Background: Cancer is a major cause of death worldwide. Although modern medicine has made strides in treatment, a complete cure for cancer remains elusive. Summary: Utilization of medicinal plants in traditional medicine for the treatment of multiple diseases, including cancer, is a well-established practice. Sinomenine is an alkaloid extracted from a medicinal plant and has a diverse range of biological properties, including anti-oxidative, anti-inflammatory, and antibacterial effects. Sinomenine exhibits inhibitory effects on various types of tumor cells, including breast, lung, and liver cancers. The anticancer properties of sinomenine are believed to involve stimulation of apoptosis and autophagy as well as suppression of cell proliferation, invasion, and metastasis. Key Message: This review summarizes the current research on sinomenine’s potential as an anticancer agent, which may contribute to the discovery of more effective cancer treatments.

Cancer is a class of malignant tumors characterized by uncontrolled and abnormal growth of cells that cause local accumulation of cells and spread to adjacent tissues and other organs through body fluids [1]. The incidence of cancer continues to rise annually, which poses a significant risk of mortality and adverse quality of life of affected patients and families [2]. The cancer burden has increased with time in industrialized and developing nations owing to a variety of variables, such as aging and growing populations and accelerated growth in socioeconomic status. The socioeconomic patterns of mortality from all cancers, including lung and colorectal cancers, have varied considerably over time. Individuals in less wealthy locations or with low educational and income levels had greater death and incidence rates than those of their more affluent counterparts, with an increased risk of lung, colorectal, cervical, stomach, and liver cancers [3, 4]. However, differences in cancer diagnostic patterns have been observed. Consequently, it is expected that future studies will find that rural populations have lower rates of cancer screening and less effective cancer treatment. Furthermore, multiple studies have found increased rates of cancer-risk behaviors among rural residents, which may contribute to higher incidence rates. The number of newly diagnosed cancer cases exceeds 19.3 million, leading to approximately 10 million fatalities [3]. Although cancer diagnosis and treatment have improved dramatically in recent years, the 5-year survival rates for cancer patients have remained relatively low because of the gradual development of drug resistance in cancer cells and the exorbitant cost of cancer drugs [4]. Clinically used anticancer drugs usually work by inhibiting rapid cell division but unfortunately can kill both cancer and normal cells, leading to serious adverse reactions, such as hair loss, vomiting, and diarrhea [5]. Therefore, economical, safe, and reliable anticancer drugs with fewer side effects are urgently needed.

Medicinal plants and their active components are extensively used in medicine today. The potential of medicinal plants as a source of anticancer compounds has been verified in traditional medicine and through research experiments. Reportedly, 60% of anticancer drugs, such as paclitaxel, vinblastine, and vinca alkaloids, have been discovered from medicinal plants [6]. Sinomenine (C19H23NO4), 8-dihydro-4-hydroxy-3,7-dimethoxy-17-methylmorpholin-6-one (Fig. 1) is an isoquinoline alkaloid first isolated from Sinomenium acutum (Thunb.) Rehder and E.H. Wilson by the Japanese scientist Ishiwari in the 1920s [7]. Previous studies have shown a wide range of biological activities of sinomenine, such as antitumor [8], antioxidant, and anti-inflammatory activities [9]. Numerous preclinical investigations have demonstrated that sinomenine has noteworthy inhibitory properties against diverse cancer types, such as pulmonary, liver, gastrointestinal, breast, pancreatic, cervical, and ovarian tumors. The molecular mechanisms underlying the anticancer properties of sinomenine involve induction of apoptosis [10], inhibition of cell proliferation [11], enhanced reactive oxygen species (ROS) accumulation [12], and induction of autophagy [12], among others, as shown in Figure 2.

Fig. 1.

Chemical structure of sinomenine.

Fig. 1.

Chemical structure of sinomenine.

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Fig. 2.

Molecular mechanisms of sinomenine’s anticancer properties: apoptosis induction, cell proliferation inhibition, ROS accumulation enhancement, and autophagy induction.

