Danshen Evidence And Its Impact On Cancer Treatment: Danshen Cancer Evidence

DANSHEN

Danshen is a form of salvia from the mint family, and the leading chinese herbal medicine added to standard western oncology in asia. In Tiawan, about a third of patients routinely include danshen alongside their oncology treatments. The National health insurance database there has been widely used to analyze outcomes of various cancer types based on prescription use during and after treatment. These large scale long term studies report clear evidence of significantly improved patient outcomes in advanced stage breast, lung, prostate, colorectal and bladder cancers with chemotherapy or tyrosine kinase inhibitors. The reduction in real world risk reductions compare strikingly well with the addition of second ot third oncology drugs such as eimmunotherapy or anti-angiogenisys class medications which are often unable to improve patient outcomes ( see Examples).

Used as a supporting therapy to both chemotherapy and tyrosine kinase inhibitors, results range from 10 – 20% reduced relative risk in prostate cancer, up to 50% lowered risk in advanced lung and breast cancers both HER+ and HER- types. The dataset is from large groups of patients followed over a 10 year period. For maximum effect, sustained use of 3 x 1g daily for more than 3 months showed strong results than shorter usage.

Clinical trials have reported on patients adding traditional chinese medicine to oncology treatments. Mostly danshen, secondly astragalus. There is some evidence here of much improved response rates in leukemia and liver cancers. The strong suppressive effects in colorectal cancer have research linking the outcomes to the so called SKP2 pathway, which is found upregulated elsewhere particularly kidney and various hematological cancers. Direct evidence for danshens anti-metastatic activity is partly from the reduced progression risk data in patient case records, supported by strong pre-clinical testing of detailed mechanisms.

Active compounds including Tanshinone IIA has been shown to have immune system re-balancing effects, playing a significant role in the development and function of immune cells and reducing inflammatory markers., helping re-regulate both innate and acquired immune responses. Danshen is commonly used to reduce oncology treatment side effects. And outside of cancer for cardivascular and metabolic health including non-alcoholic fatty liver disease, blood pressure management, and management of glucose/ insulin levels in relation to diabetes.

TYPICAL ABSORPTION LEVELS

10 -20%

EXAMPLES OF IMPROVED OUTCOMES

YES

PRE-DIAGNOSIS OR PREVENTION

PENDING

Highlighted Studies

In this study, we excluded [breast cancer] patients who did receive taxane to ensure that the patients in our cohort had stage III–IV disease…..After 10 years, survival rate analysis demonstrated a strong association between the use of danshen and survival … the use of danshen ≥84 g [>28 days at 3g daily doses] was highly associated with decreased mortality (the adjusted HR of danshen ≥84 g users was 0.54….Moreover, the use of danshen for >28 days remained highly...

We included a total of 60,267 patients (20,645 women and 39,622 men) diagnosed with late stage of lung cancer during the study period …. analysis demonstrated a strong association between the use of danshen and a decrease in mortality. Compared with danshen nonusers or used < 30 g, danshen users who had used ≥ 90 g had reduced mortality by 58.4%. The group who had used < 90 g and ≥ 30 g of danshen had reduced mortality by 63.7%…Collecting together, this is a novel model ...

Patients [prostate cancer] were also categorized into three groups according to the duration of their drug use: those who had never used danshen and those who had used danshen for either > 28 or ≤ 28 days after their prostate cancer diagnosis, as per medical records. After 15 years of follow-up, the survival rate analyses demonstrated a strong dose-dependent and time-dependent association between the use of danshen and survival.. Notably, danshen users exhibited an increase of 5%–10% i...

The studies investigated the lung cancer (n = 5), leukemia (n = 3), liver cancer (n = 3), breast or colon cancer (n = 1), and gastric cancer (n = 1)…. Meta-analysis suggested that Danshen formulae had a significant effect on RR (response rate) (OR 2.38), 1-year survival (OR 1.70), 3-year survival (OR 2.78), and 5-year survival (OR 8.45). Conclusion. The current research results showed that Danshen formulae combined with chemotherapy for cancer treatment was better than conventional drug...

