMR data, and virtual docking was performed to the isolated compounds against HSP90 (HEAT SHOCK PROTEIN 90). Results: At a concentration of 75 μg mL-1, J. multiflorum extract showed high antioxidant power; 68.23±0.35 % inhibition and 60.30±0.60 a TEAC (μmol Trolox g-1) for β-Carotene-linoleic assay and FRAP assay; respectively, and possessed anti-inflammatory activity with IC50 67.2 μg/ml. J. multiflorum showed high cytotoxic activity with IC50 of 24.81 μg/ml and 11.38 μg/ml for MCF-7 and HCT 116 cell lines, respectively. HPLC-PDA-MS/MS analysis tentatively identified 39 compounds; major compounds are secoiridoid glycosides, kaempferol, and quercetin glycosides, in addition to simple phenylethanoid compounds. Isolation of active metabolites was performed and led to the isolation and identification of four compounds. On the basis of docking study using HSP90 legend, kaempferol neohesperidoside showed a high cytotoxic potential supported by a high affinity score towards HSP90 legend protein. Conclusion: Jasminum multiflorum is a good candidate to isolate cytotoxic agents.

Background: Heat shock protein90 (Hsp90) is overexpressed in tumor cells, thus the inhibition of the Hsp90 ATPase activity would be a meaningfully effective strategy in cancer therapy. Objective: The present work was aimed at four steps: designing new Hsp90 inhibitors as anti-cancer by a virtual screening study; synthesize designed compounds; biological evaluation of them and finally molecular dynamic (MD) simulations of best compounds. Methods: A virtual screening study was performed on a library (100 compounds) of the ZINC database with benzimidazole scaffold; then an extracted compound and two derivatives were synthesized. The anti-proliferative and ATPase inhibitory activities of these compounds were evaluated by MTT and ATPase inhibition assays, respectively. The western blot analysis was performed to the evaluation of the expression level of Hsp70 and Her2 proteins. Finally, 200 ns molecular dynamic simulation was carried out to confirm the stability of the strongest synthesized compound in Hsp90 active site. Results: ZINC00173501 compound with an aminobenzimidazole scaffold was chosen by the virtual screening study. ZINC00173501 compound and two of its derivatives were synthesized. ATPase inhibitory activity of three synthesized compounds shown that ZINC00173501 compound was the most potent inhibitor (IC50= 8.6 μM) with the anti-proliferative activity 14.41 μM, 19.07 μM and more than 100 μM against MCF-7, HeLa and HUVEC cell lines, respectively. The high level of Hsp70 expression and low level of Her2 expression confirmed ZINC00173501 as an Hsp90 inhibitor. Finally, molecular dynamics simulation showed that ZINC00173501 was stable in Hsp90 active site during 200 ns simulation. Conclusion: The biological evaluation results show that 2-aminobenzimidazole scaffold could be suggested as a lead for inhibition of Hsp90.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, with a 5- year survival rate of less than 10% because of the limited knowledge of tumor-promoting factors and their underlying mechanism. Diabetes mellitus (DM) and hyperglycemia are risk factors for many cancers, including PDAC, that modulate multiple downstream signaling pathways, such as the wingless/integrated (Wnt)/β-- catenin signaling pathway. However, whether hyperglycemia promotes PDAC initiation and progression by activating the Wnt/β-catenin signaling pathway remains unclear. Methods: In this study, we used bioinformatics analysis and clinical specimen analysis to evaluate the activation states of the Wnt/β-catenin signaling pathway. In addition, colony formation assays, Transwell assays and wound-healing assays were used to evaluate the malignant biological behaviors of pancreatic cancer cells (PCs) under hyperglycemic conditions. To describe the effects of hyperglycemia and the Wnt/β-catenin signaling pathway on the initiation of PDAC, we used pancreatitis-driven pancreatic cancer initiation models in vivo and pancreatic acinar cell 3-dimensional culture in vitro. Results: Wnt/β-catenin signaling pathway-related molecules were overexpressed in PDAC tissues/cells and correlated with poor prognosis in PDAC patients. In addition, hyperglycemia exacerbated the abnormal activation of β-catenin in PDAC and enhanced the malignant biological behaviors of PCs in a Wnt/β-catenin signaling pathway-dependent manner. Indeed, hyperglycemia accelerated the formation of precancerous pancreatic lesions by activating the Wnt/β-catenin signaling pathway in vivo and in vitro. Conclusion: Hyperglycemia promotes pancreatic cancer initiation and progression by activating the Wnt/β- catenin signaling pathway.

Background: Chemical synthesis methods are adverse in the medicinal field as they produce toxins on the surface area whereas green synthesis provide advancement are cost effective, environment friendly, can be easily scaled up for large scale synthesis. Silver and silver nanoparticles have an important application in the medical industry, such as tropical ointments which are used to prevent infection against burn and open wounds. There is no report on the green synthesis from Phlebodium aureum (L.) J. Smith. Objective: The present study was aimed to synthesize silver nano-particles using Phlebodium aureum (L.) J. Smith extracts by green approach and to screen their cytotoxicity. Methods: The synthesized AgNPs of P. aureum were characterized by FT-IR, SEM and XRD. The cytotoxicity of the aqueous extracts and AgNPs of P. aureum was determined. Results: The silver nanoparticle synthesis was confirmed by color change from yellow to dark brown and absorption peak at 460 nm. FT-IR analysis confirmed the capping by proteins and other metabolites. XRD analysis confirmed the existence of silver nanaoparticles with a peak at 46.253°. The dose dependent cytotoxicity was observed in the aqueous and silver nanoparticles of P.aureum. Conclusion: The present study gave a simple and cheap route to synthesize the AgNPs using aqueous extracts of P. aureum. The studied extracts of P. aureum can be considered as a promising candidate for a plant-derived anti-tumour compound.

Background: Zanthoxylum bungeanum seed oil (ZBSO) is the main extract of the edible drug Zanthoxylum bungeanum seeds. Recent reports have proved that it has a significant cytotoxic effect on various cancer cells. However, systematic investigation on the role of ZBSO in laryngeal carcinoma (LC) is rare. Objective: The aim of the study was to reveal the function of ZBSO on human laryngeal squamous carcinoma cells (Hep-2) and to elucidate its underlying mechanism. Methods: In this study, the chemical composition analysis of ZBSO was done using Ultra Performance Liquid Chromatography (UPLC), and the anti-tumor effect of ZBSO on Hep-2 cells was evaluated by cell proliferation, apoptosis and cell cycle experiments. qRT-PCR, immunohistochemistry (IHC) and Western blotting were used for mechanistic investigation at the molecular level. Results: The main compound of ZBSO was identified as polyunsaturated fatty acids. Furthermore, as compared to normal cells, significant inhibitory activities of ZBSO were observed on Hep-2 cells with dose- and timedependency, which induced apoptosis, blocked cell cycle at the S phase, and inhibited cell proliferation. In addition, IHC results showed a difference in the level of protein expression of ZBSO-induced autophagy-related markers. At last, Western blotting results indicated that ZBSO could inhibit the expression and phosphorylation levels of PI3K/AKT/mTOR protein. Conclusion: The anti-LC effect of ZBSO might be intimately associated with the induction of autophagy and the inhibition of the PI3K/AKT/mTOR signaling pathway. ZBSO may be a potential anti-laryngocarcinoma agent.