Fig. 2.

Molecular mechanisms of sinomenine’s anticancer properties: apoptosis induction, cell proliferation inhibition, ROS accumulation enhancement, and autophagy induction.

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In this review, we present the latest research on the role of sinomenine in the prevention and treatment of diverse forms of tumor cells. We provide an overview of the research on sinomenine antitumor functions and molecular processes and discuss the theoretical basis for the clinical development and application of sinomenine.

Recent studies have highlighted the promising potential of sinomenine as an effective anticancer agent, with oncologists demonstrating its efficacy against tumors through multiple approaches. Sinomenine has a significant inhibitory effect on a variety of malignant tumors and modulates several signaling pathways related to cancer (Table 1).

Table 1.

The anticancer properties of sinomenine

Cancer typeFunction test; modelSinomenine doseResults (cell signaling pathways)References
Breast cancer Murine breast cancer cell lines 4T1; MDA-MB-231 0.25–1 mM Blocking the IL-4/miR-324-5p/CUEDC2 axis inhibits breast cancer cell invasion and migration [13, 14
MCF-7, SK-BR-3, ZR-75–30, BT474, and T47D 0.25–1 mM 
Increased MAPK activity induces cell death in breast cancer via ROS-dependent and -independent mechanisms 
Normal human breast epithelial cell line of MCF-10A 75–150 mg/kg 
Lung cancer Human lung cancer cell line A549, NCI-H460, NCI-H226, and NCI-H522 0.1–4 mM The regulation of the STAT3 signaling pathway inhibits EMT, which in turn inhibits the invasion of lung cancer cells [15, 16
200 μg/mL Multiple lung cancer cell lines were made to undergo apoptosis by activating both the Akt and ERK signaling pathways 
Liver cancer Human hepatocellular carcinoma cell line SMMC-7721 and Hep3B 0.5–2 μg/mL Inducing cell cycle arrest and apoptosis by activating caspase cascade and mitochondrial apoptosis pathway [17
Cervical cancer Human cervical cancer cell Hela 1 mm Activating caspase-3 production and triggering apoptosis in Hela cells by suppression of AKT signal transduction protein expression [18
Ovarian cancer HeyA8 cell 0.25–8 mM Inhibiting the growth of the HeyA8 cells through downregulating the expression and the activity of CDK1 [19
Gastric cancer Human gastric cancer cell line MKN-28, SGC-709, BGC-823, and HGC-27 20 mg/kg 5-Fu+10 mg/kg Reduced TS mRNA expression increases gastric cancer cell susceptibility to 5-Fu through boosting 5-Fu-induced apoptosis via the mitochondrial route [20
Cancer typeFunction test; modelSinomenine doseResults (cell signaling pathways)References
Breast cancer Murine breast cancer cell lines 4T1; MDA-MB-231 0.25–1 mM Blocking the IL-4/miR-324-5p/CUEDC2 axis inhibits breast cancer cell invasion and migration [13, 14
MCF-7, SK-BR-3, ZR-75–30, BT474, and T47D 0.25–1 mM 
Increased MAPK activity induces cell death in breast cancer via ROS-dependent and -independent mechanisms 
Normal human breast epithelial cell line of MCF-10A 75–150 mg/kg 
Lung cancer Human lung cancer cell line A549, NCI-H460, NCI-H226, and NCI-H522 0.1–4 mM The regulation of the STAT3 signaling pathway inhibits EMT, which in turn inhibits the invasion of lung cancer cells [15, 16
200 μg/mL Multiple lung cancer cell lines were made to undergo apoptosis by activating both the Akt and ERK signaling pathways 
Liver cancer Human hepatocellular carcinoma cell line SMMC-7721 and Hep3B 0.5–2 μg/mL Inducing cell cycle arrest and apoptosis by activating caspase cascade and mitochondrial apoptosis pathway [17
Cervical cancer Human cervical cancer cell Hela 1 mm Activating caspase-3 production and triggering apoptosis in Hela cells by suppression of AKT signal transduction protein expression [18
Ovarian cancer HeyA8 cell 0.25–8 mM Inhibiting the growth of the HeyA8 cells through downregulating the expression and the activity of CDK1 [19
Gastric cancer Human gastric cancer cell line MKN-28, SGC-709, BGC-823, and HGC-27 20 mg/kg 5-Fu+10 mg/kg Reduced TS mRNA expression increases gastric cancer cell susceptibility to 5-Fu through boosting 5-Fu-induced apoptosis via the mitochondrial route [20