TABLE OF REFERENCES

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836808/	5	After 10 years, survival rate analysis demonstrated a strong association between the use of danshen and survival... the use of danshen ≥84 g was highly associated with decreased mortality ...Moreover, the use of danshen for >28 days remained highly associated with decreased mortality... Thus, these data demonstrate the protective effects of a higher dose or longer use of danshen for patients with breast cancer in Taiwan.	After 2 weeks of DT treatment (30 mg/kg, IP), there was no significant alteration in either the activity or the body weight of the mice, and no mice died (Figure 6A). Moreover, we discovered that DT treatment (30 mg/kg, IP) significantly limited the final tumor volume, by approximately 70%, after 2 weeks (Figure 6B). These results suggested that DT treatment induced only limited adverse events in mice, validating our data from the cell lines.	After treatment with the indicated compounds for 24 to 48 h, 5–10 μM DT significantly inhibited the proliferation of both MCF-7 cells and MDA-MB-231 cells in a dose-dependent and time-dependent manner (Figures 3B, C). In addition, DT had a better inhibitory effect than 5–10 μM SA. Notably, 10 μM DT exhibited a stronger inhibitory effect than 10 μM oxaliplatin, gemcitabine, and 5-fluorouracil, commonly used anti-breast cancer clinical agents. Moreover, DT exerted a pronounced inhibitory effect on the proliferation of MCF-7 cells, even at the lowest concentration (5 μM). These data suggest that DT has a role in the growth inhibition of human breast cancer cells.
https://www.oncotarget.com/article/14958/text/	5	In summary, this is a novel study that demonstrated how DT can inhibit the migratory ability of the prostate cancer cells and the macrophage recruitment ability of the prostate cancer cells. These results suggest that DT is a novel anticancer agent in the armamentarium of prostate cancer management.	After 15 years of follow-up, the survival rate analyses demonstrated a strong dose-dependent and time-dependent association between the use of danshen and survival (Figure (Figure1).1). Notably, danshen users exhibited an increase of 5%–10% in the survival rate compared with danshen nonusers. Thus, these data demonstrated the protective effects for danshen for prostate cancer patients	Considerable evidence also indicates that macrophages are cultured by the tumor microenvironment to promote metastasis through the production of several compounds, including cytokines [44]. In the present study, we investigated the direct effect of DT on the migratory ability of prostate cancer (Figure (Figure2).2). We also examined the effect of cytokines from the conditioned medium of THP-1 cells, treated with DMSO or DT, on the migratory ability of prostate cancer cells..Notably, no cytokines from the THP-1 cells were observed in the medium depicted in Figure Figure22.
https://www.oncotarget.com/article/18767/text/#	5	Collecting together, this is a novel model demonstrating that danshen has protective efforts for the advanced lung cancers patients in Taiwan through the data of NHIRD. DT inhibit the migratory ability and the macrophage recruitment ability of lung cancer cells from the in vitro study. DT might be a novel anti-lung cancer agent and further prospective randomized study is warranted to validate this finding.	Our results revealed that 5 μM DT significantly inhibited the migration ability of A549 cells in the THP-1 cell medium (Figure 3J). After adding 5 pg/mL of CCL2 to the conditioned medium, we observed that CCL2 partially rescued the migration ability of DT-treated A549 cells (relative migration: from 25% to 60%). The human cytokine array showed that DT treatment can inhibit both CCL2 and CXCL1 expression (Figure 3A). Previous studies have reported CXCL1 as an important cytokine in lung cancer development [36, 37]. Our results suggested that CCL2 is one of the critical cytokines that control the migration ability of DT-treated lung cancer cells	Studies have reported that STAT3 interacts with the Skp2 pathway to regulate the motility and invasion of cancer cells [45, 65]. Skp2 is a vital protein in lung cancer metastasis and proliferation [46–48]. More important, previous studies showed down-regulation of Skp2 can induces apoptosis in lung cancer cells [66]. Skp2 also could control p53/p300 pathway to control apoptosis [67]. In recent study, LINC473 play the critical role for lung cancer growth [38]. In our result, we discovered 10 μM DT can inhibit the mRNA expression of Skp2 and LINC473 in A549 cells through mRNA array and qPCR