Breast cancer is the second-most common cause of cancer-related fatalities globally [21]. Numerous studies have demonstrated that sinomenine can prevent the proliferation, invasion, and migration of breast cancer cells. In addition, it has been observed to induce apoptosis and improve the accumulation of ROS, thereby indicating its potent anticancer potential [22]. Studies have suggested that sinomenine exerts its anticancer effects in breast cancer by regulating estrogen receptors, which have a crucial role in hormone receptor-positive breast cancer [23]. Many studies have established that the phosphatidylinositol 3 kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway is dysregulated in different cancer types, leading to abnormal proliferation of tumor cells [24, 25]. Despite the use of rapamycin analogs and other related inhibitors in cancer treatments, resistance and poor prognosis are possible [26]. Therefore, there is a pressing need to identify new, effective, and low-toxicity compounds. Song et al. discovered that sinomenine prevented the proliferation and expansion of MDA-MB-231 SP breast cancer cells. This potential mechanism may be related to the inhibition of PI3K, Akt, and mTOR protein phosphorylation in MDA-MB-231 SP breast cancer cells. Moreover, sinomenine inhibited the synthesis of E-cadherin, N-cadherin, vimentin, and matrix metalloproteinase (MMP)-9, which are involved in epithelial-mesenchymal transformation (EMT) [11]. Another study found that the molecular mechanism underlying sinomenine’s inhibition of invasion and metastasis of breast cancer cells involves upregulation of CUEDC2 gene expression, inhibition of IκB kinase phosphorylation, and downregulation of IL-4 secretion and miR-324-5p expression [27].

MicroRNAs (miRNAs) have a significant effect on the development and progression of breast cancer because they are associated with cell growth and metastasis and have an active role in breast cancer. Reportedly, sinomenine may affect the development of certain miRNAs, such as miR-324-5p, miR-340-5p, and miR-29, in cancer cells. As previously described, sinomenine dose-dependently upregulated CUEDC2 gene expression and decreased miR-324-5p expression in MDA-MB-231 cells, thus inhibiting breast cancer cell invasion and metastasis [13]. Sinomenine suppressed tumor-cell migration and invasion in a study of MDA-MB-231 breast cancer cells by boosting miR-29 expression. Moreover, overexpression of miR-29 was found to enhance caspase-3 and -9 expression, further promoting apoptosis [10]. Sinomenine reportedly also inhibited angiogenesis and migration of MDA-MB-231 SP breast cancer cells by enhancing miR-340-5p expression [28]. These findings show that the anticancer effect of sinomenine involves regulating miRNA expression.

In vivo and in vitro studies have shown that sinomenine inhibits Wnt/β-catenin signaling by reducing WNT10B expression. Sinomenine was shown to reduce the ratio of CD44+/CD24− breast cancer stem cells and the expression of breast cancer stem cell-related genes in MCF-7 and MDA-MB-231 cells. Sinomenine also dramatically reduced the stemness of CD44+/CD24− breast cancer stem cells, including their ability to self-renew, form oncospheres, migrate, invade, and express stemness-related genes. In addition, sinomenine clearly suppressed Wnt signaling pathway gene expression in CD44+/CD24− breast cancer stem cells, particularly WNT10B and its downstream target genes. When WNT10B was overexpressed, the sinomenine regulatory effect of sinomenine on breast cancer stem cell stemness was prevented, demonstrating that sinomenine inhibited breast cancer stem cell stemness by downregulating WNT10B [29]. Sinomenine has been shown to suppress cancer cell growth and cause apoptosis in a variety of tissues, including breast tissues; however, its effects on breast cancer invasion and metastasis have seldom been described. Previously, sinomenine was shown to inhibit proliferation, invasion, and migration in 4T1 mice and MDA-MB-231 human high-metastatic breast cancer cells. The study found that sinomenine inhibited NF-B pathway activation by modulating the IL-4/miR-324/CUEDC2 axis and decreased the invasion and migration of breast cancer cells in vitro [30].