https://onlinelibrary.wiley.com/doi/10.1155/2019/2310639	5	Meta-analysis suggested that Danshen formulae had a significant effect on RR (response rate) (OR 2.38, 95% CI 1.66-3.42), 1-year survival (OR 1.70 95% CI 1.22-2.36), 3-year survival (OR 2.78, 95% CI 1.62-4.78), and 5-year survival (OR 8.45, 95% CI 2.53-28.27). Conclusion. The current research results showed that Danshen formulae combined with chemotherapy for cancer treatment was better than conventional drug treatment plan alone.	Ten studies [8, 10–12, 14–19] analyzed RR, indicating the RR of the experimental group was higher than that of the control group (OR 2.38, 95% CI 1.66-3.42) (Figure 2). Heterogeneity test P = 0.21, I2 = 25% showed 13 included articles with no heterogeneity, so the statistical analysis with fixed effects model. Pooled OR with 95% CIs showed Z = 4.71, P<0.00001 (Figure 2), suggesting that the difference was statistically significant. It can be considered that the RR of Danshen formulae with the general treatment regimen was higher to the control scheme without the Danshen formulae	It should be mentioned that the current meta-analysis is the first systematic review of the application of Danshen formulae in cancer-assisted treatment. The current meta-analysis found that Danshen formulae can improve the clinical efficiency in cancer treatment. After the addition of Danshen formulae, RR and survival rates were significantly improved. However, it is not clear which components of Danshen formulae have anticancer effects during the treatment, and what role Danshen root plays, which should be the goal of further research
https://www.sciencedirect.com/science/article/abs/pii/S0378874117317725?via%3Dihub	5	Danshen has protective effects in colon cancer patients, which could be attributed to DT through blocking the proliferation of colon cancer cells through apoptosis	we found that dihydroisotanshinone I (DT), a bioactive compound present in danshen, can inhibit the proliferation of colon carcinoma cells, HCT 116 cells and HT-29 cells. Moreover, DT induced apoptosis of colorectal cancer cells.	Danshen improves survival of patients with colon cancer and dihydroisotanshinone I inhibit the proliferation of colon cancer cells via apoptosis and skp2 signaling pathwa
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1260683/full	4	The overall incidence of MACEs [major adverse cardiovascular events] was significantly lower in the Danshen group (5%) compared to the TCM (8.1%) and non-TCM (9.9%) groups ....bladder cancer patients treated with Danshen had the lowest risk of MACE (adjusted hazard ratio, 0.56) and all-cause mortality (adjusted hazard ratio, 0.60)	The Danshen group had the lowest overall mortality rate (8.0%), whereas the non-TCM group had the highest mortality rate (14.6%). During the first hospitalization, the TCM group had the lowest rate (68.1%), followed by the Danshen group (70.1%). During the first hospitalization, the patients in the Danshen group had the longest length of stay (9.9 months) compared with those in the non-TCM (2.7 months) and TCM (6.5 months) groups. No significant differences were noted between patients from different geographic regions.	In this study, we found that Danshen use was associated with a 40% decrease in mortality and a 44% reduction in MACE compared with those in the TCM and non-TCM groups. Compared to previous studies on Danshen’s effects on cardiovascular outcomes in cancer patients, our findings provide a more comprehensive understanding, especially in the context of bladder cancer. Patients with bladder cancer treated with Danshen showed a significantly lower incidence of MACE and improved survival rates. A meta-analysis of 20 randomized controlled trials including 2,574 patients with coronary heart disease showed that Danshen decreased the MACE risk ratio by 47%
https://pmc.ncbi.nlm.nih.gov/articles/PMC5739127/	4	...this study provides real-world data regarding the benefit AML patients may have from CHM [Chinese herbal medicines including danshen and astragalus). This study suggests that all AML patients, regardless of age or other prognostic factors, may achieve longer survival times when receiving CHM in addition to standard therapy	It is shown that patients who took CHM for 30 to 89 days had a HR of 0.39 (95% CI = 0.29-0.52, P < .001) compared with patients from the non-CHM group; patients who took CHM for 90 to 179 days had a HR of 0.30 [Hazard Ration], and patients who took CHM for more than 180 days had a HR of 0.13	Our most significant finding was that the use of CHM was associated with a significant decrease in HR. Patients from the CHM group had a 49% lower HR than that of the non-CHM group. Moreover, it was shown that patients who took CHM for longer periods of time experienced a more substantial decrease in HR
https://europepmc.org/article/med/35600860	2	Breast cancer is one of the most deadly malignancies in women worldwide. Salvia miltiorrhiza, a perennial plant that belongs to the genus Salvia, has long been used in the management of cardiovascular and cerebrovascular diseases. The main anti-breast cancer constituents in S. miltiorrhiza are liposoluble tanshinones including dihydrotanshinone I, tanshinone I, tanshinone IIA, and cryptotanshinone, and water-soluble phenolic acids represented by salvianolic acid A, salvianolic acid B, salvianolic acid C, and rosmarinic acid. These active components have potent efficacy on breast cancer in vitro and in vivo. The mechanisms mainly include induction of apoptosis, autophagy and cell cycle arrest, anti-metastasis, formation of cancer stem cells, and potentiation of antitumor immunity	As one of the main effective ingredients of S. miltiorrhiza, DHT has been extensively studied due to its anticancer, anti-inflammatory, cardioprotective, and other pharmacological activities...DHT [from Danshen] has been reported to induce apoptosis and G1-phase cell cycle arrest in breast adenocarcinoma..DHT restrained the migration and clonogenicity of highly invasive TNBC cells by inhibiting the transformation of epithelial cells into mesenchymal cells... Estrogen receptor (ER) p57 is a thiol oxidoreductase that catalyzes protein folding in the endoplasmic reticulum. DHT, as an ERp57 inhibitor, induced endoplasmic reticulum stress, triggering unfolded protein response activation and apoptosis of MDA-MB-231 cells	Until now, the clinical efficacy of these active ingredients compared with clinical drugs has not been reported yet, but they showed a therapeutic effect on tumor resistance, the reduction of side effects, and the optimization of dosage form for breast cancer treatment. At the same time, it is inevitable to find components like paclitaxel in plants such as S. miltiorrhiza that have significant therapeutic effects on breast cancer. Fortunately, Tan IIA was reported to be more effective than tamoxifen, which is the first-line drug for breast cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714145/	1	Besides, the drug metabolism, pharmacokinetics and pharmacodynamics of Tan I and other potential mechanisms involved in its anti‐tumour in vivo effects needed further elucidation. In summary, Tan I was efficacious in suppressing OS cell growth and metastasis both in vitro and in vivo. Tan I induced cell apoptosis by activating Bax and inhibited tumour proliferation and metastasis by inactivating the JAK‐STAT3 signalling pathway. Therefore, Tan I could be considered and further investigated as a novel, efficient and safe drug candidate for the treatment of OS progression.	In the present study, Tan I suppressed the mRNA and protein expression of MMP‐2 and MMP‐9, possibly responsible for OS cell invasion and metastasis (Figure (Figure5B,C).5B,C). Inflammatory cytokines and signalling pathways are well known to play pivotal roles in enhancing tumour metastasis and drug resistance.53, 54 IL‐6 secreted in the tumour microenvironment activates the JAK/STAT3 signalling pathway, favouring tumour growth and metastasis.55, 56 In determining the potential mechanism, we found that Tan I blocked IL‐6‐induced JAK1/2 and STAT3 activation and down‐regulated p‐JAK1/2 and STAT3 protein levels	Because local or distant recurrences in OS patients involve approximately 90% lung metastases with very poor prognosis,2 it is vital to develop novel efficacious metastasis inhibiting drugs, especially those against OS. Tan I was reported to significantly inhibit lung tumour vascularity and metastasis,33 which we investigated using a metastasis model, and found that Tan I decreased tumour metastasis and significantly increased survival time of mice (Figure (Figure4D,F).4D,F). These results are exciting because the effects of tanshinones on tumour metastases have rarely been reported, although tanshinone IIA has been widely shown to inhibit OS cell growth in vitro and in vivo.21, 50 We therefore concluded that Tan I can effectively suppress OS growth and metastasis in mice.