There is a strong correlation between the mitogen-activated protein kinase (MAPK) signaling pathway and development of breast cancer. In addition, sinomenine is therapeutically used as a prognostic indicator [31]. Li et al. [32] confirmed that sinomenine inhibited cell proliferation by promoting G1/S cell cycle arrest, enhancing ROS production, and triggering oxidative DNA damage in breast cancer cells [33]. In addition, Li et al. found that the MAPK pathway has a role in sinomenine-induced cell death in breast cancer through both ROS-dependent and -independent pathways. Specifically, pERK, pJNK, and p38 MAPK were upregulated within the pathway in this process [13].

Commercial IκB kinase (IKK) inhibitors, such as IKK-16, TPCA-1, and Bay 11–7,085, have been used in research and clinical trials [34]. Multiple studies have found that certain inhibitors of IKK2 are toxic to multiple myeloma cells. However, the effects of these inhibitors vary, and recent research suggests that simultaneous inhibition of alternative and classic pathways is necessary to induce cell death in multiple myeloma. Specifically, the inhibitor PBS-1086, which targets the Rel protein, demonstrated this effect. Interestingly, when both IKK1 and IKK2 were simultaneously inhibited, there were no significant short-term adverse effects on the viability of multiple myeloma cells [35]. CUEDC2 is an inhibitor of IKK activation, which helps keep NF-κB inactive, and is achieved by recruiting the phosphatase PP1 and blocking the phosphorylation of IKK. Consequently, CUEDC2 has a significant role in suppressing NF-κB-mediated tumorigenesis and progression [36]. One study discovered that sinomenine, when incubated with MDA-MB-231 and 4T1 breast cancer cell lines, effectively reduced their ability to invade and migrate. This reduction was achieved by inhibiting IKK phosphorylation and NF-κB activation by mediating the upstream IL-4/miR-324-5p/CUEDC2 axis [37]. There have been few clinical trials evaluating the efficacy and safety of sinomenine in patients with breast cancer, so further research is needed to fully understand its potential as a therapeutic agent.

Anticancer Role of Sinomenine in Pulmonary Cancer Proliferation

Presently, lung cancer is the most common form of malignant cancer observed clinically, with 2 million annual diagnoses and 1.76 million fatalities [38]. Despite the use of multimodality medicines and some molecular-targeted therapies, the clinical response to chemotherapy in patients with lung cancer remains inadequate, and the 5-year life expectancy rate in numerous nations is <15% [39]. More effective chemopreventive and therapeutic techniques are required to increase this rate. Growing evidence from in vivo and in vitro studies suggests that sinomenine has anticancer effects on lung cancer. The observed effects include suppression of cellular proliferation, invasion, and metastasis as well as stimulation of cellular apoptosis and cell cycle arrest [40]. In 2010, Jiang et al. [15] reported that sinomenine exhibited dose- and concentration-dependent inhibition of NCI-H460 cell proliferation. Furthermore, Zhou et al. [16] found that sinomenine inhibited NCI-H460 cell growth over time and speculated that this effect is mediated by the considerable activation of pAkt and pERK.