https://www.sciencedirect.com/science/article/pii/S075333222100370X#	1	DT also induced apoptosis and ferroptosis in these lung cancer cells. DT also blocking the protein expression of GPX4 (Glutathione peroxidase 4). For in vivo study, DT treatment can inhibit metastasis of A549 cells in the nude mice model without adverse effects on mice. In conclusion, DT inhibited the growth of lung cancer cells through apoptosis and ferroptosis and inhibited metastasis of A549 cells in the nude mice model	In the current study, we observed that DT inhibited metastasis of A549 cells in a nude mouse model. Moreover, ferroptosis was significantly associated with the antitumor effect of DT in lung cancer. The similar structure of DT and tanshinone I indicate that ferroptosis may also play a key role in the antitumor effect in other members of the tanshinone family. In summary, at 20–30 μM, DT could inhibit lung cancer cell proliferation through apoptosis and ferroptosis. Thus, DT may be usable as a novel therapeutic agent against lung cancer	Erastin and sorafenib can induce cisplatin-resistant non–small-cell lung carcinoma cell ferroptosis through inhibition of the Nrf2 pathway [30]. Erastin can also downregulate radio-resistance in non–small-cell lung carcinoma cells by inducing GPX4-mediated ferroptosis [31]. Furthermore, acetaminophen may sensitize erastin-induced ferroptosis in non–small-cell lung carcinoma, and erastin and acetaminophen have a synergistic therapeutic effect on lung cancer [32]. Our results demonstrate that DT can induce ferroptosis in lung cancer cells. This finding is promising for the development of a new therapeutic strategy for non–small-cell lung carcinoma, in which erastin and DT are synergized for ferroptosis induction.
https://www.spandidos-publications.com/10.3892/etm.2021.10226	1	he present study also investigated the possible effects of salvianolate on lung adenocarcinoma in vivo using nude mouse xenograft models injected with the A549 cell line. The data revealed that salvianolate not only suppressed lung adenocarcinoma tumor growth of in nude mice, but also downregulated the expression levels of ATP7A and ATP7B, which are important proteins in the tumorigenesis and chemotherapy of lung adenocarcinoma. The present study provided evidence for the potential use of Salvia miltiorrhiza extract for treating lung adenocarcinomas in the clinic.	the present study revealed the DEGs and underlying pathways in lung adenocarcinoma following treatment with different doses of Tanshinone I using bioinformatics tools. In addition, the present study also verified the antitumor effects of salvianolate, another active ingredient of Salvia miltiorrhiza, in animals and lung adenocarcinoma cells. These findings suggest the potential value of applying the Salvia miltiorrhiza extract for lung adenocarcinoma treatment.	The present study downloaded the GSE9315 dataset from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) and the underlying signaling pathways involved after Tanshinone I administration in the lung adenocarcinoma cell line CL1‑5. The results revealed that there were 28 and 102 DEGs in the low dosage group (0.01 and 0.10 µg/ml Tanshinone I) and medium dosage groups (1 and 10 µg/ml Tanshinone I), respectively. In the low dosage group, DEGs were mainly enriched in ‘positive regulation of T‑helper cell differentiation’ and ‘protein complex’
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554091/	1	We found that CT inhibited the proliferation, migration, and invasion of OVCAR3 and HEY A8 cells, while sensitizing the cell responses to the chemotherapy drugs paclitaxel and cisplatin. CT also suppressed ovarian tumor growth and metastasis in immunocompromised mice orthotopically inoculated with HEY A8 cells. Mechanistically, CT degraded the protein encoded by the oncogene c-Myc by promoting its ubiquitination and disrupting the interaction with its partner protein Max.	When we examined tumor metastasis in this animal model, we found that treatment with CT significantly inhibited tumor metastasis in multiple peritoneal organs including the liver, relative to vehicle-treated mice (Figures 8E,F). These results demonstrated that CT suppressed primary ovarian tumor growth and metastasis by inhibiting c-Myc and FAK.	CT as a natural compound with demonstrated antitumor activity in a variety of cancers. In this study, we demonstrated for the first time that CT inhibits HEY A8 ovarian tumor growth and metastasis in an orthotopic mouse model. In particular, we defined a novel molecular mechanism underlying CT’s antitumor activity by demonstrating degradation of c-Myc through ubiquitination. We found that CT also attenuated FAK signaling at an early time point and inhibited FAK activities at a later time point