Multiple lines of evidence suggest that failed cancer treatment may be attributed to tumor invasion and metastasis. One hypothesis states that EMT is intrinsically linked to tumor invasion, metastasis, and chemical resistance [41]. Epithelial markers in tumor cells, including β-catenin, E-cadherin, and cytokeratins, are generally downregulated, whereas mesenchymal markers, such as N-cadherin and vimentin, are upregulated [42]. Therefore, effective inhibition of EMT is crucial for successfully treating cancer. Jiang et al. [43] found that sinomenine inhibited cell invasion by reducing EMT biomarker (N-cadherin) protein expression. One hypothesis is that the potential mechanism by which sinomenine inhibits EMT protein expression involves regulating the signal transducer and activator of transcription 3 (STAT3) and its downstream target Snail [43].

Hexokinase 2 (HK2), a hexokinase closely associated with the Warburg effect in tumors, is overexpressed in a variety of human patients with cancer and is positively associated with poor prognosis [44, 45]. Liu et al. [46] demonstrated that sinomenine inhibited cell growth by decreasing AKT activity and downregulating HK2 protein expression. The antitumor outcome of sinomenine was confirmed in HCC827 and H1975 xenograft mouse models.

MMPs are pivotal enzymes that contribute to tumor-cell motility, invasion, and metastasis [47]. In a preclinical study, sinomenine inhibited the expression of extracellular inducers of MMP (the activity of MMPs) and enhanced the expressions of reversion-persuading cysteine-rich proteins with kazal motifs and MMP-1 and -2). Consequently, the expressions of MMP-2 and -9 were suppressed, and human lung cancer invasion and metastasis were slowed [48].

Frequently, cell proliferation and survival are related to activation of the Akt and ERK1/2 pathways. According to research by Zhou et al. [16], sinomenine time-dependently diminished NCI-H460 cell growth, followed by considerable activation of pAkt and pERK. Sinomenine-induced apoptosis was considerably boosted by the LY294002 and PD98059 inhibitors in NCI-H460, NCI-H226, and NCI-H522 cells. Our findings imply that the PI3K/Akt and ERK signaling pathways limit SIN-induced lung cancer cell death and that drugs that inhibit these pathways should enhance the effects of sinomenine [16]. Through the mitochondrial pathway, sinomenine can cause apoptosis by modifying the mitochondrial membrane potential, which in turn causes the release of cytochrome c, activation of caspase-3 and -9, and elevation of Bax levels while simultaneously lowering Bcl-2 levels [16].

The 7-nicotinic acetylcholine receptor (7-nAChR), a receptor of nicotine (a component of tobacco that is known to cause cancer) and its numerous metabolites, can promote cell proliferation and tumorigenesis by mediating the proliferative, proangiogenic, and prometastatic activities of nicotine [49‒51]. Thus, 7-nAChR is considered a latent target for lung cancer treatment. Previous in vitro and in vivo studies have shown that sinomenine efficiently suppresses cell proliferation and migration while simultaneously promoting cell death. One possible molecular mechanism is related to the downregulation of 7-nAChR expression [52].

Liver Cancer

Liver cancer is one of the most frequent cancers worldwide, with a high recurrence and metastasis rate [53]. Hepatic ectomy is now the primary treatment for individuals with early-stage hepatocellular carcinoma (HCC), whereas transarterial chemoembolization (TACE) is chosen for patients with intermediate- and advanced-stage malignancies [54]. However, most standard hepatic artery embolization drugs have drawbacks, such as limited embolic selectivity, partial embolization, and inadequate embolization time [55]. Multiple studies have reported sinomenine’s benefits in HCC [17, 56, 57]. The results of these studies showed the significant anticancer properties of sinomenine against various subtypes of liver cancer. Its anticancer effect was achieved by preventing cancer cell metastasis, increasing DNA damage, and causing cell death by downregulating Blc-2 and upregulating P21 in a concentration-dependent manner [17, 58].

Cyclooxygenase-2 (COX-2), an enzyme related to proliferation and angiogenesis, is overexpressed in various cancer cells. Hong et al. [59] reported that sinomenine dose-dependently downregulated the expressions of COX-2 and VEGF, which promoted apoptosis and cell cycle arrest. That study also found that the combination of sinomenine and anti-transferrin receptor monoclonal antibodies functioned synergistically to inhibit cancer cell propagation and cell apoptosis initiation [59].