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3638627/	1	T1 significantly reduces lung adenocarcinoma tumor growth. This result may be due to an effect of T1 on the cell cycle and its pathways. This is the first study to demonstrate that T1 inhibits pulmonary tumor formation in animal model through down-regulation of cell cycle at S and G2/M phases. Our research demonstrated that T1 is an efficacious drug candidate for developing a novel class of antipulmonary cancer drugs.	This reduction in VEGF overexpression has an impact on vasculogenesis and angiogenesis and is a vital factor in tumor formation, growth, invasion, and metastasis. Nizamutdinova and his colleagues [36] have shown that T1 effectively inhibited TNF-α-induced VEGF production and VEGF-mediated tumor formation. In this study, we also found that treatment with T1 effectively decreased the expression of VEGF, thus demonstrating its utility as an antiangiogenic agent for the treatment of pulmonary cancer.	Interestingly, the treatment with T1 (1 mg/kg b.w.) significantly blocked VEGF overexpression in Clara cells when compared to the Tg/CM/Placebo group. These results indicate that T1 can reduce hVEGF overexpression, which could in turn eliminate the formation and growth of new blood vessels. This is a possible explanation for how T1 can effectively block tumor growth, invasion, and metastases.
https://atm.amegroups.org/article/view/54407/html	1	This study showed that Tan-IIA significantly, dose-dependently reduced VEGF and COX2 protein expression in ovarian cancer cells. In our tumor mouse model, Tan-IIA inhibited tumor vessel density by down-regulating VEGF protein expression. In summary, this study provides robust evidence to support the antitumor effect of Tan-IIA in ovarian cancer. In vitro and in vivo experiments showed that Tan-IIA arrested the G2/M phase cell cycle, induced cell apoptosis, and inhibited cell migration and tumor angiogenesis. The results showed Tan-IIA to be a potential anticancer agent for ovarian cancer therapy.	Tanshinone IIA (Tan-IIA) has shown anti-cancer activity in various cancers. In this study, we explored the biological function and mechanisms of Tan-IIA in ovarian cancer. We demonstrated that Tan-IIA effectively inhibited the proliferation and migration abilities of A2780 and ID-8 cells, and induced A2780 and ID-8 cell apoptosis. Additionally, Tan-IIA significantly inhibited tumor growth by tumor angiogenesis in vivo by down-regulating VEGF and COX2 expression. Previous studies have shown that Tan-IIA can inhibit the proliferation of tumor cells, including malignant astrocytoma (20), non-small cell lung cancer (NSCLC) (21), colorectal cancer (22), and gastric cancer (23).	Previous studies have also shown that Tan-IIA suppresses the migration of cervix carcinoma stem cells by inhibiting the transcriptional activity of yes-associated protein (29), inhibits gastric cancer cell migration by downregulating FOXM1 (23), and inhibits human colon cancer cell migration by downregulating the expressions of mTOR protein and VEGF mRNA (14). We disclosed a new mechanism of Tan-IIA in ovarian cancer, in which it has an inhibitive effect on cell migration.
https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-017-2063-y	1	These findings suggest that the Danshen extract induces cell cycle G0/G1 arrest and apoptosis. Resistance to chemotherapy and molecular-targeted therapies is a major concern in current cancer research. Our results reveal that the Danshen extract suppressed growth in drug-resistant oral cancer cells (including taxol, vincristine, and camptothecin resistant cells). These results suggest that the Danshen extract may be a potential novel chemotherapeutic agent in oral cancer treatment.	Many studies have reported that chemotherapeutic drugs exert antitumor effects by triggering apoptosis through various molecular mechanisms. One previous study revealed that tanshinone IIA induces apoptosis in human oral cancer KB cells through a mitochondria-dependent pathway . Our results demonstrate that the Danshen extract upregulated caspase-3 expression and repressed XIAP expression in SAS cells. In addition, our results confirm the involvement of apoptosis in Danshen-induced in vitro and in vivo growth inhibition in human oral cancer cells	However, inflammation, neutropenia and lymphopenia, which are common chemotherapy-induced toxicities, may influence the prognosis of adjuvant chemotherapy in cancer treatment ...Danshen is a natural compound that has anti-inflammation and anticancer effects, which can be effective for the supportive care of cancer patients. Some clinical studies have indicated that bioactive natural compounds play a key role in the treatment of many cancers. In the present study, a Danshen extract was observed to inhibit oral cancer cell proliferation