Recent research demonstrated that sinomenine promoted apoptosis in SK-Hep-1 HCC cells by dissipating mitochondrial membrane potential and injecting cytochrome C into the cytoplasmic lysate [56]. The potential underlying molecular mechanism is related to the downregulation of PI3K-p85α, AKT1, BCL-2, and procysteine aspartase-9 and -3 as well as to the upregulation of cleaved cysteine aspartase-9 and -3 [56].

Cervical Cancer

Cervical cancer is a growing concern, with increasing incidence rates and a high mortality rate among women with cancer [60]. Radiotherapy is an effective cancer treatment, and several molecular signaling mechanisms, including the DNA-damage-response (DDR), have been linked to radioresistance in cervical cancer [61]. Independent investigations using high-throughput screening have also observed DDR gene-expression pattern alterations in cervical cancer tissues or cell lines resistant to infrared radiation [62]. For example, radioresistant cervical carcinoma has increased nonhomologous end-joining proteins [63], which provides insight into the molecular pathways driving DDR-related radioresistance. Furthermore, current studies have concentrated on the identification, development, and assessment of radiosensitizers for cervical cancer therapy that target DDR components [64].

In an in vitro HeLa cell model, sinomenine sensitized HeLa cells to ionizing radiation and promoted apoptosis [18]. A possible mechanism is that increasing the phosphorylation level of Chk1 S345 and inhibiting the expressions of Ku80 and Rad51 promote the repair of DNA double-strand damage induced by ionizing radiation and prevent activation of the DNA-damage checkpoint [18]. Recent studies have shown that sinomenine acts on the Sec residue of overexpressed thioredoxin reductase, causing a buildup of ROS and disruption of cellular oxidative metabolism, ultimately leading to oxidative stress-induced death in cancer cells [65].

Ovarian cancer is a fatal gynecologic cancer, primarily because it is detected at an advanced stage in most patients. The rapid diffusion of ovarian cancer cells to the peritoneum, omentum, and organs situated in the peritoneal cavity accounts for its aggressiveness [66]. The lncRNA family member, HOST2, is widely expressed in ovarian cancer [67]. Sinomenine has been reported to significantly inhibit the expression of long-chain noncoding RNA HOST2 in a dose-dependent manner, resulting in a decrease in Caov3 and SKOV3 cell viability [68]. Sinomenine also promotes cell apoptosis through G0/G1 phase arrest [68]. Recent work has shown that sinomenine inhibits HeyA8 cell growth by inhibiting mitosis and modulating its expression and activity [19]. Sinomenine inhibits proliferation and metastasis in ovarian cancer cells in a time- and concentration-dependent manner and may inhibit metastasis while reversing EMT and decreasing β-catenin nuclear accumulation. MCM2 regulates β-catenin and ZEB1, an important EMT regulator. These findings are crucial for determining the sinomenine antitumor molecular mechanism in ovarian cancer [69].

Brain Cancer

In the central nervous system, glioblastoma is the most prevalent primary malignancy, representing 45.6% of primary malignant brain cancers [70]. Sirtuin 1 (SIRT1) has a significant role in cell growth and apoptosis within glioma cells [71, 72]. In an in vitro cell model, sinomenine downregulated SIRT1 and induced p53 acetylation, causing G1-phase cell-cycle arrest and apoptosis in U87 and U251 cells [73]. Sinomenine also prevented the production of phosphorylated STAT3, a key regulator of tumor-cell proliferation [74].

Dysfunction of autophagy is associated with tumorigenesis and malignant conversion. Sinomenine inhibits cell growth by inducing ROS generation and activating cellular autophagy, which is coupled with inhibition of the Akt-mTOR pathway and stimulation of the JNK pathway [12]. As shown by clinical and experimental investigations, MMPs have an instrumental role in tumor invasion, metastasis, and neoangiogenesis, and blocking MMP-2 and MMP-9 production is considered a prospective strategy to prevent tumor cells from proliferating [75, 76]. In an in vitro antitumor study, Jiang et al. [77] found that sinomenine could induce cell cycle arrest, inhibit cell invasion and growth, and reverse endogenous and exogenous EMT, leading to reduced cell metastasis by regulating the expressions of MMP-2 and MMP-9.

Colon Cancer

Colon cancer is the third most frequent malignancy [78]. Sinomenine has antitumor effects by downregulating COX-2, which is implicated in various cancers, including colon [59], gastric [79], and liver cancer [80]. In an in vivo study, sinomenine affected the expression of cyclin D1, cyclin E, Cip1/p21, and Kip1/p27, causing G1-phase cell cycle arrest leading to inhibition of cellular development [73].

Bone Cancer

Osteosarcoma is a primary malignant bone tumor that typically occurs during childhood and adolescence. Its clinical presentation is characterized by local pain and swelling [81, 82]. Sinomenine can trigger apoptosis through direct mechanisms, including G1/S cell-cycle arrest. Furthermore, sinomenine reduced VEGF-associated neovascularization and decay of the extracellular matrix with tumor cells by reducing NF-kB ligand-mediated bone destruction and osteolysis in osteosarcoma [83].

Combined administration is a common cancer-treatment strategy that helps overcome drug resistance and reduces cytotoxicity caused by high-dose administration. Therefore, it is not surprising that combinations of sinomenine and other anticancer agents have been investigated in a broad range of cancers. Co-administration of sinomenine and 5-fluorouracil (5-FU) has demonstrated significant inhibition of the proliferation of LoVo cells in colon cancer [84]. In another antitumor study, sinomenine time- and dose-dependently inhibited gastric cancer cell multiplication and acted synergistically with 5-FU. As expected, sinomenine activated the mitochondrial pathway, downregulated the expression of thymidylate synthase mRNA, and improved the susceptibility of gastric cancer cells to 5-FU [20]. Similarly, in esophageal cancer, the combination of sinomenine and 5-FU dramatically inhibited the growth of Eca-109 cells by activating the mitochondrial pathway and regulating apoptosis and anti-apoptosis-induced cell death [14].

In conclusion, sinomenine has shown promise as an antitumor agent for various types of cancer. The information provided in this review should be helpful for advancing the development of this natural compound as a potential drug candidate for clinical cancer treatment. Extensive research has demonstrated the compound’s ability to inhibit tumor growth and metastasis, making it a valuable candidate drug for cancer treatment. The mechanism of action of sinomenine involves suppressing angiogenesis, inducing apoptosis, and modulating immune responses, all of which contribute to its anticancer effects. In addition to its direct effects on cancer cells, sinomenine also modulates the immune system, enhancing its ability to recognize and eliminate cancer cells.

Furthermore, sinomenine exhibits low toxicity and has minimal side effects, making it a favorable option for patients with cancer. Its natural origin from the Chinese medicinal plant S. acutum adds to its appeal as a potential alternative or complementary therapy. The specific mechanisms by which sinomenine exerts its antitumor effects are still being elucidated, providing opportunities for future investigation and potential therapeutic advancements. However, further clinical trials and investigations are necessary to fully understand its efficacy, optimal dosage, and potential interactions with other cancer treatments. Overall, sinomenine holds promise as a novel antitumor medicine that warrants further exploration in clinical oncology.

The authors have no conflicts of interest to declare.

This work was supported by grants from the National Natural Science Foundation of China (NO. 81870935) and the Scientific Research Foundation of Wuhan University of Technology (NO. 40122070) to W.J.

Panzhen Jiang drafted the manuscript and revised it before the final submission. Aqeela Zahra polished the grammar of the article. Xi Guo improved the charts and formatting of the article. Jianping Wu critically revised the manuscript.

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